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Trial record 1 of 37 for:    SPIRE 2
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The Evaluation of Bococizumab (PF-04950615; RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects (SPIRE-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01975389
Recruitment Status : Terminated (See Detailed Description)
First Posted : November 3, 2013
Results First Posted : June 12, 2018
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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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).

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Drug: bococizumab (PF-04950615) Drug: Placebo Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10564 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 3 Multi Center, Double Blind, Randomized, Placebo Controlled, Parallel Group Evaluation Of The Efficacy, Safety, And Tolerability Of Bococizumab (Pf-04950615), In Reducing The Occurrence Of Major Cardiovascular Events In High Risk Subjects
Actual Study Start Date : October 29, 2013
Actual Primary Completion Date : April 3, 2017
Actual Study Completion Date : April 3, 2017
Arms and Interventions
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Arm Intervention/treatment
Experimental: bococizumab (PF-04950615)
150 mg, every 2 weeks, subcutaneous.
 Drug: bococizumab (PF-04950615)
150 mg, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.
Other Name: RN316
Placebo Comparator: Placebo
Placebo comparator, every 2 weeks, subcutaneous.
 Drug: Placebo
Placebo comparator, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.


Outcome Measures
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Primary Outcome Measures :
  1. Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event [ Time Frame: From 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 :
  1. Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke [ Time Frame: From 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.

  2. 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 Revascularization [ Time Frame: From 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.

  3. Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke [ Time Frame: From 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.

  4. Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization [ Time Frame: From 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.

  5. 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 Angina [ Time Frame: From 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.

  6. Event Rate Per 100 Participant-years for Cardiovascular (CV) Death [ Time Frame: From 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.

  7. Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal) [ Time Frame: 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.

  8. Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI) [ Time Frame: 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.

  9. Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI) [ Time Frame: 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.

  10. Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal) [ Time Frame: 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.

  11. Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology [ Time Frame: From 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.

  12. Event Rate Per 100 Participant-years for Fatal Stroke [ Time Frame: From 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.

  13. Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke [ Time Frame: From 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.

  14. Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina [ Time Frame: From 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.

  15. Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF) [ Time Frame: 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.

  16. Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization [ Time Frame: From 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.

  17. Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG) [ Time Frame: 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.

  18. Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI) [ Time Frame: 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.

  19. Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations [ Time Frame: From 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.

  20. Event Rate Per 100 Participant-years for All-cause Death [ Time Frame: From 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.

  21. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 [ Time Frame: Baseline, Week 14 ]
  22. Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 [ Time Frame: Baseline, Week 14 ]
  23. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement [ Time Frame: Baseline, last post-baseline measurement (any time up to Week 140) ]
  24. Percent Change From Baseline in Lipid Levels at Week 14 [ Time Frame: Baseline, 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.

  25. Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 [ Time Frame: Baseline, Week 14 ]
  26. Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14 [ Time Frame: Baseline, Week 14 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01975389


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] February 12, 2016
Statistical Analysis Plan  [PDF] December 20, 2016

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01975389    
Other Study ID Numbers: B1481038
CV OUTCOMES 2
2013-002795-41 ( EudraCT Number )
First Posted: November 3, 2013    Key Record Dates
Results First Posted: June 12, 2018
Last Update Posted: May 1, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
myocardial infarction
stroke
hyperlipidemia
Additional relevant MeSH terms:
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Cardiovascular Diseases
Bococizumab
Anticholesteremic Agents
Hypolipidemic Agents
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents