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

NCT01624142 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 201102712011-005400-15
• Study Type: interventional
• Target: 300
• Locations: 18 countries
• Sites: 44

Brief Summary

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

Conditions

Severe Familial Hypercholesterolemia

Keywords

Hypercholesterolemia; Elevated Cholesterol; High Cholesterol; Homozygous Familial Hypercholesterolemia; PCSK9 mutations; Severe Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  The severity of each adverse event (AE) was graded according to the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) grading scale, where grade 1 = mild AE, grade 2 = moderate AE, grade 3 = severe AE, grade 4 = life-threatening AE and grade 5 = death due to AE.

  From first dose of study drug in Study 20110271 up to 30 days after the last dose or until the end of study date, whichever was earlier; median duration of treatment was 48.7 months.

Secondary Outcomes (7)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)

  Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

• Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

  Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

• Percent Change From Baseline in Lipoprotein (a)

  Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

• Percent Change From Baseline in Apolipoprotein B

  Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

• Percent Change From Baseline in Total Cholesterol/HDL-C Ratio

  Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

Study Arms (1)

Evolocumab

EXPERIMENTAL

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.

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

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

Also known as: AMG 145, Repatha

Evolocumab

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (44)

Research Site

Los Angeles, California, 90048, United States

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New York, New York, 10021, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Cincinnati, Ohio, 45227, United States

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Nashville, Tennessee, 37232, United States

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Hobart, Tasmania, 7000, Australia

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Perth, Western Australia, 6000, Australia

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Brussels, 1200, Belgium

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La Louvière, 7100, Belgium

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São Paulo, São Paulo, 04039-030, Brazil

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São Paulo, 05403-000, Brazil

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London, Ontario, N6A 5K8, Canada

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Chicoutimi, Quebec, G7H 7K9, Canada

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Montreal, Quebec, H2W 1R7, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Québec, Quebec, G1V 4M6, Canada

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Brno, 656 91, Czechia

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Hradec Králové, 500 05, Czechia

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Olomouc, 775 20, Czechia

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Prague, 128 08, Czechia

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Uherské Hradiště, 686 01, Czechia

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Dijon, 21000, France

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Paris, 75651, France

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Athens, 17674, Greece

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New Territories, Hong Kong

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Ramat Gan, 52621, Israel

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Cinisello Balsamo (MI), 20092, Italy

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Napoli, 80131, Italy

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Pisa, 56124, Italy

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Kanazawa, Ishikawa-ken, 920-8641, Japan

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Suita, Osaka, 565-8565, Japan

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Beirut, 0000, Lebanon

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Amsterdam, 1105 AZ, Netherlands

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Rotterdam, 3045 PM, Netherlands

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Christchurch, 8011, New Zealand

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Johannesburg, Gauteng, 2193, South Africa

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Observatory, Western Cape, 7925, South Africa

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Córdoba, Andalusia, 14004, Spain

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Barcelona, Catalonia, 08036, Spain

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A Coruña, Galicia, 15001, Spain

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Lugo, Galicia, 27003, Spain

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Madrid, 28040, Spain

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Manchester, M13 9WL, United Kingdom

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Related Publications (6)

• 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.

  PMID: 28215937 BACKGROUND

• 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: 29353350 BACKGROUND

• 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.

  PMID: 32057369 BACKGROUND

• 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.

  PMID: 38545781 BACKGROUND

• 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.

  PMID: 33078867 DERIVED

• 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: 24014831 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia; Homozygous Familial Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 20, 2012
• Study Start: June 1, 2012
• Primary Completion: May 11, 2018
• Study Completion: May 11, 2018
• Last Updated: May 28, 2024
• Results First Posted: January 28, 2019

Record last verified: 2024-05

Locations

ZA (2); CZ (5); NL (2); HK (1); GR (1); US (6); JP (2); BR (2); IT (3); CA (5); ES (5); FR (2); NZ (1); IL (1); GB (1); LE (1); AU (2); BE (2)