A Phase II Study of the Safety and Efficacy of MPSK3169A in Patients With Coronary Heart Disease or High Risk of Coronary Heart Disease

A Phase II, Randomized, Placebo-Controlled, Double-Blind Study of the Safety and Efficacy of MPSK3169A in Patients With Coronary Heart Disease or High Risk of Coronary Heart Disease

The purpose of this study is to evaluate the safety and cholesterol lowering effects of MPSK3169A when given as subcutaneous (SC) injections over a 24-week period to patients with a high risk of cardiovascular events and LDL-c levels well above goal.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: MPSK3169A; Drug: MPSK3169A; Drug: MPSK3169A; Drug: MPSK3169A; Drug: MPSK3169A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
  • Ontario
    • Sarnia, Ontario, Canada, N7T 4X3
    • Toronto, Ontario, Canada, M9V 4B4
    • Woodstock, Ontario, Canada, N4S 5P5
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
    • Montreal, Quebec, Canada, H2P 2M1
    • Sainte-foy, Quebec, Canada, G1V 4G2
    • St-jerome, Quebec, Canada, J7Z 5T3
    • Trois-Rivières, Quebec, Canada, G8T 7A1
• Czech Republic
  • Hodonin, Czech Republic, 695 01
  • Jičícin, Czech Republic, 50601
  • Marianske Lazne, Czech Republic, 353 01
  • Ostrava - Poruba, Czech Republic, 708 52
  • Rakovník, Czech Republic, 269 01
• Germany
  • Berlin, Germany, 13125
  • Köln, Germany, 50937
• Hungary
  • Komarom, Hungary, 2921
  • Nagykanizsa, Hungary, 8800
  • Nyíregyháza, Hungary, 4400
  • Sopron, Hungary, 9400
• New Zealand
  • Auckland, New Zealand
  • Auckland, New Zealand, 1001
  • Christchurch, New Zealand, 8011
  • Nelson, New Zealand, 7001
  • Tauranga, New Zealand, 3110
• Norway
  • Elverum, Norway, 2401
  • Hamar, Norway, 2317
  • Oslo, Norway, 0027
  • Oslo, Norway, 0160
  • Sandnes, Norway, 4313
• Slovakia
  • Bardejov, Slovakia, 08501
  • Bratislava, Slovakia, 841 07
  • Presov, Slovakia, 080 01
  • Rimavska Sobota, Slovakia, 979 01
• South Africa
  • Cape Town, South Africa, 7505
  • Cape Town, South Africa, 7130
  • Centurion, South Africa, 0157
  • Pretoria, South Africa, 0181
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85395
  • California
    • Carmichael, California, United States, 95608
    • Spring Valley, California, United States, 91978
    • Walnut Creek, California, United States, 94598
    • Wildomar, California, United States, 92595
  • Florida
    • Jacksonville, Florida, United States, 32216
    • Ponte Verde, Florida, United States, 32081
  • Idaho
    • Boise, Idaho, United States, 83704
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Maine
    • Auburn, Maine, United States, 04210
  • Maryland
    • Baltimore, Maryland, United States, 21209
    • Bethesda, Maryland, United States, 20817
  • Missouri
    • St. Louis, Missouri, United States, 63110
  • New York
    • Rochester, New York, United States, 14609
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
  • North Dakota
    • Fargo, North Dakota, United States, 58103
  • Ohio
    • Cincinnati, Ohio, United States, 45212
    • Cincinnati, Ohio, United States, 45219
    • Springdale, Ohio, United States, 45246
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
    • Tulsa, Oklahoma, United States, 74136
  • South Carolina
    • Greer, South Carolina, United States, 29650
    • Mount Pleasant, South Carolina, United States, 29464
    • Spartanburg, South Carolina, United States, 29303
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
  • Tennessee
    • Bristol, Tennessee, United States, 37620
    • Knoxville, Tennessee, United States, 27912
  • Texas
    • Boerne, Texas, United States, 78006
    • Dallas, Texas, United States, 75231
    • Dallas, Texas, United States, 75230
    • Houston, Texas, United States, 77030
  • Virginia
    • Richmond, Virginia, United States, 23294
  • Washington
    • Wenatchee, Washington, United States, 98801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Use of a standard-of-care statin at a stable dose, or intolerance of statins, without use of other lipid modifying therapies
• Fasting LDL cholesterol 90-250 mg/dL on the statin regimen above

