CompletedNCT03728634Updated Dec 19, 2022Results posted

Evaluate the Safety and Tolerability, as Well as the Pharmacokinetic and Pharmacodynamic Profiles of Single and Multiple Doses of Eplontersen Administered Subcutaneously to Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis (hATTR ).

A Phase 1/2 interventional study of ION-682884 and Placebo in Healthy Volunteers and hATTR Amyloidosis, sponsored by Ionis Pharmaceuticals, Inc.. Completed at 1 site in Canada. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-12-19.

Sponsored by Ionis Pharmaceuticals, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 47
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study summary

To evaluate the safety and tolerability, as well as the pharmacokinetic and pharmacodynamic profiles of single and multiple doses of Eplontersen administered subcutaneously to healthy volunteers and patients with Hereditary Transthyretin-Mediated Amyloidosis (hATTR ).

Read the detailed description

This will be a Phase 1/2, double-blind, randomized, placebo-controlled, dose-escalation study conducted at a single center for the healthy volunteer cohorts in up to 56 participants. It will consist of 1 single-dose cohort and 3 multiple-dose cohorts (n = 12 per cohort, 10 active:2 placebo). The open-label, hATTR patient cohort portion of the study will be conducted at multiple centers.

Conditions studied

Healthy Volunteers
hATTR Amyloidosis

Browse trials for

Amyloidosis 491

In context

Amyloidosis

491 studies on the registry are indexed under Amyloidosis; 135 are open to participants now.

This study's enrollment of 47 is above the median of 40 across 304 interventional studies indexed under Amyloidosis.

Browse Amyloidosis studies →

Lead sponsor

Ionis Pharmaceuticals, Inc. is the lead sponsor of 116 studies on the registry; 10 are open to participants now.

Of its 48 completed or terminated interventional studies of FDA-regulated products, 21 (44%) have results posted.

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

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion Criteria for Healthy Volunteers (Cohorts A, B, C, and E)

Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
Weight ≥ 50 kg and BMI \< 32 kg/m\^2

Exclusion Criteria for Healthy Volunteers (Cohorts A, B, C, and E)

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion including abnormal safety labs
Drug or alcohol dependency or abuse
Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
Blood donation within 28 days
Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Inclusion criteria

Inclusion Criteria for hATTR Patients (Cohort D)

Aged 18 to 82 years at the time of informed consent
Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
Diagnosis of hereditary transthyretin-mediated polyneuropathy
BMI > 16 kg/m2

Exclusion criteria

Exclusion Criteria for hATTR Patients (Cohort D)

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs
Karnofsky performance status ≤ 50
Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
Prior liver transplant or anticipated liver transplant within 1-yr of Screening
New York Heart Association (NYHA) functional classification of ≥ 3
Acute coronary syndrome or major surgery within 3 months of Screening
Other types of amyloidosis
Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 47 participants (actual)

Study arms

Placebo comparator
Multiple Dose Cohort: Placebo
Participants received ION-682884 matching placebo, subcutaneously (SC) once every 4 weeks \[Q4W\] (total of 4 doses) along with daily oral supplemental doses of the recommended daily allowance (RDA) of vitamin A during the 13-week Treatment Period.
Drug: Placebo · Dietary Supplement: Vitamin A
Experimental
Multiple Dose Cohort A: ION-682884 45 mg
Participants received ION-682884, 45 milligrams (mg), SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
Drug: ION-682884 · Dietary Supplement: Vitamin A
Experimental
Multiple Dose Cohort E: ION-682884 60 mg
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
Drug: ION-682884 · Dietary Supplement: Vitamin A
Experimental
Multiple Dose Cohort B: ION-682884 90 mg
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
Drug: ION-682884 · Dietary Supplement: Vitamin A
Placebo comparator
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
Drug: Placebo · Dietary Supplement: Vitamin A
Experimental
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
Drug: ION-682884 · Dietary Supplement: Vitamin A

Interventions

DrugION-682884
ION-682884 administered SC
Also known as: Eplontersen, AKCEA-TTR-LRx, IONIS-TTR-LRx
DrugPlacebo
Placebo comparator calculated volume to match ION-682884 administered SC
Dietary supplementVitamin A
Oral supplement

