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CompletedNCT04832971ARCHES-2Updated Dec 3, 2025Results posted

Study of ARO-ANG3 in Adults With Mixed Dyslipidemia

A Phase 2 interventional study of ARO-ANG3 and Placebo in Mixed Dyslipidemia, sponsored by Arrowhead Pharmaceuticals. Completed at 24 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-03.

Sponsored by Arrowhead Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
204
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.

02

Conditions studied

  • Mixed Dyslipidemia
03

In context

Lead sponsor

Arrowhead Pharmaceuticals is the lead sponsor of 50 studies on the registry; 10 are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 12 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Based on medical history, evidence of triglycerides (TG) ≥ 150 mg/dL but ≤ 499 mg/dL
  • Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
  • Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
  • Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care
  • Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication
  • Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
  • Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
  • Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
  • Able and willing to provide written informed consent and to comply with study requirements

Exclusion criteria

Exclusion Criteria:

  • Current use or use within 365 days from Day 1 of any hepatocyte targeted siRNA or antisense oligonucleotide molecule
  • Active pancreatitis within 12 weeks prior to Day 1
  • Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study
  • Acute coronary syndrome event within 24 weeks of Day 1
  • Major surgery within 12 weeks of Day 1 or planned surgery during the study
  • Planned coronary intervention (e.g., stent placement or heart bypass) during the study
  • Uncontrolled hypertension
  • Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV)
  • Uncontrolled hypothyroidism or hyperthyroidism
  • Hemorrhagic stroke within 24 weeks of Day 1
  • History of bleeding diathesis or coagulopathy
  • Current diagnosis of nephrotic syndrome
  • Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study
  • Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply)

Note: additional inclusion/exclusion criteria may apply per protocol

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
204 participants (actual)

Study arms

  • Experimental
    ARO-ANG3 50 mg

    Two doses of ARO-ANG3 by subcutaneous (sc) injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

    Drug: ARO-ANG3

  • Experimental
    ARO-ANG3 100 mg

    Two doses of ARO-ANG3 bysc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

    Drug: ARO-ANG3

  • Experimental
    ARO-ANG3 200 mg

    Two doses of ARO-ANG3 by sc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

    Drug: ARO-ANG3

  • Placebo comparator
    Placebo

    Calculated volume to match active treatment by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

    Drug: ARO-ANG3 · Drug: Placebo

Interventions

  • DrugARO-ANG3

    ARO-ANG3 Injection

  • DrugPlacebo

    Sterile Normal Saline (0.9% NaCl)

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline in Fasting TG at Week 24

    Time frame: Baseline, Week 24

Secondary outcomes

  1. Percent Change From Baseline in Fasting TG Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  2. Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24

    Time frame: Baseline, Week 24

  3. Percent Change From Baseline in Fasting Non-HDL-C Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  4. Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24

    Time frame: Baseline, Week 24

  5. Percent Change From Baseline in Fasting Total ApoB Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  6. Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24

    Time frame: Baseline, Week 24

  7. Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  8. Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24

    Time frame: Baseline, Week 24

  9. Percent Change From Baseline in ANGPTL3 Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  10. Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24

    Time frame: Baseline, Week 24

  11. Percent Change From Baseline in Fasting HDL-C Over Time

    Time frame: Baseline, up to Week 36 (double-blind treatment period)

  12. Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period

    Time frame: Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period)

  13. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24

    TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction.

    Time frame: From first dose of IP up to Week 24

  14. Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period

    Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

    Time frame: up to Week 36 (double-blind treatment period)

  15. Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period

    Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

    Time frame: From first dose of study drug in the OLE up to Month 24 (open-label extension)

  16. Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

  17. Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

  18. Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

  19. Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

  20. Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

  21. Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period

    Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

07

Results

Posted Jan 16, 2024

Participant flow

Double-Blind (DB) Treatment Period
Participant flow — Double-Blind (DB) Treatment Period
MilestonePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgPlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Started51515151000000
Completed48464750000000
Not completed3541000000
Withdrew: Death1000000000
Withdrew: Lost to follow-up1110000000
Withdrew: Withdrawal by subject1331000000
Withdrew: Other, not specified0100000000
Open-Label Extension (OLE) Period
Participant flow — Open-Label Extension (OLE) Period
MilestonePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgPlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Started0000133614391341
Completed0000517314617
Not completed00008191125724
Withdrew: Adverse event0000002111
Withdrew: Death0000000100
Withdrew: Lost to follow-up0000001100
Withdrew: Study terminated by sponsor0000718719419
Withdrew: Withdrawal by subject0000110223
Withdrew: Other, not specified0000001101

