Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3

NCT01984424 | Completed Phase 3 Results DMC

• 2 other identifiers: 201203322013-000935-29
• Study Type: interventional
• Target: 511
• Locations: 13 countries
• Sites: 58

Brief Summary

The primary objective of this study was to evaluate the effect of 24 weeks of evolocumab administered subcutaneously (SC) every month, compared with ezetimibe, on low-density lipoprotein cholesterol (LDL-C) levels in adults with high cholesterol who are unable to tolerate an effective dose of a statin due to muscle-related side effects (MRSE).

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 the Mean of Weeks 22 and 24

  Baseline and weeks 22 and 24

• Percent Change From Baseline in LDL-C at Week 24

  Baseline and week 24

Secondary Outcomes (22)

• Change From Baseline in LDL-C at the Mean of Weeks 22 and 24

  Baselie and weeks 22 and 24

• Change From Baseline in LDL-C at Week 24

  Baseline and week 24

• Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL

  Weeks 22 and 24

• Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL

  Week 24

• Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24

  Baseline and weeks 22 and 24

Study Arms (5)

Part A: Atorvastatin 20 mg => Placebo

OTHER

Participants received atorvastatin 20 mg orally for 10 weeks (period 1) followed by placebo orally for 10 weeks (period 2), separated by a 2-week washout period.

Drug: Atorvastatin; Drug: Placebo to Atorvastatin

Part A: Placebo => Atorvastatin 20 mg

OTHER

Participants received placebo orally for 10 weeks (period 1) followed by atorvastatin 20 mg orally for 10 weeks (period 2), separated by a 2-week washout period.

Drug: Atorvastatin; Drug: Placebo to Atorvastatin

Part B: Ezetimibe

ACTIVE COMPARATOR

Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.

Drug: Ezetimibe; Other: Placebo to Evolocumab

Part B: Evolocumab

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Other: Placebo to Ezetimibe; Drug: Evolocumab

Part C: Open-label Evolocumab

EXPERIMENTAL

Participants who completed part B and were eligible to proceed to open-label extension part C and could choose quarterly between evolocumab 420 mg once a month or evolocumab 140 mg every 2 weeks for up to 2 years.

Drug: Evolocumab

Interventions

Atorvastatin DRUG

Atorvastatin was supplied as over-encapsulated 20 mg tablets

Also known as: Lipitor

Part A: Atorvastatin 20 mg => Placebo; Part A: Placebo => Atorvastatin 20 mg

Placebo to Atorvastatin DRUG

Placebo matching to atorvastatin supplied as over-encapsulated tablets

Part A: Atorvastatin 20 mg => Placebo; Part A: Placebo => Atorvastatin 20 mg

Placebo to Ezetimibe OTHER

Placebo matching to Ezetimibe supplied as over-encapsulated tablets.

Part B: Evolocumab

Ezetimibe DRUG

Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.

Also known as: Zetia

Part B: Ezetimibe

Placebo to Evolocumab OTHER

Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)

Part B: Ezetimibe

Evolocumab DRUG

Evolocumab supplied as single-use prefilled autoinjector/pen(s)

Also known as: Repatha

Part B: Evolocumab; Part C: Open-label Evolocumab

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
• Subject not at LDL-C goal
• History of statin intolerance
• Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks
• Fasting triglycerides ≤ 400 mg/dL

You may not qualify if:

• 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 (58)

Research Site

Beverly Hills, California, 90211, United States

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Huntington Beach, California, 92648, United States

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Los Angeles, California, 90048, United States

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San Pedro, California, 90732, United States

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Atlanta, Georgia, 30322, United States

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Sterling, Illinois, 61081, United States

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Kansas City, Kansas, 66160, United States

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Baltimore, Maryland, 21201, United States

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Towson, Maryland, 21204, United States

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Ann Arbor, Michigan, 48106, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10029, United States

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Durham, North Carolina, 27710, United States

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Cleveland, Ohio, 44195, United States

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York, Pennsylvania, 17405, United States

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Charleston, South Carolina, 29425, United States

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Houston, Texas, 77030, United States

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Camperdown, New South Wales, 2015, Australia

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Woolloongabba, Queensland, 4102, Australia

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Ashford, South Australia, 5035, Australia

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Vancouver, British Columbia, V5Z 1M9, Canada

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Hamilton, Ontario, L8L 2X2, Canada

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London, Ontario, N6A 4V2, Canada

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Peterborough, Ontario, K9J 0B2, Canada

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Montreal, Quebec, H2W 1R7, Canada

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Québec, Quebec, G1V 4M6, Canada

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Saint-Charles-Borromée, Quebec, J6E 6J2, Canada

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Hradec Králové, 500 05, Czechia

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Prague, 128 08, Czechia

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Prague, 140 21, Czechia

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Aarhus N, 8200, Denmark

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Glostrup Municipality, 2600, Denmark

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Nantes, 44093, France

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Paris, 75651, France

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Vénissieux, 69200, France

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Berlin, 13353, Germany

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Cologne, 50937, Germany

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München, 80638, Germany

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Bologna, 40138, Italy

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Cagliari, 09134, Italy

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Cinisello Balsamo (MI), 20092, Italy

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Ferrara, 44100, Italy

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Perugia, 06129, Italy

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Pisa, 56124, Italy

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Amsterdam, 1105 AZ, Netherlands

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Rotterdam, 3045 PM, Netherlands

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Zwijndrecht, 3331 LZ, Netherlands

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Christchurch, 8011, New Zealand

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Ålesund, 6003, Norway

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Oslo, 0373, Norway

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Johannesburg, Gauteng, 2157, 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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Birmingham, B15 2TH, United Kingdom

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Glasgow, G12 8TA, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (3)

• Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.

  PMID: 30073585 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

• Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceska R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA; GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016 Apr 19;315(15):1580-90. doi: 10.1001/jama.2016.3608.

  PMID: 27039291 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipidemias; Hypercholesterolemia

Interventions

Atorvastatin; Ezetimibe; evolocumab

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines

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: November 8, 2013
• First Posted: November 14, 2013
• Study Start: December 10, 2013
• Primary Completion: November 10, 2015
• Study Completion: November 21, 2017
• Last Updated: November 29, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-11

Locations

NL (3); NO (2); ZA (4); FR (3); IT (6); CZ (3); US (18); GB (3); NZ (1); DE (3); AU (3); CA (7); DK (2)