What researchers measure

Primary outcomes

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of study drug and subsequently worsened or was not present prior to receiving the first dose of study drug but subsequently appeared.
Time frame: Up to Day 176
Percentage of Participants Using Concomitant Medications
A concomitant therapy was any non-protocol-specified drug or substance (including over-the-counter \[OTC\] medications, herbal medications, and vitamin supplements) administered between signing of informed consent and the last study visit.
Time frame: Up to Day 176
Number of Participants With Clinically Significant Laboratory Values
Laboratory parameters included measurement of blood chemistry, hematology, coagulation, complement, or urinalysis parameters for the single-dose and multiple-dose cohorts. Number of participants with clinically significant values in laboratory based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Time frame: Up to Day 176
Number of Participants With Clinically Significant Physical Examination Findings
Physical examination included measurement of height and weight for body mass index (BMI) determination. Number of participants with clinically significant findings in physical examination based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Time frame: Up to Day 176
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
ECG measurements included assessment of ventricular rate (VR), PR interval, QR interval, QT interval, QT corrected using Fridericia's formula (QTcF), and QT corrected using Bazett's formula (QTcB). Number of participants with clinically significant values in electrocardiogram based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Time frame: Up to Day 176

Secondary outcomes

Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
Time frame: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C
CL/F: Apparent Total Clearance of ION-TTR-LRx
Time frame: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C
t1/2λz: Termination Half-Life of ION-TTR-LRx
Time frame: Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C
Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
Time frame: From 0 to 24 hours post-dose on Days 1 and 85
Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
Time frame: Baseline, Days 29 and 99
Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
Time frame: Baseline, Days 29 and 99
Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg
As prespecified in the protocol, this outcome measure was planned to be analyzed only in the Multiple Dose Cohort B: 90 mg ION-682884.
Time frame: 2 hours post-dose on Day 85

Results

Posted Dec 19, 2022

Participant flow

Participant flow — Overall Study
Milestone	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Started	6	10	10	10	2	9
Completed	6	10	10	10	2	9
Not completed	0	0	0	0	0	0

Outcome measures

PrimaryNumber of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of study drug and subsequently worsened or was not present prior to receiving the first dose of study drug but subsequently appeared.

Time frame:: Up to Day 176
Reported as:: Count of participants · Participants

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Participants	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	3	1	3	7	1	4

PrimaryPercentage of Participants Using Concomitant Medications

A concomitant therapy was any non-protocol-specified drug or substance (including over-the-counter \[OTC\] medications, herbal medications, and vitamin supplements) administered between signing of informed consent and the last study visit.

Time frame:: Up to Day 176
Reported as:: Number · percentage of participants

Percentage of Participants Using Concomitant Medications
percentage of participants	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Percentage of Participants Using Concomitant Medications	0.0	0.0	30.0	0.0	0.0	22.2

PrimaryNumber of Participants With Clinically Significant Laboratory Values

Laboratory parameters included measurement of blood chemistry, hematology, coagulation, complement, or urinalysis parameters for the single-dose and multiple-dose cohorts. Number of participants with clinically significant values in laboratory based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.

Time frame:: Up to Day 176
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Laboratory Values
Participants	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Number of Participants With Clinically Significant Laboratory Values	0	0	0	0	0	0

PrimaryNumber of Participants With Clinically Significant Physical Examination Findings

Physical examination included measurement of height and weight for body mass index (BMI) determination. Number of participants with clinically significant findings in physical examination based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.

Time frame:: Up to Day 176
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Physical Examination Findings
Participants	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Number of Participants With Clinically Significant Physical Examination Findings	0	0	0	0	0	0

PrimaryNumber of Participants With Clinically Significant Electrocardiogram (ECG) Values

ECG measurements included assessment of ventricular rate (VR), PR interval, QR interval, QT interval, QT corrected using Fridericia's formula (QTcF), and QT corrected using Bazett's formula (QTcB). Number of participants with clinically significant values in electrocardiogram based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.

