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CompletedNCT01588496TESLAUpdated Nov 29, 2018Results posted

Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities

A Phase 2/3 interventional study of Evolocumab and Placebo in Homozygous Familial Hypercholesterolemia, sponsored by Amgen. Completed at 21 sites in 12 countries. Open to participants aged 12 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-11-29.

Sponsored by Amgen · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
58
Allocation
Randomized
Ages
12 Years to 80 Years
Sex
All
01

Study summary

A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).

Read the detailed description

Study Masking:

Part A: Open Label Part B: Double Blind

02

Conditions studied

  • Homozygous Familial Hypercholesterolemia

Keywords

  • hypercholesterolemia
  • familial hypercholesterolemia
  • homozygous familial hypercholesterolemia
03

In context

Hyperlipoproteinemia Type II

245 studies on the registry are indexed under Hyperlipoproteinemia Type II; 52 are open to participants now.

This study's enrollment of 58 is below the median of 86 across 170 interventional studies indexed under Hyperlipoproteinemia Type II.

Browse Hyperlipoproteinemia Type II studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

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

04

Who can participate

Ages eligible
12 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Males and females ≥ 12 to ≤ 80 years of age
  • Diagnosis of homozygous familial hypercholesterolemia
  • Stable lipid-lowering therapies for at least 4 weeks
  • LDL cholesterol ≥ 130 mg/dl (3.4 mmol/L)
  • Triglyceride ≤ 400 mg/dL (4.5 mmol/L)
  • Bodyweight of ≥ 40 kg at screening.

Exclusion criteria

Exclusion Criteria:

  • LDL or plasma apheresis within 8 weeks prior to randomization
  • New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction \< 30%
  • Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of randomization
  • Planned cardiac surgery or revascularization
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
58 participants (actual)

Study arms

  • Experimental
    Part A: Evolocumab

    Participants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks.

    Biological: Evolocumab

  • Experimental
    Part B: Evolocumab

    Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.

    Biological: Evolocumab

  • Placebo comparator
    Part B: Placebo

    Participants received double-blind placebo subcutaneously once a month for 12 weeks.

    Drug: Placebo

Interventions

  • BiologicalEvolocumab

    Administered by subcutaneous injection

    Also known as: AMG 145, Repatha

  • DrugPlacebo

    Administered by subcutaneous injection

06

What researchers measure

Primary outcomes

  1. Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

    LDL-C was quantified using the ultracentrifugation method.

    Time frame: Baseline and Week 12

  2. Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

    LDL-C was quantified using the ultracentrifugation method.

    Time frame: Baseline and Week 12

Secondary outcomes

  1. Part A: Change From Baseline in LDL-C at Week 12

    LDL-C was quantified using the ultracentrifugation method.

    Time frame: Baseline and Week 12

  2. Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12

    Time frame: Baseline and Week 12

  3. Part A: Percent Change From Baseline in Apolipoprotein B at Week 12

    Time frame: Baseline and Week 12

  4. Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12

    Time frame: Baseline and Week 12

  5. Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

    Time frame: Baseline and Week 12

  6. Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12

    LDL-C was quantified using the ultracentrifugation method.

    Time frame: Baseline and Week 12

  7. Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12

    Time frame: Baseline and Week 12

  8. Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12

    LDL-C was quantified using the ultracentrifugation method.

    Time frame: Baseline and Weeks 6 and 12

  9. Part B: Percent Change From Baseline in Apolipoprotein B at Week 12

    Time frame: Baseline and Week 12

  10. Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12

    Time frame: Baseline and Weeks 6 and 12

  11. Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12

    Time frame: Baseline and Week 12

  12. Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12

    Time frame: Baseline and Weeks 6 and 12

07

Results

Posted Oct 2, 2015

Participant flow

Male and female adults and adolescents ages ≥ 12 to ≤ 65 years (≥ 12 to ≤ 80 years in Part B) with a diagnosis of homozygous familial hypercholesterolemia (HoFH) were eligible for this study. The first participant enrolled on 05 April 2012 and the last participant enrolled on 08 November 2013.