Outcome measures

PrimaryPercent Change From Baseline in Fasting TG at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting TG at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Fasting TG at Week 247.55 ± 3.774-43.67 ± 3.770-49.01 ± 3.777-55.57 ± 3.726
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Models Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -51.22 · 95% CI -61.73 to -40.70ARO-ANG3 - Placebo
  • Placebo vs ARO-ANG3 50 mg · Holm method · p = <.0001 (The adjusted p-value is calculated using the Holm method for multiplicity adjustment.)
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -56.56 · 95% CI -67.09 to -46.04ARO-ANG3 - Placebo
  • Placebo vs ARO-ANG3 100 mg · Holm method · p = <.0001 (The adjusted p-value is calculated using the Holm method for multiplicity adjustment.)
  • Placebo vs ARO-ANG3 200 mg · Mixed Model with Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -63.11 · 95% CI -73.56 to -52.66
  • Placebo vs ARO-ANG3 200 mg · Holm method · p = <.0001 (The adjusted p-value is calculated using the Holm method for multiplicity adjustment.)
SecondaryPercent Change From Baseline in Fasting TG Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting TG Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 47.00 ± 3.583-41.52 ± 3.604-52.22 ± 3.658-56.21 ± 3.619
Week 813.58 ± 4.188-41.01 ± 4.217-47.73 ± 4.250-52.55 ± 4.257
Week 122.17 ± 4.305-42.79 ± 4.269-41.71 ± 4.274-49.84 ± 4.183
Week 1617.18 ± 6.952-48.48 ± 6.947-51.99 ± 6.942-58.73 ± 6.820
Week 2011.54 ± 5.930-48.70 ± 5.928-52.73 ± 5.942-57.97 ± 5.790
Week 247.55 ± 3.774-43.67 ± 3.770-49.01 ± 3.777-55.57 ± 3.726
Week 287.24 ± 3.950-41.38 ± 3.966-43.95 ± 4.039-54.39 ± 3.920
Week 36-0.43 ± 3.798-34.49 ± 3.809-38.33 ± 3.850-51.63 ± 3.750
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -48.52 · 95% CI -58.53 to -38.51
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -59.21 · 95% CI -69.30 to -49.12
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -63.21 · 95% CI -73.24 to -53.18
  • Placebo vs ARO-ANG3 50 mg · m · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -54.60 · 95% CI -66.31 to -42.89
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -61.31 · 95% CI -73.07 to -49.55
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -66.13 · 95% CI -77.90 to -54.37
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -44.96 · 95% CI -56.91 to -33.01
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -43.87 · 95% CI -55.83 to -31.92
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -52.00 · 95% CI -63.83 to -40.18
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -65.66 · 95% CI -85.04 to -46.29
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -69.17 · 95% CI -88.54 to -49.80
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -75.91 · 95% CI -95.11 to -56.71
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -60.24 · 95% CI -76.78 to -43.71
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -64.27 · 95% CI -80.83 to -47.72
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -69.52 · 95% CI -85.85 to -53.18
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -51.22 · 95% CI -61.73 to -40.70
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -56.56 · 95% CI -67.09 to -46.04
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -63.11 · 95% CI -73.56 to -52.66
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -48.62 · 95% CI -59.66 to -37.59
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -51.19 · 95% CI -62.32 to -40.05
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -61.63 · 95% CI -72.60 to -50.67
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -34.06 · 95% CI -44.65 to -23.46
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -37.90 · 95% CI -48.56 to -27.25
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -51.19 · 95% CI -61.71 to -40.68
SecondaryPercent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 244.2 ± 3.31-25.1 ± 3.31-24.6 ± 3.31-32.2 ± 3.26
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -29.2 · 95% CI -38.5 to -20.0
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -28.7 · 95% CI -37.9 to -19.5
  • Placebo vs ARO-ANG3 200 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -36.4 · 95% CI -45.5 to -27.2
SecondaryPercent Change From Baseline in Fasting Non-HDL-C Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Non-HDL-C Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 45.2 ± 2.51-23.5 ± 2.52-25.3 ± 2.55-32.9 ± 2.50
Week 83.7 ± 3.02-24.4 ± 3.04-22.8 ± 3.04-30.3 ± 3.02
Week 123.4 ± 3.06-22.8 ± 3.04-18.4 ± 3.04-28.1 ± 2.97
Week 162.5 ± 2.86-26.8 ± 2.86-28.3 ± 2.85-37.0 ± 2.81
Week 200.8 ± 2.71-28.1 ± 2.70-26.5 ± 2.69-34.1 ± 2.64
Week 244.2 ± 3.31-25.1 ± 3.31-24.6 ± 3.31-32.2 ± 3.26
Week 281.2 ± 3.00-23.1 ± 3.01-22.3 ± 3.04-30.0 ± 2.96
Week 36-1.5 ± 3.19-20.2 ± 3.21-17.3 ± 3.23-24.1 ± 3.14
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -28.7 · 95% CI -35.7 to -21.7
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -30.5 · 95% CI -37.5 to -23.4
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -38.1 · 95% CI -45.1 to -31.2
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -28.2 · 95% CI -36.6 to -19.7
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -26.6 · 95% CI -35.0 to -18.1
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -34.0 · 95% CI -42.4 to -25.6
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -26.1 · 95% CI -34.6 to -17.6
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -21.8 · 95% CI -30.3 to -13.3
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -31.5 · 95% CI -39.9 to -23.1
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -29.3 · 95% CI -37.3 to -21.4
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -30.8 · 95% CI -38.8 to -22.9
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -39.5 · 95% CI -47.4 to -31.6
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -28.9 · 95% CI -36.4 to -21.4
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -27.2 · 95% CI -34.8 to -19.7
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -34.8 · 95% CI -42.3 to -27.4
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -29.2 · 95% CI -38.5 to -20.0
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -28.7 · 95% CI -37.9 to -19.5
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -36.4 · 95% CI -45.5 to -27.2
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -24.3 · 95% CI -32.7 to -15.9
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -23.5 · 95% CI -31.9 to -15.1
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -31.2 · 95% CI -39.5 to -22.9
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -18.6 · 95% CI -27.6 to -9.7
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0006 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.8 · 95% CI -24.7 to -6.8
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -22.6 · 95% CI -31.4 to -13.8
SecondaryPercent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 242.27 ± 2.807-16.40 ± 2.835-12.91 ± 2.805-19.64 ± 2.788
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -18.66 · 95% CI -26.53 to -10.80
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repeated Measures · p = 0.0002 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -15.18 · 95% CI -23.00 to -7.36
  • Placebo vs ARO-ANG3 200 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -21.90 · 95% CI -29.69 to -14.12
SecondaryPercent Change From Baseline in Fasting Total ApoB Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Total ApoB Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 42.57 ± 2.074-14.00 ± 2.116-11.71 ± 2.093-18.47 ± 2.105
Week 81.51 ± 2.518-15.85 ± 2.553-10.66 ± 2.525-15.05 ± 2.556
Week 122.26 ± 2.656-14.96 ± 2.653-7.69 ± 2.617-15.10 ± 2.606
Week 16-1.36 ± 2.524-15.72 ± 2.543-14.33 ± 2.513-21.66 ± 2.509
Week 20-0.28 ± 2.350-17.99 ± 2.370-14.52 ± 2.329-18.58 ± 2.326
Week 242.27 ± 2.807-16.40 ± 2.835-12.91 ± 2.805-19.64 ± 2.788
Week 280.51 ± 2.688-15.39 ± 2.725-12.47 ± 2.703-17.03 ± 2.680
