Randomized Clinical Trial Of Bococizumab (PF-04950615; RN316) In Subjects With Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events (SPIRE-HR)

• ClinicalTrials.gov Identifier: NCT01968954
• Recruitment Status: Completed
• First Posted: October 24, 2013
• Results First Posted: May 17, 2017
• Last Update Posted: May 17, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 21, 2013
• First Posted Date: October 24, 2013
• Results First Submitted Date: April 6, 2017
• Results First Posted Date: May 17, 2017
• Last Update Posted Date: May 17, 2017
• Study Start Date: October 2013
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 6, 2017): Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]

Original Primary Outcome Measures (submitted: October 21, 2013)

Percent Change from Baseline in LDL-C at Week 12 [ Time Frame: 12 weeks ]

Low Density Lipoprotein (LDL) blood concentrations.

Current Secondary Outcome Measures (submitted: April 6, 2017)

• Percent Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Non- High Density Lipoprotein-Cholesterol (Non HDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Primary Hyperlipidemia [ Time Frame: Baseline, Week 12 ]
  Participants with primary hyperlipidemia are defined as participants with triglycerides (TG) level less than (<) 200 milligram per decilitre (mg/dL) (2.26 millimoles per litre [mmol/L]) at pre-randomization.
• Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Mixed Dyslipidemia [ Time Frame: Baseline, Week 12 ]
  Participants with mixed dyslipidemia are defined as TG level greater than or equal to (>=) 200 mg/dL (2.26 mmol/L) at pre-randomization.
• Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 by Triglyceride Cut-off [ Time Frame: Baseline, Week 24, 52 ]
  Percent change from baseline in fasting LDL-C among participants with TG cut-off of <200 mg/dL and >=200 mg/dL (2.26 mmol/L) were reported in this outcome measure.
• Percent Change From Baseline in Fasting Triglyceride (TG) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in ApolipoproteinA-II (ApoA-II) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Fasting Low Density Lipoprotein-C (LDL-C) at Week 12 by Trigylceride Cut-Off [ Time Frame: Baseline, Week 12 ]
  Absolute change from baseline among participants with TG cut-off of <200 mg/dL and >=200 mg/dL (2.26 mmol/L) were reported in this outcome measure.
• Absolute Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Ratio of Fasting Total Cholesterol to High Density Lipoprotein-Cholesterol (TC/HDL-C Ratio) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Ratio of Apolipoprotein B to ApolipoproteinA-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percentage of Participants Achieving Fasting Low Density Lipoprotein-Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (2.59 Millimoles Per Litre) at Week 12, 24 and 52 [ Time Frame: Week 12, 24 and 52 ]
• Percentage of Participants Achieving Fasting Low Density Lipoprotein-Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (1.81 Millimoles Per Litre) at Week 12, 24 and 52 [ Time Frame: Week 12, 24 and 52 ]
• Plasma PF-04950615 Concentrations at Week 12, 24 and 52 [ Time Frame: Week 12, 24, 52 ]
• Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions [ Time Frame: Baseline up to the end of study (up to 58 weeks) ]
  Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then included glomerulonephritis as well. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, pain, pruritus and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure.
• Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) [ Time Frame: Baseline up to the end of study (up to 58 weeks) ]
  Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. Participants with their ADA titer >=6.23 were considered to be ADA positive and participants with their nAb titer >=1.58 were considered to be nAb positive.

Original Secondary Outcome Measures (submitted: October 21, 2013)

• Change from Baseline in Lipid Parameters at Week 12 [ Time Frame: 12 weeks ]
  Mean Total Cholesterol (TC), Apolipoprotein B, non-HDL-C, Low Density Lipoprotein (LDL) by TG level, High Density Lipoprotein (HDL), Triglycerides (TG), ApoA-I, ApoA-II blood concentrations.
• Change from Baseline in Lipid Parameters at Week 24 [ Time Frame: 24 weeks ]
  Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL) and LDL by TG, lipoprotein (a), and High Density Lipoprotein (HDL), TG, ApoA-I, ApoA-II, blood concentrations.
• Change from Baseline in Lipid Parameters at Week 52 [ Time Frame: 52 weeks ]
  Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL) and LDL by TG, lipoprotein (a), and High Density Lipoprotein (HDL), TG, ApoA-I, ApoA-II blood concentrations.
• Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL [ Time Frame: 12 weeks ]
  Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL
• Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL [ Time Frame: 24 weeks ]
  Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL
• Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL [ Time Frame: 52 weeks ]
  Proportion of Subjects Achieving Fasting LDL-C <= 100 mg/dL and <=70 mg/dL
• Plasma PF-04950615 concentration [ Time Frame: 12 weeks ]
  Plasma PF-04950615 concentration
• Plasma PF-04950615 concentration [ Time Frame: 24 weeks ]
  Plasma PF-04950615 concentration
• Plasma PF-04950615 concentration [ Time Frame: 52 weeks ]
  Plasma PF-04950615 concentration

Current Other Pre-specified Outcome Measures (submitted: April 6, 2017)

• Absolute Change From Baseline in Triglyceride (TG) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in ApolipoproteinA-II (ApoA-II) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Randomized Clinical Trial Of Bococizumab (PF-04950615; RN316) In Subjects With Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events
• Official Title: A Phase 3 Double-blind,Randomized, Placebo-controlled,Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events
• Brief Summary: This study is a multicenter, randomized study in subjects with high cholesterol receiving highly effective statins to assess the efficacy, safety and tolerability of Bococizumab (PF-04950615;RN316) to lower LDL-C.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hyperlipidemia

Intervention

• Drug: Bococizumab (PF-04950615;RN316)
  150 mg every 2 weeks, subcutaneous injection, 12 months
  Other Name: RN316
• Other: Placebo
  subcutaneous injection, every 2 weeks for 12 months

Study Arms

• Experimental: Bococizumab (PF-04950615;RN316)
  Intervention: Drug: Bococizumab (PF-04950615;RN316)
• Placebo Comparator: Placebo
  Intervention: Other: Placebo

Publications *

• Wang EQ, Bukowski JF, Yunis C, Shear CL, Ridker PM, Schwartz PF, Baltrukonis D. Assessing the Potential Risk of Cross-Reactivity Between Anti-Bococizumab Antibodies and Other Anti-PCSK9 Monoclonal Antibodies. BioDrugs. 2019 Oct;33(5):571-579. doi: 10.1007/s40259-019-00375-0.
• Ridker PM, Rose LM, Kastelein JJP, Santos RD, Wei C, Revkin J, Yunis C, Tardif JC, Shear CL; Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Investigators. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab. J Clin Lipidol. 2018 Jul - Aug;12(4):958-965. doi: 10.1016/j.jacl.2018.03.088. Epub 2018 Apr 3.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 16, 2017): 711
• Original Estimated Enrollment (submitted: October 21, 2013): 600
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Treated with a statin.
• Fasting LDL-C > 70 mg/dL and triglyceride <=400 mg/dL.
• High or very high risk of incurring a cardiovascular event.

Exclusion Criteria:

• Pregnant or breastfeeding females.
• Cardiovascular or cerebrovascular event of procedures during the past 30 days.
• Congestive heart failure NYHA class IV.
• Poorly controlled hypertension.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czech Republic, Germany, Hong Kong, Italy, Korea, Republic of, Poland, United States
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT01968954
• Other Study ID Numbers: B1481019; 2013-002642-37 ( EudraCT Number ); SPIRE-HR ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2017