Clinical trial NCT01968954: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipidemia
Keywords: mixed dyslipidemia
high risk of cardiovascular events
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-10-24
Enrollment: 711
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percent Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Non- High Density Lipoprotein-Cholesterol (Non HDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Primary Hyperlipidemia
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Mixed Dyslipidemia
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 by Triglyceride Cut-off
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Fasting Triglyceride (TG) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in ApolipoproteinA-II (ApoA-II) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Fasting Low Density Lipoprotein-C (LDL-C) at Week 12 by Trigylceride Cut-Off
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: 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
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in Ratio of Apolipoprotein B to ApolipoproteinA-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: 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
timeFrame: Week 12, 24 and 52
measure: 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
timeFrame: Week 12, 24 and 52
measure: Plasma PF-04950615 Concentrations at Week 12, 24 and 52
timeFrame: Week 12, 24, 52
measure: Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions
timeFrame: Baseline up to the end of study (up to 58 weeks)
measure: Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
timeFrame: Baseline up to the end of study (up to 58 weeks)
Other outcomes:
measure: Absolute Change From Baseline in Triglyceride (TG) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Absolute Change From Baseline in ApolipoproteinA-II (ApoA-II) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Birmingham
country: United States
facility: Cardiovascular Associates of the Southeast, LLC
state: Alabama
city: Tucson
country: United States
facility: Southwest Heart Group
state: Arizona
city: Tucson
country: United States
facility: ARA-Arizona Research Associates
state: Arizona
city: Encinitas
country: United States
facility: Diagnamics, Inc.
state: California
city: Encinitas
country: United States
facility: Encompass Clinical Research North Coast
state: California
city: Fountain Valley
country: United States
facility: MD Studies, Inc.
state: California
city: Laguna Hills
country: United States
facility: Alliance Research Centers
state: California
city: Laguna Hills
country: United States
facility: Prime Care Clinical Research
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: San Diego
country: United States
facility: San Diego Family Care
state: California
city: Stockton
country: United States
facility: St. Joseph's Medical Associates
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Vista
country: United States
facility: Clinical Research Advantage, Inc./Cassidy Medical Group - Vista
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: Expresscare Clinical Research
state: Colorado
city: Norwalk
country: United States
facility: Soundview Medical Associates
state: Connecticut
city: Hialeah
country: United States
facility: Eastern Research, Inc.
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC at Northeast Florida Endocrine & Diabetes Associates
state: Florida
city: Jacksonville
country: United States
facility: Care Partners Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Prestige Clinical Research Center Inc
state: Florida
city: New Smyrna Beach
country: United States
facility: Edgewater Medical Research
state: Florida
city: Tampa
country: United States
facility: Gulfcoast Medical Research Center, LLC
state: Florida
city: Savannah
country: United States
facility: Fellows Research Alliance, Inc.
state: Georgia
city: Savannah
country: United States
facility: SouthCoast Medical Group
state: Georgia
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Anderson
country: United States
facility: Comunity Clinical Research Center
state: Indiana
city: Avon
country: United States
facility: American Health Network of Indiana, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Eunice
country: United States
facility: Horizon Research Group of Opelousas, LLC
state: Louisiana
city: Eunice
country: United States
facility: Internal Medicine Associates
state: Louisiana
city: Quincy
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health System, dba Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of MN, Lillehei Clinical Trials Unit
state: Minnesota
city: Missoula
country: United States
facility: Montana Medical Research Inc.
state: Montana
city: Cary
country: United States
facility: PMG Research of Raleigh, LLC d/b/a PMG Research of Cary
state: North Carolina
city: Winston Salem
country: United States
facility: Clinical Trials of America, Inc.
state: North Carolina
city: Akron
country: United States
facility: Radiant Research, Inc
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Perrysburg
country: United States
facility: The Office of Daniel G. Williams, MD
state: Ohio
city: Willoughby
country: United States
facility: Great Lakes Medical Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research LLC
state: Oklahoma
city: Ashland
country: United States
facility: Integrated Medical Research, PC
state: Oregon
city: Portland
country: United States
facility: Columbia Research Group, Inc.
state: Oregon
city: Harleysville
country: United States
facility: Harleysville Medical Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine Heart & Vascular Center
state: Pennsylvania
city: Wyomissing
country: United States
facility: Berks Cardiologists, Ltd.
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Research South,LLC
state: South Carolina
city: Moncks Corner
country: United States
facility: Berkeley Family Practice
state: South Carolina
city: Bristol
country: United States
facility: Internal Medicine and Pediatric Associates of Bristol, PC
state: Tennessee
city: Corpus Christi
country: United States
facility: 3 rd Coast Research Associates
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development, Inc.
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Hurst
country: United States
facility: Protenium Clinical Research
state: Texas
city: Layton
country: United States
facility: Utah Cardiology, P.C.
state: Utah
city: Norfolk
country: United States
facility: National Clinical Research - Norfolk, Inc.
state: Virginia
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Milton
country: Australia
facility: Core Research Group Pty Ltd
state: Queensland
city: St. Kilda East
country: Australia
facility: The Avenue Cardiovascular Centre
state: Victoria
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Diex Research Montreal Inc.
state: Quebec
city: Quebec City
country: Canada
facility: ALPHA Recherche Clinique
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke (CHUS)
state: Quebec
city: Victoriaville
country: Canada
facility: Medexa Recherche
state: Quebec
city: Hradec Kralove
country: Czech Republic
facility: Fakultni nemocnice Hradec Kralove
city: Praha 5
country: Czech Republic
facility: Kardiologie a interni lekarstvi
city: Zlin
country: Czech Republic
facility: Lekarsky dum Ormiga
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Mitte GmbH
city: Hannover
country: Germany
facility: Klinische Forschung Hannover - Mitte GmbH
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH
city: Shatin, NT
country: Hong Kong
facility: Department of Medicine & Therapeutics-The Chinese University of Hong Kong
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: MI
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Fondazione Monzino
state: MI
city: Milano
country: Italy
facility: IRCCS Istituto Auxologico Italiano
state: MI
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"
state: PA
city: Roma
country: Italy
facility: Dipartimento di Medicina Interna e Specialita Mediche Policlinico Umberto I
state: RM
city: Uijeongbu-si
country: Korea, Republic of
facility: The Catholic University of Korea, Uijeongbu St. Mary's Hospital
state: Gyeonggi-do
city: Gangwon-Do
country: Korea, Republic of
facility: Yonsei University Wonju Severance Christian Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Gangnam Sevrance Hospital, Yeonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Katowice
country: Poland
facility: SYNEXUS Polska Sp. z o.o. Oddzial w Katowicach
state: Mazowieckie
city: Katowice
country: Poland
facility: NZOZ Terapia Optima
state: Slaskie
city: Gdynia
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdyni
city: Lodz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej CEREO-MED Sp. z o.o.
city: Opole
country: Poland
facility: Medicus w Opolu Sp z o.o.
city: Oswiecim
country: Poland
facility: Medicome Sp. z o.o.
city: Poznan
country: Poland
facility: Synexus Polska Sp. z o.o Oddzial w Poznaniu
city: Skierniewice
country: Poland
facility: Centrum Medyczne Ogrodowa Sp. z o.o.
city: Sopot
country: Poland
facility: Centrum Medyczne "SOPMED" Sp. z o.o.
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Warszawie
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Warszawa
country: Poland
facility: CSK MSW w Warszawie, Klinika Kardiologii Zachowawczej i Nadcisnienia Tetniczego
city: Wroclaw
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
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.