Week 36-2.30 ± 2.777-12.85 ± 2.801-9.07 ± 2.791-13.21 ± 2.756
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -16.57 · 95% CI -22.41 to -10.74
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.28 · 95% CI -20.08 to -8.48
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -21.04 · 95% CI -26.85 to -15.23
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.35 · 95% CI -24.42 to -10.29
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0008 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -12.16 · 95% CI -19.19 to -5.13
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -16.56 · 95% CI -23.62 to -9.50
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.21 · 95% CI -24.61 to -9.81
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0082 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -9.95 · 95% CI -17.30 to -2.60
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.35 · 95% CI -24.68 to -10.03
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.36 · 95% CI -21.42 to -7.30
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0003 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -12.97 · 95% CI -19.98 to -5.95
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -20.30 · 95% CI -27.30 to -13.29
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.71 · 95% CI -24.29 to -11.13
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.23 · 95% CI -20.75 to -7.72
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -18.30 · 95% CI -24.80 to -11.79
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -18.66 · 95% CI -26.53 to -10.80
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0002 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.18 · 95% CI -23.00 to -7.36
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -21.90 · 95% CI -29.69 to -14.12
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.90 · 95% CI -23.44 to -8.35
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0008 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -12.98 · 95% CI -20.49 to -5.46
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.54 · 95% CI -25.01 to -10.07
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0081 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -10.55 · 95% CI -18.32 to -2.77
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0871 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -6.76 · 95% CI -14.52 to 0.99
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0058 (MMRM model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms, and treatment by visit and treatment by baseline as interaction terms.) · Difference: -10.91 · 95% CI -18.61 to -3.20
SecondaryPercent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 245.0 ± 4.53-11.0 ± 4.58-4.3 ± 4.56-15.1 ± 4.51
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Models Repeated Measures · p = 0.0138 (Model includes treatment arm, study visit, and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs. placebo at week 24: -16.0 · 95% CI -28.7 to -3.3
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repated Measures · p = 0.1480 (Model includes treatment arm, study visit, and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -9.3 · 95% CI -22.0 to 3.3
  • Placebo vs ARO-ANG3 200 mg · Mxed Models Repeated Measures · p = 0.0019 (Model includes treatment arm, study visit, and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -20.2 · 95% CI -32.8 to -7.5
SecondaryPercent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 45.1 ± 3.95-8.3 ± 4.03-3.4 ± 4.02-13.7 ± 3.98
Week 83.7 ± 4.78-10.1 ± 4.85-0.7 ± 4.83-10.8 ± 4.81
Week 127.7 ± 7.31-7.6 ± 7.367.9 ± 7.34-12.1 ± 7.23
Week 163.6 ± 4.51-9.5 ± 4.56-7.4 ± 4.52-19.5 ± 4.48
Week 201.8 ± 4.26-12.2 ± 4.31-6.9 ± 4.28-15.3 ± 4.22
Week 245.0 ± 4.53-11.0 ± 4.58-4.3 ± 4.56-15.1 ± 4.51
Week 280.2 ± 4.67-9.1 ± 4.75-2.4 ± 4.74-11.3 ± 4.66
Week 363.1 ± 5.75-8.9 ± 5.813.7 ± 5.82-4.4 ± 5.71
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0192 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -13.3 · 95% CI -24.5 to -2.2
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1362 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -8.4 · 95% CI -19.6 to 2.7
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0010 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -18.7 · 95% CI -29.8 to -7.7
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0428 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -13.9 · 95% CI -27.3 to -0.5
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.5122 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -4.5 · 95% CI -17.9 to 8.9
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0331 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.6 · 95% CI -27.9 to -1.2
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1400 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.4 · 95% CI -35.8 to 5.1
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.9854 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: 0.2 · 95% CI -20.2 to 20.6
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0552 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -19.8 · 95% CI -40.1 to 0.4
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0430 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -13.1 · 95% CI -25.7 to -0.4
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0871 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -11.0 · 95% CI -23.6 to 1.6
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0004 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -23.1 · 95% CI -35.7 to -10.6
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0219 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.0 · 95% CI -25.9 to -2.0
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1526 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -8.7 · 95% CI -20.6 to 3.2
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0049 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.0 · 95% CI -28.9 to -5.2
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0138 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -16.0 · 95% CI -28.7 to -3.3
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1480 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -9.3 · 95% CI -22.0 to 3.3
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0019 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -20.2 · 95% CI -32.8 to -7.5
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1660 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -9.3 · 95% CI -22.4 to 3.9
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.6964 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -2.6 · 95% CI -15.7 to 10.5
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0831 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -11.5 · 95% CI -24.5 to 1.5
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.1425 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -12.0 · 95% CI -28.2 to 4.1
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = 0.9494 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: 0.5 · 95% CI -15.6 to 16.6
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = 0.3535 (MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -7.5 · 95% CI -23.5 to 8.4
SecondaryPercent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 241.24 ± 2.801-53.02 ± 2.829-68.52 ± 2.807-72.45 ± 2.761
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo: -54.26 · 95% CI -62.11 to -46.40
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -69.76 · 95% CI -77.58 to -61.95
  • Placebo vs ARO-ANG3 200 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -73.69 · 95% CI -81.44 to -65.93
SecondaryPercent Change From Baseline in ANGPTL3 Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in ANGPTL3 Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 45.54 ± 2.353-62.11 ± 2.388-75.25 ± 2.401-79.15 ± 2.365
Week 82.97 ± 3.023-56.09 ± 3.074-69.01 ± 3.066-73.47 ± 3.045
Week 127.38 ± 3.599-47.72 ± 3.635-63.17 ± 3.608-66.62 ± 3.542