And at least one of the following:

• Coronary heart disease (CHD) with a history of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), or prior coronary angiography demonstrating coronary atherosclerosis
• A CHD risk equivalent condition, including diabetes mellitus (type 1 or 2), chronic kidney disease, prior stroke, carotid disease, peripheral arterial disease, or abdominal aortic aneurism
• >/=2 CHD risk factors (age >/= 45 years for men or >/= 55 years for women; smoking; hypertension; low HDL cholesterol; family history of premature CHD) and a high risk of a CV event based on risk estimation systems

Exclusion Criteria:

• Severe congestive heart failure (NYHA Class III-IV) or left ventricular ejection fraction </= 35%
• Recent (within 3 months) MI, unstable angina, stroke, transient ischemic attack, CABG, PCI, hospital admission for heart failure, major surgery, uncontrolled cardiac arrhythmia (other than atrial fibrillation or flutter), or initiation of renal replacement therapy (dialysis)
• Fasting serum triglyceride level >/= 400 mg/dL
• Homozygous familial hypercholesterolemia
• Poorly controlled diabetes mellitus, hypertension or thyroid disease
• Liver or muscle disease, including abnormal test results at screening
• Pregnant or lactating

The above list is not intended to contain all factors relevant to a patient's eligibility for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: B	Drug: MPSK3169A; Dose regimen A, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen E, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen D, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen C, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen B, repeating subcutaneous injections every 4 weeks
EXPERIMENTAL: A	Drug: MPSK3169A; Dose regimen A, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen E, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen D, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen C, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen B, repeating subcutaneous injections every 4 weeks
EXPERIMENTAL: E	Drug: MPSK3169A; Dose regimen A, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen E, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen D, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen C, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen B, repeating subcutaneous injections every 4 weeks
EXPERIMENTAL: C	Drug: MPSK3169A; Dose regimen A, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen E, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen D, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen C, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen B, repeating subcutaneous injections every 4 weeks
EXPERIMENTAL: D	Drug: MPSK3169A; Dose regimen A, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen E, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen D, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen C, repeating subcutaneous injections every 4 weeks; Drug: MPSK3169A; Dose regimen B, repeating subcutaneous injections every 4 weeks
PLACEBO_COMPARATOR: F	Drug: Placebo; Repeating subcutaneous injections of placebo every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change from baseline in LDL-c concentration	at Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute change from baseline in LDL-c concentration for each arm at the nadir for that arm	over the 24 week treatment period
Average value over time of the change in LDL-c (absolute and percent change) for each arm, up to Day 169, weighted by the number of weeks between consecutive LDL-c measurements	up to Day 169
Percent change from baseline in LDL-c concentration at Day 169 and at the nadir for each arm	at Day 169 and over the 24 week treatment period
Percent and absolute change from baseline in LDL-c concentration at all other designated timepoints	at all other designated timepoints
Percent and absolute change from baseline in total cholesterol, non-HDL-c, and apolipoprotein B (ApoB) at Day 169 and at the nadir for each arm	at Day 169 and over the 24 week treatment period

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Baruch A, Mosesova S, Davis JD, Budha N, Vilimovskij A, Kahn R, Peng K, Cowan KJ, Harris LP, Gelzleichter T, Lehrer J, Davis JC Jr, Tingley WG. Effects of RG7652, a Monoclonal Antibody Against PCSK9, on LDL-C, LDL-C Subfractions, and Inflammatory Biomarkers in Patients at High Risk of or With Established Coronary Heart Disease (from the Phase 2 EQUATOR Study). Am J Cardiol. 2017 May 15;119(10):1576-1583. doi: 10.1016/j.amjcard.2017.02.020. Epub 2017 Mar 1. Erratum In: Am J Cardiol. 2018 Feb 12;:

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 29, 2012
• First Posted (ESTIMATE): May 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Dyslipidemia; Hyperlipidemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: GC28210