Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects With Genetic LDL Disorders

NCT ID: NCT01624142

Last Updated: 2024-05-28

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-01

Study Completion Date

2018-05-11

Brief Summary

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A study to assess the long term safety and tolerability of evolocumab (AMG 145) in adolescents and adults with severe familial hypercholesterolemia.

Detailed Description

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This phase 2/3 open-label extension study was designed to characterize the safety and tolerability of long-term administration of evolocumab to adults and adolescents with severe FH (HoFH or non-HoFH severe FH). Participants not on lipid apheresis at enrollment or within the prior 8 weeks initiated treatment with evolocumab 420 mg once monthly (QM). Participants on lipid apheresis at enrollment initiated treatment with evolocumab 420 mg once every 2 weeks (Q2W). Dose frequency changes (420 mg QM vs 420 mg Q2W) were permitted at week 12, 24, or other visits with Sponsor approval. Participants with \< 5% LDL-C reduction from baseline and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) \< 100 ng/mL could discontinue evolocumab. If serum unbound PCSK9 was ≥ 100 ng/mL with QM dosing, the participant could switch to evolocumab 420 mg Q2W treatment. Participants on apheresis with ≥ 5% LDL-C reduction from baseline and serum unbound PCSK9 \< 100 ng/mL with Q2W treatment could switch to QM dosing.

Participants were to continue to receive open-label evolocumab for up to 5 years or until evolocumab became commercially available in the relevant patient population, whichever occurred first.

Conditions

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Severe Familial Hypercholesterolemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Evolocumab

Participants received 420 mg evolocumab every month (participants not on lipid apheresis) or every 2 weeks (participants on lipid apheresis) for up to 5 years. Participants could switch dosing regimens at week 12 or 24 based on LDL-C and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) levels.

Group Type EXPERIMENTAL

Evolocumab

Intervention Type BIOLOGICAL

Evolocumab was administered by subcutaneous injection either once a month (QM) or once every two weeks (Q2W).

Interventions

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Evolocumab

Evolocumab was administered by subcutaneous injection either once a month (QM) or once every two weeks (Q2W).

Intervention Type BIOLOGICAL

Other Intervention Names

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AMG 145 Repatha

Eligibility Criteria

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Inclusion Criteria

\- Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent protocol and have a diagnosis of familial hypercholesterolemia.

OR

* Have a diagnosis of familial hypercholesterolemia AND
* Males and females ≥ 12 to ≤ 80 years of age
* Stable low-fat diet and lipid-lowering therapies for at least 4 weeks
* Low-density lipoprotein cholesterol (LDL-C) \>= 130 mg/dl (3.4 mmol/L) for subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C \>= 100 mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis patients have no LDL-C entry requirement
* Fasting triglycerides ≤ 400 mg/dL(4.5 mmol/L)
* Body weight of \> 40 kg or greater at screening for subjects less than 18 years of age

Exclusion Criteria

* New York Heart Failure 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 screening
* Planned cardiac surgery or revascularization
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension
Minimum Eligible Age

12 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Los Angeles, California, United States

Site Status

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Nashville, Tennessee, United States

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Hobart, Tasmania, Australia

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Perth, Western Australia, Australia

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Brussels, , Belgium

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La Louvière, , Belgium

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São Paulo, São Paulo, Brazil

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São Paulo, , Brazil

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London, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Uherské Hradiště, , Czechia

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Dijon, , France

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Paris, , France

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Athens, , Greece

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New Territories, , Hong Kong

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Ramat Gan, , Israel

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Cinisello Balsamo (MI), , Italy

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Napoli, , Italy

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Pisa, , Italy

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Kanazawa, Ishikawa-ken, Japan

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Suita, Osaka, Japan

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Beirut, , Lebanon

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Amsterdam, , Netherlands

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Rotterdam, , Netherlands

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Christchurch, , New Zealand

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Johannesburg, Gauteng, South Africa

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Observatory, Western Cape, South Africa

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Córdoba, Andalusia, Spain

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Barcelona, Catalonia, Spain

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A Coruña, Galicia, Spain

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Lugo, Galicia, Spain

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Madrid, , Spain

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Manchester, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada Czechia France Greece Hong Kong Israel Italy Japan Lebanon Netherlands New Zealand South Africa Spain United Kingdom

References

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Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, Couture P, Soran H, Watts GF, Kurtz C, Honarpour N, Tang L, Kasichayanula S, Wasserman SM, Stein EA. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017 Apr;5(4):280-290. doi: 10.1016/S2213-8587(17)30044-X. Epub 2017 Feb 16.

Reference Type BACKGROUND
PMID: 28215937 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29353350 (View on PubMed)

Santos RD, Stein EA, Hovingh GK, Blom DJ, Soran H, Watts GF, Lopez JAG, Bray S, Kurtz CE, Hamer AW, Raal FJ. Long-Term Evolocumab in Patients With Familial Hypercholesterolemia. J Am Coll Cardiol. 2020 Feb 18;75(6):565-574. doi: 10.1016/j.jacc.2019.12.020.

Reference Type BACKGROUND
PMID: 32057369 (View on PubMed)

Raal FJ, Hegele RA, Ruzza A, Lopez JAG, Bhatia AK, Wu J, Wang H, Gaudet D, Wiegman A, Wang J, Santos RD. Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies. Arterioscler Thromb Vasc Biol. 2024 May;44(5):1156-1164. doi: 10.1161/ATVBAHA.123.320268. Epub 2024 Mar 28.

Reference Type BACKGROUND
PMID: 38545781 (View on PubMed)

Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

Reference Type DERIVED
PMID: 33078867 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24014831 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2011-005400-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20110271

Identifier Type: -

Identifier Source: org_study_id

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