Participant flow — Overall Study
MilestonePart A: EvolocumabPart B: PlaceboPart B: Evolocumab
Started81733
Received treatment81633
Completed81633
Not completed010
Withdrew: Withdrawal by subject010

Outcome measures

PrimaryPart A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

LDL-C was quantified using the ultracentrifugation method.

Time frame:
Baseline and Week 12
Reported as:
Mean · percent change
Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
percent changePart A: Evolocumab
Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12-16.5 ± 6.7
SecondaryPart A: Change From Baseline in LDL-C at Week 12

LDL-C was quantified using the ultracentrifugation method.

Time frame:
Baseline and Week 12
Reported as:
Mean · mg/dL
Part A: Change From Baseline in LDL-C at Week 12
mg/dLPart A: Evolocumab
Part A: Change From Baseline in LDL-C at Week 12-70.6 ± 32.3
SecondaryPart A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Time frame:
Baseline and Week 12
Reported as:
Mean · percent change
Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
percent changePart A: Evolocumab
Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12-16.6 ± 6.5
SecondaryPart A: Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame:
Baseline and Week 12
Reported as:
Mean · percent change
Part A: Percent Change From Baseline in Apolipoprotein B at Week 12
percent changePart A: Evolocumab
Part A: Percent Change From Baseline in Apolipoprotein B at Week 12-14.9 ± 5.0
SecondaryPart A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time frame:
Baseline and Week 12
Reported as:
Mean · percent change
Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
percent changePart A: Evolocumab
Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12-18.319 ± 6.058
SecondaryPart A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame:
Baseline and Week 12
Reported as:
Mean · percent change
Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
percent changePart A: Evolocumab
Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12-15.65 ± 4.690
SecondaryPart A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12

LDL-C was quantified using the ultracentrifugation method.

Time frame:
Baseline and Week 12
Reported as:
Number · percentage of participants
Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12
percentage of participantsPart A: Evolocumab
Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 1250.0
SecondaryPart A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12
Time frame:
Baseline and Week 12
Reported as:
Mean · ng/mL
Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12
ng/mLPart A: Evolocumab
Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12-151.3 ± 81.7
SecondaryPart B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12

LDL-C was quantified using the ultracentrifugation method.

Time frame:
Baseline and Weeks 6 and 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 124.22 ± 4.56-25.56 ± 3.28
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -29.78 · 95% CI -40.94 to -18.62Placebo is the reference
SecondaryPart B: Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame:
Baseline and Week 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in Apolipoprotein B at Week 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in Apolipoprotein B at Week 123.97 ± 4.74-19.17 ± 3.46
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -23.14 · 95% CI -34.83 to -11.45Placebo is the reference
SecondaryPart B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12
Time frame:
Baseline and Weeks 6 and 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 122.65 ± 4.42-20.24 ± 3.18
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -22.89 · 95% CI -33.72 to -12.05Placebo is the reference
SecondaryPart B: Percent Change From Baseline in Lipoprotein (a) at Week 12
Time frame:
Baseline and Week 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in Lipoprotein (a) at Week 122.43 ± 5.49-9.40 ± 4.07
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects model · p = 0.088 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -11.83 · 95% CI -25.48 to 1.82Placebo is the reference
SecondaryPart B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12
Time frame:
Baseline and Weeks 6 and 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12-1.43 ± 4.78-12.71 ± 3.53
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects · p = 0.088 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -11.27 · 95% CI -23.11 to 0.56Placebo is the reference
PrimaryPart B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

LDL-C was quantified using the ultracentrifugation method.

Time frame:
Baseline and Week 12
Reported as:
Least squares mean · percent change
Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
percent changePart B: PlaceboPart B: Evolocumab
Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 127.88 ± 5.26-23.05 ± 3.78
Statistical analysis
  • Part B: Placebo vs Part B: Evolocumab · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -30.93 · 95% CI -43.86 to -18.00Placebo is the reference

