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The Evaluation of Bococizumab (PF-04950615; RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects

Phase 3
Terminated
Conditions
Cardiovascular Disease
Interventions
Registration Number
NCT01975389
Lead Sponsor
Pfizer
Brief Summary

This study evaluates the PCSK9 inhibitor, Bococizumab (PF-04950615;RN316), compared to placebo, in reducing the occurrrence of major cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and unstable angina requiring urgent revascularization in high risk subjects who are receiving background lipid lowering therapy and have cholesterol laboratory values of LDL-C \>/= 100 mg/dL (2.6 mmol/L) or non-HDL-C \>/=130 mg/dL (3.4 mmol/L).

Detailed Description

The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. These indicated that bococizumab was not likely to provide value to patients, physicians, or shareholders. The decision was not based on a recommendation by the independent Data Monitoring Committee to stop the program.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
10564
Inclusion Criteria
  • Must be on background lipid lowering treatment.
  • Must be at high risk of a CV event.
  • Must have an LDL C >/=100 mg/dL (2.6 mmol/L) OR non HDL C >/=130 mg/dL (3.4 mmol/L).
Exclusion Criteria
  • Planned coronary (PCI or CABG) or other arterial revascularization.
  • New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging.
  • Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis.
  • History of hemorrhagic stroke.
  • Prior exposure to bococizumab or other investigational PCSK9 inhibitor.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
bococizumab (PF-04950615)bococizumab (PF-04950615)150 mg, every 2 weeks, subcutaneous.
PlaceboPlaceboPlacebo comparator, every 2 weeks, subcutaneous.
Primary Outcome Measures
NameTimeMethod
Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) EventFrom baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of major CV event (adjudicated by Adjudication Committee) was reported. Major CV event was defined as any of the following: CV death \[defined as sudden cardiac death, fatal myocardial infarction (MI), death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes\] non-fatal MI, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization. Event rate was calculated as the number of events per 100 participant-years at risk.

Secondary Outcome Measures
NameTimeMethod
Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal StrokeFrom baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of composite endpoint of CV Death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent RevascularizationFrom baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal StrokeFrom baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal)From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any EtiologyFrom baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) of any etiology (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) of any etiology (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for Fatal StrokeFrom baseline until the date of adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for occurrence of fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Non-fatal StrokeFrom baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of non-fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable AnginaFrom baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF)From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for CHF (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of hospitalization for CHF (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Coronary RevascularizationFrom baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of coronary revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of CABG (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent RevascularizationFrom baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable AnginaFrom baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for Cardiovascular (CV) DeathFrom baseline until the date of adjudicated and confirmed occurrence of CV death (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for occurrence of CV death (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal)From baseline until the date of first adjudicated and confirmed occurrence of any myocardial infarction (fatal or non-fatal) (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of any myocardial infarction (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI)From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for occurrence of fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI)From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of non-fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14Baseline, Week 14
Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14Baseline, Week 14
Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI)From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of PCI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for First Occurrence of Any Arterial RevascularizationsFrom baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of any arterial revascularizations (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Event Rate Per 100 Participant-years for All-cause DeathFrom baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for occurrence of all-cause death (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.

Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14Baseline, Week 14
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14Baseline, Week 14
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline MeasurementBaseline, last post-baseline measurement (any time up to Week 140)
Percent Change From Baseline in Lipid Levels at Week 14Baseline, Week 14

Lipids included non-high density lipoprotein cholesterol (non-HDL-C), very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C, apolipoprotein A-I (Apo A-I) and total cholesterol.

Trial Locations

Locations (1554)

Ernest Hendrix, MD, PC

🇺🇸

Athens, Alabama, United States

North Alabama Research Center, LLC

🇺🇸

Athens, Alabama, United States

Central Alabama Research

🇺🇸

Birmingham, Alabama, United States

Clinical Research Advantage, Inc./Simon Williamson Clinic

🇺🇸

Birmingham, Alabama, United States

The Kirklin Clinic

🇺🇸

Birmingham, Alabama, United States

Birmingham Heart Clinic, P.C.

🇺🇸

Birmingham, Alabama, United States

University of Alabama at Birmingham (Drug Shipment)

🇺🇸

Birmingham, Alabama, United States

Appalachian Cardiovascular Associates

🇺🇸

Fort Payne, Alabama, United States

Fundamental Research, LLC

🇺🇸

Gulf Shores, Alabama, United States

Avant Research Associates, LLC

🇺🇸

Crowley, Louisiana, United States

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Ernest Hendrix, MD, PC
🇺🇸Athens, Alabama, United States

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