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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01968954




Registration number
NCT01968954
Ethics application status
Date submitted
21/10/2013
Date registered
24/10/2013
Date last updated
17/05/2017

Titles & IDs
Public title
Randomized Clinical Trial Of Bococizumab (PF-04950615; RN316) In Subjects With Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events
Scientific 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
Secondary ID [1] 0 0
2013-002642-37
Secondary ID [2] 0 0
B1481019
Universal Trial Number (UTN)
Trial acronym
SPIRE-HR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperlipidemia 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bococizumab (PF-04950615;RN316)
Other interventions - Placebo

Experimental: Bococizumab (PF-04950615;RN316) -

Placebo comparator: Placebo -


Treatment: Drugs: Bococizumab (PF-04950615;RN316)
150 mg every 2 weeks, subcutaneous injection, 12 months

Other interventions: Placebo
subcutaneous injection, every 2 weeks for 12 months
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12
Timepoint [1] 0 0
Baseline, Week 12
Secondary outcome [1] 0 0
Percent Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52
Timepoint [1] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [2] 0 0
Percent Change From Baseline in Non- High Density Lipoprotein-Cholesterol (Non HDL-C) at Week 12, 24 and 52
Timepoint [2] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [3] 0 0
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52
Timepoint [3] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [4] 0 0
Percent Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52
Timepoint [4] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [5] 0 0
Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52
Timepoint [5] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [6] 0 0
Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Primary Hyperlipidemia
Timepoint [6] 0 0
Baseline, Week 12
Secondary outcome [7] 0 0
Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Mixed Dyslipidemia
Timepoint [7] 0 0
Baseline, Week 12
Secondary outcome [8] 0 0
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 24 and 52
Timepoint [8] 0 0
Baseline, Week 24, 52
Secondary outcome [9] 0 0
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 by Triglyceride Cut-off
Timepoint [9] 0 0
Baseline, Week 24, 52
Secondary outcome [10] 0 0
Percent Change From Baseline in Fasting Triglyceride (TG) at Week 12, 24 and 52
Timepoint [10] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [11] 0 0
Percent Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52
Timepoint [11] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [12] 0 0
Percent Change From Baseline in ApolipoproteinA-II (ApoA-II) at Week 12, 24 and 52
Timepoint [12] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [13] 0 0
Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Week 12, 24 and 52
Timepoint [13] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [14] 0 0
Absolute Change From Baseline in Fasting Low Density Lipoprotein-C (LDL-C) at Week 12 by Trigylceride Cut-Off
Timepoint [14] 0 0
Baseline, Week 12
Secondary outcome [15] 0 0
Absolute Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12, 24 and 52
Timepoint [15] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [16] 0 0
Absolute Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52
Timepoint [16] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [17] 0 0
Absolute Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24 and 52
Timepoint [17] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [18] 0 0
Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52
Timepoint [18] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [19] 0 0
Absolute Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52
Timepoint [19] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [20] 0 0
Absolute Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52
Timepoint [20] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [22] 0 0
Absolute Change From Baseline in Ratio of Apolipoprotein B to ApolipoproteinA-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52
Timepoint [22] 0 0
Baseline, Week 12, 24, 52
Secondary outcome [23] 0 0
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
Timepoint [23] 0 0
Week 12, 24 and 52
Secondary outcome [24] 0 0
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
Timepoint [24] 0 0
Week 12, 24 and 52
Secondary outcome [25] 0 0
Plasma PF-04950615 Concentrations at Week 12, 24 and 52
Timepoint [25] 0 0
Week 12, 24, 52
Secondary outcome [26] 0 0
Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions
Timepoint [26] 0 0
Baseline up to the end of study (up to 58 weeks)
Secondary outcome [27] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
Timepoint [27] 0 0
Baseline up to the end of study (up to 58 weeks)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2016
Sample size
Target
Accrual to date
Final
711
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Australian Clinical Research Network - Maroubra
Recruitment hospital [2] 0 0
Core Research Group Pty Ltd - Milton
Recruitment hospital [3] 0 0
The Avenue Cardiovascular Centre - St. Kilda East
Recruitment postcode(s) [1] 0 0
2035 - Maroubra
Recruitment postcode(s) [2] 0 0
4064 - Milton
Recruitment postcode(s) [3] 0 0
3183 - St. Kilda East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Czech Republic
State/province [26] 0 0
Hradec Kralove
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Praha 5
Country [28] 0 0
Czech Republic
State/province [28] 0 0
Zlin
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Hannover
Country [31] 0 0
Germany
State/province [31] 0 0
Ludwigshafen
Country [32] 0 0
Germany
State/province [32] 0 0
Schwerin
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Shatin, NT
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Shatin
Country [35] 0 0
Italy
State/province [35] 0 0
MI
Country [36] 0 0
Italy
State/province [36] 0 0
PA
Country [37] 0 0
Italy
State/province [37] 0 0
RM
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Gyeonggi-do
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Gangwon-Do
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Gwangju
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Suwon
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Ulsan
Country [44] 0 0
Poland
State/province [44] 0 0
Mazowieckie
Country [45] 0 0
Poland
State/province [45] 0 0
Slaskie
Country [46] 0 0
Poland
State/province [46] 0 0
Gdynia
Country [47] 0 0
Poland
State/province [47] 0 0
Lodz
Country [48] 0 0
Poland
State/province [48] 0 0
Opole
Country [49] 0 0
Poland
State/province [49] 0 0
Oswiecim
Country [50] 0 0
Poland
State/province [50] 0 0
Poznan
Country [51] 0 0
Poland
State/province [51] 0 0
Skierniewice
Country [52] 0 0
Poland
State/province [52] 0 0
Sopot
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01968954
Trial related presentations / publications
Chasman DI, Hyde CL, Giulianini F, Danning RD, Wang EQ, Hickling T, Ridker PM, Loomis AK. Genome-wide pharmacogenetics of anti-drug antibody response to bococizumab highlights key residues in HLA DRB1 and DQB1. Sci Rep. 2022 Mar 11;12(1):4266. doi: 10.1038/s41598-022-07997-5.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01968954