Week 168.48 ± 2.379-63.73 ± 2.400-75.61 ± 2.379-80.52 ± 2.345
Week 204.35 ± 2.338-60.50 ± 2.360-73.10 ± 2.347-76.25 ± 2.299
Week 241.24 ± 2.801-53.02 ± 2.829-68.52 ± 2.807-72.45 ± 2.761
Week 285.18 ± 2.879-49.57 ± 2.920-61.43 ± 2.921-68.19 ± 2.852
Week 363.73 ± 3.110-41.70 ± 3.158-53.41 ± 3.155-59.85 ± 3.066
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -67.65 · 95% CI -74.26 to -61.04
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -80.80 · 95% CI -87.42 to -74.17
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -84.69 · 95% CI -91.27 to -78.12
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -59.07 · 95% CI -67.57 to -50.57
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -71.98 · 95% CI -80.47 to -63.50
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -76.44 · 95% CI -84.90 to -67.99
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -55.10 · 95% CI -65.18 to -45.01
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -70.55 · 95% CI -80.60 to -60.51
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -74.00 · 95% CI -83.95 to -64.04
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -72.22 · 95% CI -78.88 to -65.56
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -84.09 · 95% CI -90.72 to -77.46
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -89.00 · 95% CI -95.59 to -82.42
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -64.86 · 95% CI -71.40 to -58.31
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -77.45 · 95% CI -83.98 to -70.93
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -80.60 · 95% CI -87.06 to -74.14
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -54.26 · 95% CI -62.11 to -46.40
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -69.76 · 95% CI -77.58 to -61.95
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -73.69 · 95% CI -81.44 to -65.93
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -54.75 · 95% CI -62.84 to -46.67
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -66.60 · 95% CI -74.69 to -58.52
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -73.37 · 95% CI -81.36 to -65.38
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -45.43 · 95% CI -54.17 to -36.69
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -57.15 · 95% CI -65.88 to -48.41
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -63.58 · 95% CI -72.19 to -54.97
SecondaryPercent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
Time frame:
Baseline, Week 24
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 243.1 ± 2.91-9.0 ± 2.94-18.5 ± 2.96-21.5 ± 2.89
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Models Repeated Measures · p = 0.0039 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -12.0 · 95% CI -20.2 to -3.9
  • Placebo vs ARO-ANG3 100 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Difference vs placebo at week 24: -21.6 · 95% CI -29.8 to -13.4
  • Placebo vs ARO-ANG3 200 mg · Mixed Models Repeated Measures · p = <.0001 (Model includes treatment arm, study visit, randomization stratification factor (LDL-C at Screening \[≥100 mg/dL vs \<100 mg/dL\]),and baseline value as model terms. Model also includes treatment by visit and treatment by baseline as interaction terms.) · Differeence vs placebo at week 24: -24.5 · 95% CI -32.6 to -16.5
SecondaryPercent Change From Baseline in Fasting HDL-C Over Time
Time frame:
Baseline, up to Week 36 (double-blind treatment period)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting HDL-C Over Time
percentage changePlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Week 4-0.3 ± 2.59-13.9 ± 2.63-25.5 ± 2.68-24.8 ± 2.61
Week 80.4 ± 2.67-14.5 ± 2.71-25.0 ± 2.74-25.8 ± 2.69
Week 122.0 ± 3.10-7.0 ± 3.11-18.7 ± 3.14-18.2 ± 3.05
Week 162.1 ± 2.99-15.8 ± 3.02-28.5 ± 3.04-30.2 ± 2.96
Week 203.4 ± 2.89-11.3 ± 2.92-25.1 ± 2.94-27.1 ± 2.86
Week 243.1 ± 2.91-9.0 ± 2.94-18.5 ± 2.96-21.5 ± 2.89
Week 283.0 ± 2.78-5.5 ± 2.82-14.7 ± 2.87-18.6 ± 2.77
Week 366.4 ± 2.78-1.4 ± 2.82-13.7 ± 2.86-9.4 ± 2.75
Statistical analysis
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0003 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -13.7 · 95% CI -20.9 to -6.4
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -25.3 · 95% CI -32.6 to -17.9
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -24.5 · 95% CI -31.8 to -17.3
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.0 · 95% CI -22.4 to -7.5
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -25.4 · 95% CI -33.0 to -17.9
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -26.2 · 95% CI -33.7 to -18.7
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0429 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -8.9 · 95% CI -17.6 to -0.3
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -20.7 · 95% CI -29.4 to -12.0
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -20.1 · 95% CI -28.7 to -11.6
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.9 · 95% CI -26.2 to -9.5
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -30.6 · 95% CI -39.0 to -22.2
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -32.3 · 95% CI -40.5 to -24.0
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0005 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -14.6 · 95% CI -22.7 to -6.5
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -28.4 · 95% CI -36.6 to -20.3
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -30.4 · 95% CI -38.4 to -22.4
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0039 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -12.0 · 95% CI -20.2 to -3.9
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -21.6 · 95% CI -29.8 to -13.4
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -24.5 · 95% CI -32.6 to -16.5
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0343 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -8.4 · 95% CI -16.2 to -0.6
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -17.7 · 95% CI -25.6 to -9.8
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -21.5 · 95% CI -29.3 to -13.8
  • Placebo vs ARO-ANG3 50 mg · Mixed Model Repeated Measures (MMRM) · p = 0.0501 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -7.8 · 95% CI -15.6 to 0.0
  • Placebo vs ARO-ANG3 100 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -20.1 · 95% CI -27.9 to -12.2
  • Placebo vs ARO-ANG3 200 mg · Mixed Model Repeated Measures (MMRM) · p = <.0001 (Includes treatment arm, study visit, randomization stratification factor (level of LDL-C at Screening \[≥100 mg/dL versus \<100 mg/dL\]),and baseline value as model terms. Also includes treatment by visit and treatment by baseline as interaction terms.) · Difference: -15.8 · 95% CI -23.5 to -8.1
SecondaryPlasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period
Time frame:
Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period)
Reported as:
Mean · ng/mL
Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period
ng/mLARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
Day 1, Pre-Dose0.0000 ± 0.000002.6685 ± 12.228710.0000 ± 0.00000
Day 1, 15 Minutes Post-Dose57.6941 ± 28.0577863.5267 ± 55.85108154.7823 ± 129.43190
Day 1, 1 Hour Post-Dose75.3752 ± 31.39048130.3387 ± 81.73501221.5979 ± 105.15447
Day 1, 3 Hours Post-Dose77.9834 ± 34.90982143.7746 ± 79.62215259.2799 ± 144.46149
Day 1, 6 Hours Post-Dose83.9751 ± 53.53021152.0097 ± 91.30854280.0843 ± 153.62465
Day 2, 24 Hours Post-Dose13.3369 ± 8.8589333.3047 ± 16.3104977.9982 ± 31.94202
Week 12, Pre-Dose0.0000 ± 0.000000.0653 ± 0.276951.9366 ± 7.74650
Week 12, 15 Minutes Post-Dose54.2741 ± 43.9583568.3054 ± 52.28977134.0610 ± 138.22698
Week 12, 1 Hour Post-Dose76.2131 ± 34.49650130.2505 ± 52.66507247.9728 ± 112.83368
Week 12, 3 Hours Post-Dose78.2496 ± 36.47898152.0302 ± 78.31595304.2006 ± 178.69258
Week 12, 6 Hours Post-Dose87.6919 ± 37.30155154.3280 ± 71.93043312.6397 ± 174.86753
Week 12, 24 Hours Post-Dose15.3604 ± 13.0380736.2506 ± 18.33432103.1401 ± 60.85616
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24

TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction.

Time frame:
From first dose of IP up to Week 24
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24
ParticipantsPlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
All TEAEs (Including Serious)30372939
Serious TEAEs3301
SecondaryNumber of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period

Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

Time frame:
up to Week 36 (double-blind treatment period)
Reported as:
Count of participants · Participants
Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period
ParticipantsPlacebo (Pooled)ARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mg
All Treatment-Emergent Adverse Events (TEAEs)35403442
Treatment-related TEAEs812812
Serious TEAEs4501
TEAEs leading to study drug discontinuation2010
Deaths1000
Local Injection Site Reactions (LISR)1032
SecondaryNumber of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period

Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= an AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.

Time frame:
From first dose of study drug in the OLE up to Month 24 (open-label extension)
Reported as:
Count of participants · Participants
Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period
ParticipantsPlacebo/ARO-ANG3 50mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200 mg/ARO-ANG3 200 mg
All Treatment-Emergent Adverse Events (TEAEs)102713301031
Treatment-related TEAEs284606
Serious TEAEs342525
TEAEs leading to study drug discontinuation001211
Deaths000100
SecondaryPercent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period
percentage changeARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 1-10.02 ± 8.711-34.78 ± 3.941-2.09 ± 13.925-39.64 ± 3.3577.87 ± 12.061-51.88 ± 2.612
Percent Change from Baseline to OLE Month 1-43.74 ± 5.555-45.32 ± 3.994-50.45 ± 7.323-52.86 ± 3.051-49.57 ± 5.990-62.76 ± 2.262
Percent Change from Baseline to OLE Month 2-47.14 ± 4.687-45.78 ± 4.449-48.96 ± 7.586-51.51 ± 2.712-48.98 ± 6.568-58.66 ± 2.135
Percent Change from Baseline to OLE Month 3-40.67 ± 5.792-42.51 ± 3.294-42.05 ± 8.623-48.07 ± 3.255-40.73 ± 8.993-56.59 ± 2.225
Percent Change from Baseline to OLE Month 6-45.81 ± 7.065-48.67 ± 4.081-48.62 ± 7.597-46.81 ± 3.828-46.34 ± 8.818-57.14 ± 2.697
Percent Change from Baseline to OLE Month 12-40.57 ± 9.384-47.10 ± 3.546-52.40 ± 6.578-50.56 ± 4.288-49.06 ± 3.275-58.36 ± 2.110
Percent Change from Baseline to OLE Month 15-47.40 ± 6.442-47.33 ± 3.969-58.81 ± 4.310-56.23 ± 2.968-44.56 ± 4.440-53.57 ± 4.055
Percent Change from Baseline to OLE Month 18-48.07 ± 6.892-48.48 ± 3.041-55.29 ± 5.170-55.11 ± 3.039-49.25 ± 4.860-51.71 ± 4.761
Percent Change from Baseline to OLE Month 21-41.86 ± 9.334-45.95 ± 3.609-58.42 ± 3.043-55.23 ± 3.101-49.30 ± 4.388-47.42 ± 6.810
Percent Change from Baseline to OLE Month 24-48.23 ± 11.315-53.83 ± 3.490-61.61 ± 8.343-56.65 ± 3.545-51.88 ± 3.705-58.96 ± 3.563
SecondaryPercent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period
percentage changePlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 16.70 ± 13.049-19.95 ± 3.532-5.02 ± 5.171-16.02 ± 3.824-2.53 ± 3.750-23.12 ± 3.116
Percent Change from Baseline to OLE Month 1-14.79 ± 6.493-22.99 ± 3.544-25.80 ± 4.039-25.23 ± 3.912-28.13 ± 3.930-33.41 ± 3.158
Percent Change from Baseline to OLE Month 2-14.70 ± 5.087-25.54 ± 3.730-22.32 ± 5.340-22.98 ± 3.151-28.43 ± 4.168-30.35 ± 3.013
Percent Change from Baseline to OLE Month 3-14.32 ± 6.774-20.71 ± 3.770-19.61 ± 4.659-22.97 ± 3.462-25.19 ± 4.215-26.68 ± 3.107
Percent Change from Baseline to OLE Month 6-10.42 ± 7.330-22.11 ± 4.372-26.53 ± 4.347-24.38 ± 3.392-30.83 ± 4.832-27.84 ± 3.414
Percent Change from Baseline to OLE Month 12-13.72 ± 9.131-22.82 ± 4.267-24.42 ± 7.159-30.48 ± 3.626-28.60 ± 3.545-30.08 ± 2.731
Percent Change from Baseline to OLE Month 15-13.02 ± 13.661-24.01 ± 4.257-25.66 ± 3.442-31.53 ± 3.040-25.86 ± 4.405-27.73 ± 3.387
Percent Change from Baseline to OLE Month 18-23.39 ± 6.010-23.26 ± 3.579-25.34 ± 4.315-33.90 ± 3.422-29.09 ± 4.005-27.88 ± 3.495
Percent Change from Baseline to OLE Month 21-13.13 ± 14.219-25.07 ± 3.492-34.23 ± 3.783-30.46 ± 2.642-28.66 ± 4.590-25.75 ± 3.735
Percent Change from Baseline to OLE Month 24-32.24 ± 14.568-27.52 ± 5.126-37.23 ± 3.633-31.95 ± 4.492-24.24 ± 9.558-30.82 ± 4.407
SecondaryPercent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period
percentage changePlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 16.57 ± 8.959-13.49 ± 3.086-10.22 ± 4.678-7.48 ± 2.924-3.88 ± 3.080-11.77 ± 3.309
Percent Change from Baseline to OLE Month 16.82 ± NA—-1.65 ± NA-4.45 ± NA—-21.63 ± NA
Percent Change from Baseline to OLE Month 20.31 ± 8.213-21.00 ± 6.460-3.56 ± 6.243-7.93 ± 5.968-11.37 ± 16.839-7.58 ± 6.338
Percent Change from Baseline to OLE Month 3-5.48 ± 13.745-13.01 ± 7.131-0.30 ± 3.518-7.09 ± 5.090-13.13 ± 4.275-8.34 ± 3.722
Percent Change from Baseline to OLE Month 6-1.23 ± 7.644-13.89 ± 3.645-13.84 ± 3.803-11.91 ± 3.517-18.14 ± 2.810-14.04 ± 3.504
