Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects Who Are Intolerant to Statins (SPIRE-SI)
Primary Purpose
Hyperlipidemia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bococizumab (PF-04950615;RN316)
Atorvastatin
Placebo for Bococizumab (PF-04950615;RN316)
Placebo for atorvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Hyperlipidemia focused on measuring Hyperlipidemia, statin intolerance
Eligibility Criteria
Inclusion Criteria:
- Hyperlipidemia
- Statin Intolerant
- Fasting LDL-C > = 70 mg/dL Fasting TG < = 400 mg/dL
Exclusion Criteria:
- Pregnant or breastfeeding females
- Cardiovascular or cerebrovascular event or procedure within 90 days
- Severe or life-threatening adverse events with past use of statins
- Poorly controlled hypertension
Sites / Locations
- Creekside Endocrine Associates, PC
- Bridgeport Hospital
- Watson Clinic Center for Research, Inc. (for Drug Shipment only)
- Cardiovascular Research Center Of South Florida
- St. Johns Center for Clinical Research
- Progressive Medical Research
- East-West Medical Research Institute
- NorthShore University HealthSystem - Evanston Hospital
- Health Care Centers of Illinois Mokena Medical Commons
- Advocate Medical Group Cardiology
- Advocate Medical Group Midwest Heart Specialists
- Prairie Education & Research Cooperative (Administrative)
- Prairie Heart Institute
- St. John's Hospital
- The University of Iowa - College of Public Health - Preventive Intervention Center
- The Iowa Clinic, PC
- University of Kansas Medical Center
- Crescent City Clinical Research Center
- Allina Health System, dba Abbott Northwestern Hospital
- Minneapolis Heart Institute Foundation
- PMG Research of Wilmington, LLC
- Dayton Heart Center
- Clinical and Translational Research Center, Hospital of the University of Pennsylvania
- Perelman Center for Advanced Medicine
- Berks Cardiologists, Ltd.
- PMG Research of Bristol
- PMG Research of Knoxville, LLC
- San Antonio Military Medical Center
- Office of Michelle Zaniewski MD., PA.
- Utah Cardiology, P.C.
- Aspen Clinical Research LLC
- The Medical Arts Health Research Group
- Corunna Medical Research Centre
- The Office of Dr. James Cha
- Kawartha Cardiology Clinical Trials
- Devonshire Clinical Research Inc.
- Ecogene-21
- Omnispec clinical research inc.
- Diex Research Sherbrooke Inc.
- Clinique des maladies lipidiques de Quebec
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Bococizumab (PF-04950615;RN316)
Atorvastatin
Placebo
Arm Description
Bococizumab (PF-04950615;RN316)
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Secondary Outcome Measures
Percent Change From Baseline in Fasting Total Cholesterol (TC) at Weeks 12 and 24
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Weeks 12 and 24
Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Weeks 12 and 24
Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Weeks 12 and 24
Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24
Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12 and 24
Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Weeks 12 and 24
Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Weeks 12 and 24
Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Weeks 12 and 24
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
Absolute Change From Baseline in Fasting Triglycerides (TG) at Week 12
Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12
Absolute Change From Baseline in Lipoprotein (A) (Lp[A]) at Week 12
Absolute Change From Baseline in Fasting Total Cholesterol (TC)/ High Density Lipoprotein Cholesterol (HDL-C) Ratio at Weeks 12 and 24
Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB)/Apolipoprotein A-I (ApoA-I) Ratio at Weeks 12 And 24
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24
Plasma PF-04950615 Concentrations at Weeks 12 and 24
Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.4 micrograms per milliliter [mcg/mL]) to zero. Participants who received PF-04950615 150 mg were evaluable for this outcome measure.
Number of Participants With Adverse Events Related to Type 1 and 3 Hypersensitivity Reactions, Injection Site Reactions, Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
Participants with at least one positive ADA titer greater than or equal to (>=) 6.23 or positive nAb titer >=4.32 were reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint.
Anti-drug Antibody (ADA) and Neutralizing Anti-body (nAb) Titer Level in Participants Who Tested Positive for ADA and nAb Respectively
Titer levels of participants who tested positive for ADA and nAb are reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint.
Percentage of Participants Discontinued Due to Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02135029
Brief Title
Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects Who Are Intolerant to Statins
Acronym
SPIRE-SI
Official Title
A Phase 3, Double-blind, Double-dummy, Randomized, Placebo And Active Controlled, Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Dyslipidemia Who Are Intolerant To Statins
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
June 2014 (Actual)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a multicenter, double blinded, active and placebo controlled randomized clinical trial to demonstrate a superior lipid lowering effect of Bococizumab (PF-04950615; RN316) compared to placebo in subjects who are statin intolerant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipidemia
Keywords
Hyperlipidemia, statin intolerance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
184 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bococizumab (PF-04950615;RN316)
Arm Type
Experimental
Arm Description
Bococizumab (PF-04950615;RN316)
Arm Title
Atorvastatin
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
150 mg every 2 weeks by subcutaneous injection for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
Atorvastatin PO QD
Intervention Type
Other
Intervention Name(s)
Placebo for Bococizumab (PF-04950615;RN316)
Intervention Description
150 mg every 2 weeks by subcutaneous injection for 24 weeks
Intervention Type
Other
Intervention Name(s)
Placebo for atorvastatin
Intervention Description
PO QD
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Fasting Total Cholesterol (TC) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Fasting Triglycerides (TG) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Lipoprotein (A) (Lp[A]) at Week 12
Time Frame
Baseline, Week 12
Title
Absolute Change From Baseline in Fasting Total Cholesterol (TC)/ High Density Lipoprotein Cholesterol (HDL-C) Ratio at Weeks 12 and 24
Time Frame
Baseline, Week 12, 24
Title
Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB)/Apolipoprotein A-I (ApoA-I) Ratio at Weeks 12 And 24
Time Frame
Baseline, Week 12, 24
Title
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24
Time Frame
Week 12, 24
Title
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24
Time Frame
Week 12, 24
Title
Plasma PF-04950615 Concentrations at Weeks 12 and 24
Description
Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.4 micrograms per milliliter [mcg/mL]) to zero. Participants who received PF-04950615 150 mg were evaluable for this outcome measure.
