Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects Who Are Intolerant to Statins (SPIRE-SI)

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Bococizumab (PF-04950615;RN316); Drug: Atorvastatin; Other: Placebo for Bococizumab (PF-04950615;RN316); Other: Placebo for atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4W2
    • Clinique des Maladies Lipidiques de Québec
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1V6
      • The Medical Arts Health Research Group
  • Ontario
    • Corunna, Ontario, Canada, N0N 1G0
      • Corunna Medical Research Centre
    • Oshawa, Ontario, Canada, L1J 2K1
      • The Office of Dr. James Cha
    • Peterborough, Ontario, Canada, K9J 0B2
      • Kawartha Cardiology Clinical Trials
    • Woodstock, Ontario, Canada, N4S 5P5
      • Devonshire Clinical Research Inc.
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Mirabel, Quebec, Canada, J7J 2K8
      • Omnispec clinical research inc.
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Research Sherbrooke Inc.
• United States
  • Colorado
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates, PC
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
  • Florida
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Research, Inc. (for Drug Shipment only)
    • Miami, Florida, United States, 33173
      • Cardiovascular Research Center of South Florida
    • Ponte Vedra, Florida, United States, 32081
      • St. Johns Center for Clinical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem - Evanston Hospital
    • Mokena, Illinois, United States, 60448
      • Health Care Centers of Illinois Mokena Medical Commons
    • Normal, Illinois, United States, 61761
      • Advocate Medical Group Cardiology
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group Midwest Heart Specialists
    • Springfield, Illinois, United States, 62769
      • St. John's Hospital
    • Springfield, Illinois, United States, 62701
      • Prairie Heart Institute
    • Springfield, Illinois, United States, 62701
      • Prairie Education & Research Cooperative (Administrative)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa - College of Public Health - Preventive Intervention Center
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic, PC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System, dba Abbott Northwestern Hospital
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Dayton Heart Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical and Translational Research Center, Hospital of the University of Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Berks Cardiologists, Ltd.
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research of Bristol
    • Knoxville, Tennessee, United States, 37912
      • PMG Research of Knoxville, LLC
  • Texas
    • Fort Sam Houston, Texas, United States, 78234-6200
      • San Antonio Military Medical Center
    • Houston, Texas, United States, 77090
      • Office of Michelle Zaniewski MD., PA.
  • Utah
    • Layton, Utah, United States, 84041
      • Utah Cardiology, P.C.
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo for Bococizumab (PF-04950615;RN316); 150 mg every 2 weeks by subcutaneous injection for 24 weeks; Other: Placebo for atorvastatin; PO QD
Active Comparator: Atorvastatin	Drug: Atorvastatin; Atorvastatin PO QD
Experimental: Bococizumab (PF-04950615;RN316)	Drug: Bococizumab (PF-04950615;RN316); 150 mg every 2 weeks by subcutaneous injection for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12		Baseline, Week 12
Percent Change From Baseline in Fasting Total Cholesterol (TC) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24		Baseline, Week 24
Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Weeks 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Weeks 12 and 24		Baseline, Week 12, 24
Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Fasting Triglycerides (TG) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Lipoprotein (A) (Lp[A]) at Week 12		Baseline, Week 12
Absolute Change From Baseline in Fasting Total Cholesterol (TC)/ High Density Lipoprotein Cholesterol (HDL-C) Ratio at Weeks 12 and 24		Baseline, Week 12, 24
Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB)/Apolipoprotein A-I (ApoA-I) Ratio at Weeks 12 And 24		Baseline, Week 12, 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		Week 12, 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		Week 12, 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.	Week 12 and 24
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		Baseline (Day 1) up to Week 30
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.	Baseline up to Week 30
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.	Week 4, 12, 24 and 30 (Follow-up)
Percentage of Participants Discontinued Due to Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations		Baseline (Day 1) up to Week 30

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 7, 2014
• First Submitted That Met QC Criteria: May 7, 2014
• First Posted (Estimate): May 9, 2014

Study Record Updates

• Last Update Posted (Actual): December 14, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Hyperlipidemia; statin intolerance
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Bococizumab
• Other Study ID Numbers: B1481030; STATIN INTOLERANT; SPIRE-SI (Other Identifier: Alias Study Number)