Time frame:: Up to Day 176
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
Participants	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values	0	0	0	0	0	0

SecondaryCmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx

Time frame:: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
Reported as:: Geometric mean · micrograms per milliters (µg/mL)

Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
micrograms per milliters (µg/mL)	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	0.143 ± 39.3	0.239 ± 62.6	0.332 ± 43.6	0.542 ± 65.0
Day 85	0.215 ± 66.1	0.282 ± 74.5	0.471 ± 69.5	—

SecondaryTmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx

Time frame:: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
Reported as:: Median · hours

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
hours	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	2.01 (1.00 to 4.00)	6.00 (3.00 to 12.0)	2.25 (1.00 to 6.00)	4.00 (1.00 to 8.00)
Day 85	3.00 (1.00 to 3.00)	1.00 (1.00 to 3.00)	3.00 (1.00 to 8.00)	—

SecondaryAUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx

Time frame:: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C
Reported as:: Geometric mean · micrograms*hour per milliliter (µg*h/mL)

AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
microgramshour per milliliter (µgh/mL)	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	—	—	—	6.78 ± 20.3
Day 85	1.81 ± 36.3	2.73 ± 43.2	4.35 ± 43.2	—

SecondaryCL/F: Apparent Total Clearance of ION-TTR-LRx

Time frame:: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C
Reported as:: Geometric mean · liters per hour (L/h)

CL/F: Apparent Total Clearance of ION-TTR-LRx
liters per hour (L/h)	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	—	—	—	17.7 ± 20.3
Day 85	24.8 ± 36.3	22.0 ± 43.2	20.7 ± 43.2	—

Secondaryt1/2λz: Termination Half-Life of ION-TTR-LRx

Time frame:: Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C
Reported as:: Median · days

t1/2λz: Termination Half-Life of ION-TTR-LRx
days	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	—	—	—	17.9 (12.8 to 40.7)
Day 85	22.3 (10.3 to 52.7)	30.3 (20.1 to 58.9)	24.8 (15.2 to 45.0)	—

SecondaryAe0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period

Time frame:: From 0 to 24 hours post-dose on Days 1 and 85
Reported as:: Geometric mean · micrograms (μg)

Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
micrograms (μg)	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort C: ION-682884 120 mg
Day 1	17.0 ± 54.1	23.5 ± 62.3	29.9 ± 146	87.4 ± 87.9
Day 85	40.6 ± 38.0	68.3 ± 57.2	133 ± 33.8	—

SecondaryChange From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx

Time frame:: Baseline, Days 29 and 99
Reported as:: Mean · milligrams per deciliters (mg/dL)

Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
milligrams per deciliters (mg/dL)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Day 29	-0.225 ± 2.935	-13.40 ± 4.312	-18.63 ± 4.933	-19.42 ± 5.441	0.725 ± 1.732	-20.06 ± 3.615
Day 99	0.908 ± 4.050	-18.60 ± 2.911	-22.02 ± 3.564	-21.91 ± 5.175	—	—

Statistical analysis

Multiple Dose Cohort: Placebo vs Multiple Dose Cohort A: ION-682884 45 mg · Analysis of Variance(ANOVA) · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort E: ION-682884 60 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort B: ION-682884 90 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort A: ION-682884 45 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort E: ION-682884 60 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort B: ION-682884 90 mg · ANOVA · p = <0.001
Single Dose Cohort: Placebo vs Single Dose Cohort C: ION-682884 120 mg · ANOVA · p = 0.036

SecondaryChange From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx

Time frame:: Baseline, Days 29 and 99
Reported as:: Mean · micrograms per milliliters (µg/mL)

Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
micrograms per milliliters (µg/mL)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Day 29	69 ± 5404	-19317 ± 8459	-16383 ± 5191	-21961 ± 8264	1786 ± 623	-24765 ± 7020
Day 99	171 ± 4311	-28693 ± 6132	-20124 ± 3946	-25365 ± 7275	—	—

Statistical analysis

Multiple Dose Cohort: Placebo vs Multiple Dose Cohort A: ION-682884 45 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort E: ION-682884 60 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort B: ION-682884 90 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort A: ION-682884 45 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort E: ION-682884 60 mg · ANOVA · p = <0.001
Multiple Dose Cohort: Placebo vs Multiple Dose Cohort B: ION-682884 90 mg · ANOVA · p = <0.001
Single Dose Cohort: Placebo vs Single Dose Cohort C: ION-682884 120 mg · Wilcoxon Rank Sum Exact Test (2-sided) · p = 0.036

SecondaryPercent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg

As prespecified in the protocol, this outcome measure was planned to be analyzed only in the Multiple Dose Cohort B: 90 mg ION-682884.