Percent Change from Baseline to OLE Month 12-3.46 ± 9.733-12.63 ± 3.662-13.78 ± 6.382-15.14 ± 3.520-13.87 ± 2.996-15.90 ± 2.835
Percent Change from Baseline to OLE Month 15-8.08 ± 9.722-12.73 ± 3.587-13.40 ± 3.056-16.23 ± 2.661-11.27 ± 4.524-13.05 ± 3.530
Percent Change from Baseline to OLE Month 18-14.34 ± 5.296-13.83 ± 3.624-14.12 ± 3.655-19.88 ± 2.991-13.63 ± 3.819-13.92 ± 3.741
Percent Change from Baseline to OLE Month 210.08 ± 10.835-13.42 ± 3.462-21.03 ± 3.791-15.03 ± 2.910-15.70 ± 4.187-11.85 ± 3.789
Percent Change from Baseline to OLE Month 24-6.57 ± 11.292-14.39 ± 5.371-24.76 ± 4.680-16.73 ± 4.236-10.27 ± 8.790-18.04 ± 4.441
SecondaryPercent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period
percentage changePlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 116.61 ± 13.866-7.68 ± 4.934-1.59 ± 8.0794.59 ± 7.0534.13 ± 5.905-2.82 ± 5.633
Percent Change from Baseline to OLE Month 16.61 ± 8.960-4.90 ± 5.203-7.43 ± 5.762-0.07 ± 7.6543.74 ± 16.591-10.01 ± 4.929
Percent Change from Baseline to OLE Month 25.75 ± 6.546-10.81 ± 5.105-3.40 ± 7.1197.38 ± 12.4733.50 ± 20.049-10.08 ± 4.989
Percent Change from Baseline to OLE Month 33.79 ± 8.934-2.69 ± 5.570-2.47 ± 7.8391.94 ± 7.6285.74 ± 20.327-1.59 ± 6.358
Percent Change from Baseline to OLE Month 616.09 ± 11.331-2.03 ± 6.503-10.68 ± 5.700-9.92 ± 4.1373.32 ± 20.431-2.80 ± 6.230
Percent Change from Baseline to OLE Month 126.95 ± 14.056-2.77 ± 6.090-4.64 ± 9.376-8.25 ± 7.5734.05 ± 18.896-6.97 ± 4.466
Percent Change from Baseline to OLE Month 158.54 ± 17.305-7.84 ± 6.363-6.14 ± 6.380-5.41 ± 11.6385.82 ± 18.362-7.85 ± 5.264
Percent Change from Baseline to OLE Month 18-9.73 ± 8.195-5.88 ± 5.801-4.52 ± 7.677-13.20 ± 7.8826.86 ± 21.962-8.43 ± 5.346
Percent Change from Baseline to OLE Month 219.29 ± 18.925-6.14 ± 5.553-12.81 ± 7.465-4.47 ± 8.744-15.64 ± 7.008-2.16 ± 5.032
Percent Change from Baseline to OLE Month 24-7.17 ± 22.117-10.57 ± 6.996-12.81 ± 9.496-13.83 ± 5.902-9.58 ± 14.506-6.18 ± 6.423
SecondaryPercent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period
percentage changePlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 13.41 ± 5.372-41.57 ± 4.4174.47 ± 7.595-56.81 ± 3.1660.79 ± 4.664-59.24 ± 3.551
Percent Change from Baseline to OLE Month 1-59.55 ± 3.490-65.83 ± 2.836-77.02 ± 2.699-76.03 ± 1.982-74.62 ± 3.753-77.96 ± 2.273
Percent Change from Baseline to OLE Month 2-53.85 ± 3.393-60.01 ± 3.812-67.75 ± 4.771-71.21 ± 2.367-70.19 ± 3.928-74.59 ± 2.775
Percent Change from Baseline to OLE Month 3-43.36 ± 5.072-48.56 ± 6.842-61.65 ± 4.510-65.54 ± 3.020-64.79 ± 5.478-68.91 ± 3.310
Percent Change from Baseline to OLE Month 6-49.22 ± 5.280-54.18 ± 4.076-67.23 ± 4.070-68.85 ± 2.867-69.38 ± 3.736-67.04 ± 3.743
Percent Change from Baseline to OLE Month 12-55.48 ± 5.056-55.20 ± 4.666-71.03 ± 4.370-69.32 ± 3.691-63.23 ± 5.801-62.00 ± 4.122
Percent Change from Baseline to OLE Month 15-53.01 ± 3.998-52.97 ± 4.560-65.80 ± 4.669-65.28 ± 6.196-64.57 ± 3.909-55.73 ± 5.734
Percent Change from Baseline to OLE Month 18-36.82 ± 9.076-39.57 ± 5.638-65.71 ± 4.877-65.97 ± 3.280-61.38 ± 4.943-55.31 ± 4.725
Percent Change from Baseline to OLE Month 21-40.12 ± 5.814-43.45 ± 5.176-63.26 ± 4.176-64.68 ± 3.414-58.10 ± 4.837-55.43 ± 4.784
Percent Change from Baseline to OLE Month 24-44.08 ± 10.028-50.18 ± 6.570-48.46 ± 14.321-62.95 ± 4.439-61.52 ± 3.012-63.89 ± 4.009
SecondaryPercent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period
Time frame:
Baseline, OLE Baseline, Months 1-24 (open-label extension)
Reported as:
Least squares mean · percentage change
Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period
percentage changePlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200mg
Percent Change from Baseline to OLE Baseline/OLE Day 113.70 ± 6.0361.67 ± 3.3607.70 ± 5.318-12.88 ± 3.1474.80 ± 4.562-11.26 ± 3.771
Percent Change from Baseline to OLE Month 1-10.68 ± 8.416-12.31 ± 3.791-26.62 ± 4.804-28.81 ± 3.214-14.33 ± 8.371-28.27 ± 3.705
Percent Change from Baseline to OLE Month 2-9.46 ± 6.308-10.98 ± 3.588-19.64 ± 4.846-24.78 ± 3.397-13.48 ± 7.252-28.24 ± 3.362
Percent Change from Baseline to OLE Month 3-8.80 ± 5.376-9.96 ± 3.318-15.50 ± 4.847-22.29 ± 3.771-12.81 ± 5.209-19.78 ± 3.504
Percent Change from Baseline to OLE Month 6-8.26 ± 6.279-3.95 ± 4.247-21.38 ± 6.028-26.54 ± 3.486-13.75 ± 6.207-20.43 ± 4.082
Percent Change from Baseline to OLE Month 12-13.83 ± 7.363-16.58 ± 3.672-22.23 ± 5.893-26.51 ± 3.816-5.47 ± 5.504-18.32 ± 4.314
Percent Change from Baseline to OLE Month 15-9.01 ± 6.448-12.02 ± 5.116-19.76 ± 5.356-29.44 ± 3.110-14.07 ± 5.004-15.04 ± 4.116
Percent Change from Baseline to OLE Month 18-10.53 ± 6.499-4.80 ± 5.980-21.60 ± 5.268-28.55 ± 3.462-11.86 ± 4.787-16.39 ± 4.648
Percent Change from Baseline to OLE Month 21-3.87 ± 6.823-12.48 ± 3.816-22.77 ± 4.713-26.12 ± 3.535-16.68 ± 2.024-17.82 ± 3.788
Percent Change from Baseline to OLE Month 24-8.97 ± 10.168-11.66 ± 5.293-20.28 ± 15.397-27.31 ± 4.225-16.01 ± 3.759-24.10 ± 5.009

Adverse events

Collected over All-cause mortality: From randomization through Month 24. Adverse events: From first dose of study drug through Week 36 (double-blind period); from first dose of open-label study drug up to Month 24 (open-label extension).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo1/51 (2%)4/51 (7.8%)41/51 (80.4%)
ARO-ANG3 50 mg0/50 (0%)5/50 (10%)38/50 (76%)
ARO-ANG3 100 mg0/51 (0%)0/51 (0%)41/51 (80.4%)
ARO-ANG3 200 mg0/52 (0%)1/52 (1.9%)42/52 (80.8%)
Placebo/ARO-ANG3 50 mg0/13 (0%)3/13 (23.1%)10/13 (76.9%)
ARO-ANG3 50 mg/ARO-ANG3 50 mg0/36 (0%)4/36 (11.1%)31/36 (86.1%)
Placebo/ARO-ANG3 100 mg0/14 (0%)2/14 (14.3%)14/14 (100%)
ARO-ANG3 100 mg/ARO-ANG3 100 mg1/39 (2.6%)5/39 (12.8%)34/39 (87.2%)
Placebo/ARO-ANG3 200 mg0/13 (0%)2/13 (15.4%)11/13 (84.6%)
ARO-ANG3 200mg/ARO-ANG3 200 mg0/41 (0%)5/41 (12.2%)34/41 (82.9%)
Most frequent serious events
Showing 10 of 40
Most frequent serious events
EventPlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgPlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200 mg
Atrial fibrillationCardiac disorders0/510/500/510/521/130/360/140/390/130/41
Supraventricular tachycardiaCardiac disorders0/510/500/510/521/130/360/140/390/130/41
Incarcerated umbilical herniaGastrointestinal disorders0/510/500/510/521/130/360/140/390/130/41
Pancreatitis acuteGastrointestinal disorders0/510/500/510/520/130/360/140/391/130/41
InfluenzaInfections and infestations0/510/500/510/521/130/360/140/390/130/41
PneumoniaInfections and infestations0/510/500/510/520/130/361/140/391/130/41
Acute respiratory failureRespiratory, thoracic and mediastinal disorders0/510/500/510/521/130/360/140/390/130/41
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders0/510/500/510/520/130/361/140/391/130/41
Non-cardiac chest painGeneral disorders0/511/500/510/520/131/361/140/390/130/41
Acute kidney injuryRenal and urinary disorders0/510/500/510/520/130/360/140/390/132/41
Most frequent other events
Showing 10 of 189
Most frequent other events
EventPlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgPlacebo/ARO-ANG3 50 mgARO-ANG3 50 mg/ARO-ANG3 50 mgPlacebo/ARO-ANG3 100 mgARO-ANG3 100 mg/ARO-ANG3 100 mgPlacebo/ARO-ANG3 200 mgARO-ANG3 200mg/ARO-ANG3 200 mg
COVID-19Infections and infestations14/5116/5016/5118/523/1314/365/1413/394/1315/41
Upper respiratory tract infectionInfections and infestations7/518/509/5111/521/136/363/149/392/139/41
Urinary tract infectionInfections and infestations5/516/506/5112/522/134/362/144/391/138/41
GastroenteritisInfections and infestations4/510/501/512/520/130/363/141/390/132/41
Type 2 diabetes mellitusMetabolism and nutrition disorders5/514/502/517/520/133/363/142/391/137/41
ArthralgiaMusculoskeletal and connective tissue disorders4/513/504/514/520/133/363/144/391/134/41
HeadacheNervous system disorders6/516/503/519/521/134/363/143/391/136/41
Back painMusculoskeletal and connective tissue disorders1/515/502/518/520/135/360/142/391/138/41
DiarrhoeaGastrointestinal disorders3/512/504/514/520/131/361/144/392/134/41
Gastrooesophageal reflux diseaseGastrointestinal disorders3/512/501/512/522/132/361/141/390/132/41