Time Frame
Week 12 and 24
Title
Number of Participants With Adverse Events Related to Type 1 and 3 Hypersensitivity Reactions, Injection Site Reactions, Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations
Time Frame
Baseline (Day 1) up to Week 30
Title
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
Description
Participants with at least one positive ADA titer greater than or equal to (>=) 6.23 or positive nAb titer >=4.32 were reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint.
Time Frame
Baseline up to Week 30
Title
Anti-drug Antibody (ADA) and Neutralizing Anti-body (nAb) Titer Level in Participants Who Tested Positive for ADA and nAb Respectively
Description
Titer levels of participants who tested positive for ADA and nAb are reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint.
Time Frame
Week 4, 12, 24 and 30 (Follow-up)
Title
Percentage of Participants Discontinued Due to Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations
Time Frame
Baseline (Day 1) up to Week 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hyperlipidemia
Statin Intolerant
Fasting LDL-C > = 70 mg/dL Fasting TG < = 400 mg/dL
Exclusion Criteria:
Pregnant or breastfeeding females
Cardiovascular or cerebrovascular event or procedure within 90 days
Severe or life-threatening adverse events with past use of statins
Poorly controlled hypertension
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Creekside Endocrine Associates, PC
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Bridgeport Hospital
City
Bridgeport
State/Province
Connecticut
ZIP/Postal Code
06610
Country
United States
Facility Name
Watson Clinic Center for Research, Inc. (for Drug Shipment only)
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Cardiovascular Research Center Of South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
St. Johns Center for Clinical Research
City
Ponte Vedra
State/Province
Florida
ZIP/Postal Code
32081
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
East-West Medical Research Institute
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
Facility Name
NorthShore University HealthSystem - Evanston Hospital
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Health Care Centers of Illinois Mokena Medical Commons
City
Mokena
State/Province
Illinois
ZIP/Postal Code
60448
Country
United States
Facility Name
Advocate Medical Group Cardiology
City
Normal
State/Province
Illinois
ZIP/Postal Code
61761
Country
United States
Facility Name
Advocate Medical Group Midwest Heart Specialists
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
Prairie Education & Research Cooperative (Administrative)
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62701
Country
United States
Facility Name
Prairie Heart Institute
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62701
Country
United States
Facility Name
St. John's Hospital
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62769
Country
United States
Facility Name
The University of Iowa - College of Public Health - Preventive Intervention Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The Iowa Clinic, PC
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50266
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Crescent City Clinical Research Center
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Allina Health System, dba Abbott Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
PMG Research of Wilmington, LLC
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Dayton Heart Center
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45414
Country
United States
Facility Name
Clinical and Translational Research Center, Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Berks Cardiologists, Ltd.
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
PMG Research of Bristol
City
Bristol
State/Province
Tennessee
ZIP/Postal Code
37620
Country
United States
Facility Name
PMG Research of Knoxville, LLC
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37912
Country
United States
Facility Name
San Antonio Military Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234-6200
Country
United States
Facility Name
Office of Michelle Zaniewski MD., PA.
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
Utah Cardiology, P.C.
City
Layton
State/Province
Utah
ZIP/Postal Code
84041
Country
United States
Facility Name
Aspen Clinical Research LLC
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States
Facility Name
The Medical Arts Health Research Group
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 1V6
Country
Canada
Facility Name
Corunna Medical Research Centre
City
Corunna
State/Province
Ontario
ZIP/Postal Code
N0N 1G0
Country
Canada
Facility Name
The Office of Dr. James Cha
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
L1J 2K1
Country
Canada
Facility Name
Kawartha Cardiology Clinical Trials
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9J 0B2
Country
Canada
Facility Name
Devonshire Clinical Research Inc.
City
Woodstock
State/Province
Ontario
ZIP/Postal Code
N4S 5P5
Country
Canada
Facility Name
Ecogene-21
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Omnispec clinical research inc.
City
Mirabel
State/Province
Quebec
ZIP/Postal Code
J7J 2K8
Country
Canada
Facility Name
Diex Research Sherbrooke Inc.
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 1Z1
Country
Canada
Facility Name
Clinique des maladies lipidiques de Quebec
City
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
28304227
Citation
Ridker PM, Tardif JC, Amarenco P, Duggan W, Glynn RJ, Jukema JW, Kastelein JJP, Kim AM, Koenig W, Nissen S, Revkin J, Rose LM, Santos RD, Schwartz PF, Shear CL, Yunis C; SPIRE Investigators. Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab. N Engl J Med. 2017 Apr 20;376(16):1517-1526. doi: 10.1056/NEJMoa1614062. Epub 2017 Mar 17.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1481030&StudyName=Randomized%20Clinical%20Trial%20of%20RN316%20%28PF-04950615%29%20in%20Subjects%20who%20are%20Intolerant%20to%20Statins
Description
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Learn more about this trial
Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects Who Are Intolerant to Statins
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