Time frame:: 2 hours post-dose on Day 85
Reported as:: Mean · percent abundance of ION-682884 ASO

Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg
percent abundance of ION-682884 ASO	Multiple Dose Cohort B: ION-682884 90 mg
Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg	99.1 ± 1.19

Adverse events

Collected over Up to Day 176. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Multiple Dose Cohort: Placebo	0/6 (0%)	0/6 (0%)	3/6 (50%)
Multiple Dose Cohort A: ION-682884 45 mg	0/10 (0%)	0/10 (0%)	1/10 (10%)
Multiple Dose Cohort E: ION-682884 60 mg	0/10 (0%)	0/10 (0%)	3/10 (30%)
Multiple Dose Cohort B: ION-682884 90 mg	0/10 (0%)	0/10 (0%)	7/10 (70%)
Single Dose Cohort: Placebo	0/2 (0%)	0/2 (0%)	1/2 (50%)
Single Dose Cohort C: ION-682884 120 mg	0/9 (0%)	0/9 (0%)	4/9 (44.4%)

Most frequent other events

Showing 10 of 20

Most frequent other events
Event	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg
Limb discomfortMusculoskeletal and connective tissue disorders	0/6	0/10	0/10	0/10	1/2	0/9
Alanine aminotransferase increasedInvestigations	0/6	0/10	0/10	4/10	0/2	0/9
Blood creatine phosphokinase increasedInvestigations	1/6	0/10	0/10	4/10	0/2	0/9
HeadacheNervous system disorders	1/6	0/10	0/10	0/10	0/2	2/9
Upper respiratory tract infectionInfections and infestations	1/6	0/10	0/10	0/10	0/2	0/9
Nasal congestionRespiratory, thoracic and mediastinal disorders	0/6	0/10	0/10	0/10	0/2	1/9
Rhinitis allergicRespiratory, thoracic and mediastinal disorders	0/6	0/10	0/10	0/10	0/2	1/9
RhinorrhoeaRespiratory, thoracic and mediastinal disorders	0/6	0/10	0/10	0/10	0/2	1/9
NauseaGastrointestinal disorders	0/6	0/10	0/10	0/10	0/2	1/9
Influenza like illnessGeneral disorders	0/6	0/10	0/10	0/10	0/2	1/9

Baseline characteristics

Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).

Age, Continuous
Age, Continuous(years)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg	Total
Mean	49.2 (39.0 to 57.0)	51.6 (28.0 to 61.0)	51.6 (23.0 to 65.0)	51.1 (28.0 to 62.0)	57.0 (53.0 to 61.0)	43.4 (26.0 to 60.0)	49.84 (23.0 to 65.0)

Sex: Female, Male
Sex: Female, Male(Participants)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg	Total
Female	4	3	6	4	2	1	20
Male	2	7	4	6	0	8	27

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg	Total
Hispanic or Latino	0	0	0	0	0	0	0
Not Hispanic or Latino	6	10	10	10	2	9	47
Unknown or Not Reported	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Multiple Dose Cohort: Placebo	Multiple Dose Cohort A: ION-682884 45 mg	Multiple Dose Cohort E: ION-682884 60 mg	Multiple Dose Cohort B: ION-682884 90 mg	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-682884 120 mg	Total
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	1	1	3	3	0	3	11
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	1	3	3	1	0	3	11
White	4	6	4	6	2	3	25
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0

Study locations

1 site

Bio Pharma Services, Inc.
Toronto, Ontario M9L 3A2, Canada

References and documents

Publications

Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7. PubMed 35869634 ↗
Viney NJ, Guo S, Tai LJ, Baker BF, Aghajan M, Jung SW, Yu RZ, Booten S, Murray H, Machemer T, Burel S, Murray S, Buchele G, Tsimikas S, Schneider E, Geary RS, Benson MD, Monia BP. Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data. ESC Heart Fail. 2021 Feb;8(1):652-661. doi: 10.1002/ehf2.13154. Epub 2020 Dec 7. PubMed 33283485 ↗

Study documents

Protocol and statistical analysis plan · Apr 6, 2020

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

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 19, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03728634
Lead sponsor: Ionis Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Nov 2, 2018
Start date: Dec 21, 2018
Primary completion: Feb 20, 2020
Completion: Feb 20, 2020
Results posted: Dec 19, 2022
Last update: Dec 19, 2022

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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