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgTotal
Mean60.2 ± 11.3060.4 ± 12.6860.0 ± 9.8961.5 ± 12.5360.5 ± 11.58
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgTotal
Female2425222495
Male27262927109
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgTotal
Hispanic or Latino1212181355
Not Hispanic or Latino39393338149
Unknown or Not Reported00000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgTotal
White48494949195
Black or African American11103
Asian10113
Native Hawaiian or Other Pacific Islander01001
Other10012
Mean Triglycerides (TG) at Baseline
Mean Triglycerides (TG) at Baseline(mg/dL)PlaceboARO-ANG3 50 mgARO-ANG3 100 mgARO-ANG3 200 mgTotal
Mean235.15 ± 86.117242.47 ± 79.864246.71 ± 97.996259.97 ± 93.320246.08 ± 89.386
08

Study locations

24 sites
  • Research Site 5
    Huntington Park, California 90255, United States
  • Research Site 7
    Hialeah, Florida 33012, United States
  • Research Site 17
    Miami, Florida 33144, United States
  • Research Site 8
    Port Orange, Florida 32127, United States
  • Research Site 24
    Minneapolis, Minnesota 55455, United States
  • Research Site 10
    Omaha, Nebraska 68114, United States
  • Research Site 23
    Las Vegas, Nevada 89121, United States
  • Research Site 22
    New York, New York 10029, United States
  • Research Site 15
    Greensboro, North Carolina 27408, United States
  • Research Site 2
    Morehead City, North Carolina 28557, United States
  • Research Site 1
    Marion, Ohio 43302, United States
  • Research Site 4
    Camp Hill, Pennsylvania 17011, United States
  • Research Site 11
    Houston, Texas 77030, United States
  • Research Site 6
    Blacktown, New South Wales 2148, Australia
  • Research Site 21
    Sippy Downs, Queensland 4556, Australia
  • Research Site 18
    Nedlands, 6009, Australia
  • Research Site 25
    London, Ontario N6A 5A5, Canada
  • Research Site 16
    Chicoutimi, Quebec G7H 7K9, Canada
  • Research Site 12
    Québec, G1G 3Z4, Canada
  • Research Site 9
    Québec, H7T2P5, Canada
  • Research Site 19
    Birkenhead, 0626, New Zealand
  • Research Site 13
    Christchurch, 8011, New Zealand
  • Research Site 20
    Hamilton, 3200, New Zealand
  • Research Site 14
    Rotorua, 3010, New Zealand
09

References and documents

Publications

  • Rosenson RS, Gaudet D, Ballantyne CM, Nicholls SJ, Lucas KJ, Leeper NJ, Zhou R, Aiyer L, Hellawell J, Watts GF. Longer-Term Efficacy and Safety of Zodasiran in Patients with Mixed Hyperlipidaemia. Eur J Prev Cardiol. 2026 Jul 24:zwag376. doi: 10.1093/eurjpc/zwag376. Online ahead of print. PubMed 42496147 ↗
  • Rosenson RS, Gaudet D, Hegele RA, Ballantyne CM, Nicholls SJ, Lucas KJ, San Martin J, Zhou R, Muhsin M, Chang T, Hellawell J, Watts GF; ARCHES-2 Trial Team. Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia. N Engl J Med. 2024 Sep 12;391(10):913-925. doi: 10.1056/NEJMoa2404147. Epub 2024 May 29. PubMed 38809174 ↗
  • Dimitriadis K, Theofilis P, Iliakis P, Pyrpyris N, Dri E, Sakalidis A, Soulaidopoulos S, Tsioufis P, Fragkoulis C, Chrysohoou C, Tsiachris D, Tsioufis K. Management of dyslipidemia in coronary artery disease: the present and the future. Coron Artery Dis. 2024 Sep 1;35(6):516-524. doi: 10.1097/MCA.0000000000001375. Epub 2024 Apr 29. PubMed 38682459 ↗

Study documents

  • Study protocol · Nov 22, 2022
  • Statistical analysis plan · Oct 5, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04832971
Lead sponsor
Arrowhead Pharmaceuticals
Responsible party
Sponsor
First posted
Apr 6, 2021
Start date
Jun 28, 2021
Primary completion
Aug 30, 2022
Completion
Sep 25, 2024
Results posted
Jan 16, 2024
Last update
Dec 3, 2025

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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