Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2

NCT01763918 | Completed Phase 3 Results DMC

• 2 other identifiers: 201101172012-001365-32
• Study Type: interventional
• Target: 331
• Locations: 14 countries
• Sites: 39

Brief Summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

Conditions

Hyperlipidemia

Keywords

High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in LDL-C at Week 12

  Baseline and Week 12

• Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

Secondary Outcomes (20)

• Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

• Change From Baseline in LDL-C at Week 12

  Baseline and Week 12

• Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)

  Weeks 10 and 12

• Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12

  Week 12

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

Study Arms (4)

Placebo Q2W

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.

Drug: Placebo

Placebo QM

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.

Drug: Placebo

Evolocumab Q2W

EXPERIMENTAL

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.

Biological: Evolocumab

Evolocumab QM

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab Q2W; Evolocumab QM

Placebo DRUG

Administered by subcutaneous injection

Placebo Q2W; Placebo QM

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 to ≤ 80 years of age
• Diagnosis of heterozygous familial hypercholesterolemia
• On a stable dose of an approved statin and lipid regulating medication
• Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L)
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

You may not qualify if:

• Homozygous familial hypercholesterolemia
• LDL or plasma apheresis
• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Type 1 diabetes, poorly controlled type 2 diabetes
• Uncontrolled hypothyroidism or hyperthyroidism

Sponsors & Collaborators

• Amgen: lead

Study Sites (39)

Research Site

Scottsdale, Arizona, 85258, United States

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Cincinnati, Ohio, 45227, United States

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Camperdown, New South Wales, 2015, Australia

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Perth, Western Australia, 6000, Australia

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Vancouver, British Columbia, V6Z 1Y6, Canada

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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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Bron, 69677, France

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Nantes, 44093, France

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Paris, 75651, France

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Cologne, 50937, Germany

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New Territories, Hong Kong

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Amersfoort, 3813 TZ, Netherlands

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Amsterdam, 1091 AC, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Gouda, 2803 HH, Netherlands

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Groningen, 9713 GZ, Netherlands

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Hoorn, 1625 HV, Netherlands

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Tilburg, 5022 GC, Netherlands

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Utrecht, 3584 CX, Netherlands

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Christchurch, 8011, New Zealand

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Oslo, 0373, Norway

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Johannesburg, Gauteng, 2193, South Africa

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Midrand, Gauteng, 1685, South Africa

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Observatory, Western Cape, 7925, South Africa

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Parow, Western Cape, 7505, South Africa

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Córdoba, Andalusia, 14004, Spain

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Zaragoza, Aragon, 50009, Spain

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Reus, Catalonia, 43204, Spain

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Madrid, 28040, Spain

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Stockholm, 111 35, Sweden

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Stockholm, 141 86, Sweden

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Reinach, 4153, Switzerland

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Coventry, CV2 2DX, United Kingdom

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London, SE1 7EH, United Kingdom

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London, W6 8RF, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Related Publications (7)

• Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

  PMID: 28249876 BACKGROUND

• Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.

  PMID: 29736889 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

• Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.

  PMID: 29768954 BACKGROUND

• Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, Langslet G, Scott R, Olsson AG, Sullivan D, Hovingh GK, Cariou B, Gouni-Berthold I, Somaratne R, Bridges I, Scott R, Wasserman SM, Gaudet D; RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):331-40. doi: 10.1016/S0140-6736(14)61399-4. Epub 2014 Oct 1.

  PMID: 25282519 BACKGROUND

• Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.

  PMID: 30755061 BACKGROUND

• Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.

  PMID: 30120772 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipidemias; Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional 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 3
• 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: January 7, 2013
• First Posted: January 9, 2013
• Study Start: February 7, 2013
• Primary Completion: November 27, 2013
• Study Completion: December 19, 2013
• Last Updated: June 17, 2019
• Results First Posted: December 22, 2015

Record last verified: 2019-06

Locations

CA (5); US (2); HK (1); NL (8); FR (3); NO (1); DE (1); NZ (1); ZA (4); ES (4); GB (4); AU (2); SE (2); CH (1)