NCT01588496

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2012

Geographic Reach
12 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 27, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

April 5, 2012

Completed
26 days until next milestone

First Posted

Study publicly available on registry

May 1, 2012

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2014

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

October 2, 2015

Completed
Last Updated

November 29, 2018

Status Verified

November 1, 2018

Enrollment Period

1.8 years

First QC Date

February 27, 2012

Results QC Date

August 28, 2015

Last Update Submit

November 1, 2018

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

hypercholesterolemiafamilial hypercholesterolemiahomozygous familial hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

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

    LDL-C was quantified using the ultracentrifugation method.

    Baseline and Week 12

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

    LDL-C was quantified using the ultracentrifugation method.

    Baseline and Week 12

Secondary Outcomes (12)

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

    Baseline and Week 12

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

    Baseline and Week 12

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

    Baseline and Week 12

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

    Baseline and Week 12

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

    Baseline and Week 12

  • +7 more secondary outcomes

Study Arms (3)

Part A: Evolocumab

EXPERIMENTAL

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

Biological: Evolocumab

Part B: Evolocumab

EXPERIMENTAL

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

Biological: Evolocumab

Part B: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
Part A: EvolocumabPart B: Evolocumab
PlaceboDRUG

Administered by subcutaneous injection

Part B: Placebo

Eligibility Criteria

Age12 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Research Site

New York, New York, 10032, United States

Location

Research Site

Cincinnati, Ohio, 45227, United States

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

La Louvière, 7100, Belgium

Location

Research Site

London, Ontario, N6A 5K8, Canada

Location

Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Research Site

Brno, 656 91, Czechia

Location

Research Site

Hradec Králové, 500 05, Czechia

Location

Research Site

Uherské Hradiště, 686 01, Czechia

Location

Research Site

Dijon, 21000, France

Location

Research Site

Paris, 75651, France

Location

Research Site

New Territories, Hong Kong

Location

Research Site

Pisa, 56124, Italy

Location

Research Site

Beirut, 0000, Lebanon

Location

Research Site

Amsterdam, 1105 AZ, Netherlands

Location

Research Site

Christchurch, 8011, New Zealand

Location

Research Site

Johannesburg, Gauteng, 2193, South Africa

Location

Research Site

Observatory, Western Cape, 7925, South Africa

Location

Research Site

Córdoba, Andalusia, 14004, Spain

Location

Research Site

Lugo, Galicia, 27003, Spain

Location

Research Site

Madrid, 28040, Spain

Location

Related Publications (3)

  • 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.

    PMID: 29353350BACKGROUND

  • 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.

    PMID: 25282520DERIVED

  • 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.

    PMID: 24014831DERIVED

Related Links

MeSH Terms

Conditions

Homozygous Familial HypercholesterolemiaHypercholesterolemiaHyperlipoproteinemia Type II

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperlipoproteinemiasHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.
866-572-6436

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 27, 2012

First Posted

May 1, 2012

Study Start

April 5, 2012

Primary Completion

January 31, 2014

Study Completion

January 31, 2014

Last Updated

November 29, 2018

Results First Posted

October 2, 2015

Record last verified: 2018-11

Locations

FR(2)ES(3)NZ(1)HK(1)CZ(3)BE(2)LE(1)NL(1)ZA(2)IT(1)CA(2)US(2)