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: OL Evolocumab—0/8 (0%)4/8 (50%)
Part B: DB Placebo—0/16 (0%)10/16 (62.5%)
Part B: DB Evolocumab—0/33 (0%)11/33 (33.3%)
Most frequent other events
Showing 10 of 23
Most frequent other events
EventPart A: OL EvolocumabPart B: DB PlaceboPart B: DB Evolocumab
DyspepsiaGastrointestinal disorders1/80/160/33
NauseaGastrointestinal disorders0/82/160/33
PainGeneral disorders1/80/160/33
BronchitisInfections and infestations1/80/160/33
Rhinitis allergicRespiratory, thoracic and mediastinal disorders1/80/160/33
InfluenzaInfections and infestations0/80/163/33
Upper respiratory tract infectionInfections and infestations0/81/163/33
PalpitationsCardiac disorders0/81/160/33
Abdominal painGastrointestinal disorders0/81/161/33
Abdominal pain upperGastrointestinal disorders0/81/160/33

Baseline characteristics

Age, Continuous
Age, Continuous(years)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Mean34.3 ± 12.432.8 ± 13.730.3 ± 12.431.6 ± 12.7
Sex: Female, Male
Sex: Female, Male(Participants)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Female281626
Male691732
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
American Indian or Alaska Native0000
Asian0112
Black or African American0000
Native Hawaiian or Other Pacific Islander0000
White8162953
Other0033
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Hispanic or Latino0011
Not Hispanic or Latino8173257
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level(participants)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
< 420 mg/dL0112132
≥ 420 mg/dL061218
Missing8008
LDL-C Concentration
LDL-C Concentration(mg/dL)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Part A441.7 ± 113.3NA ± NANA ± NA441.7 ± 113.3
Part BNA ± NA335.8 ± 146.0356.0 ± 134.5349.4 ± 137.2
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration(mg/dL)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Part A470.6 ± 117.8NA ± NANA ± NA470.6 ± 117.8
Part BNA ± NA358.9 ± 149.1374.9 ± 136.9369.7 ± 139.6
Apolipoprotein B Concentration
Apolipoprotein B Concentration(mg/dL)Part A: EvolocumabPart B: PlaceboPart B: EvolocumabTotal
Part A269.1 ± 53.0NA ± NANA ± NA269.1 ± 53.0
Part BNA ± NA208.6 ± 79.5208.3 ± 68.4208.4 ± 71.4

4 further baseline measures are reported on the registry.

08

Study locations

21 sites
  • Research Site
    New York, New York 10032, United States
  • Research Site
    Cincinnati, Ohio 45227, United States
  • Research Site
    Bruxelles, 1200, Belgium
  • Research Site
    La Louvière, 7100, Belgium
  • Research Site
    London, Ontario N6A 5K8, Canada
  • Research Site
    Chicoutimi, Quebec G7H 7K9, Canada
  • Research Site
    Brno, 656 91, Czechia
  • Research Site
    Hradec Kralove, 500 05, Czechia
  • Research Site
    Uherske Hradiste, 686 01, Czechia
  • Research Site
    Dijon, 21000, France
  • Research Site
    Paris Cedex 13, 75651, France
  • Research Site
    New Territories, Hong Kong
  • Research Site
    Pisa, 56124, Italy
  • Research Site
    Beirut, 0000, Lebanon
  • Research Site
    Amsterdam, 1105 AZ, Netherlands
  • Research Site
    Christchurch, 8011, New Zealand
  • Research Site
    Johannesburg, Gauteng 2193, South Africa
  • Research Site
    Observatory, Western Cape 7925, South Africa
  • Research Site
    Cordoba, Andalucía 14004, Spain
  • Research Site
    Lugo, Galicia 27003, Spain
  • Research Site
    Madrid, 28040, Spain
09

References and documents

Publications

  • Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. PubMed 29353350 ↗
  • Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA; TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):341-50. doi: 10.1016/S0140-6736(14)61374-X. Epub 2014 Oct 1. PubMed 25282520 ↗
  • Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013 Nov 5;128(19):2113-20. doi: 10.1161/CIRCULATIONAHA.113.004678. Epub 2013 Sep 6. PubMed 24014831 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 29, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01588496
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
May 1, 2012
Start date
Apr 5, 2012
Primary completion
Jan 31, 2014
Completion
Jan 31, 2014
Results posted
Oct 2, 2015
Last update
Nov 29, 2018

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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