Clinical trial NCT01968980: A 52 Week Study To Assess The Use Of Bococizumab (PF-04950615; RN316) In Subjects With Heterozygous Familial Hypercholesterolemia
Official title: A 52 Week, Phase 3 Double-blind, Randomized, Placebo-controlled, Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heterozygous Familial Hypercholesterolemia
Keywords: High Risk of cardiovascular events
Heterozygous familial hypercholesterolemia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-10-24
Enrollment: 370
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 is a multicenter, randomized study in subjects with heterozygous familial hypercholesterolemia receiving highly effective statins to assess the safety, efficacy 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.
* Heterozygous familial hypercholesterolemia.

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
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Total Cholesterol (TC) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Lipoprotein (a) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and 52
timeFrame: Baseline, Week 24, 52
measure: Percent Change From Baseline in Triglycerides (TG) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percent Change From Baseline in Apolipoprotein A-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 Low Density Lipoprotein (LDL-C) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Total Cholesterol (TC) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Lipoprotein (a) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Ratio of 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 Apolipoprotein A-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52
timeFrame: Baseline, Week 12, 24, 52
measure: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than or Equal to (<=) 100 Milligram Per Deciliter (2.59 Millimoles Per Liter) at Week 12, 24 and 52
timeFrame: Week 12, 24, 52
measure: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than or Equal to (<=) 70 Milligram Per Deciliter (1.81 Millimoles Per Liter) at Week 12, 24 and 52
timeFrame: Week 12, 24, 52
measure: Plasma PF-04950615 Concentrations at Week 12, 24 and 52
timeFrame: Week 12, 24, 52
measure: Number of Participants With Adverse Events 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 Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
timeFrame: Baseline up to the end of study (up to 58 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: IMD Medical Group
state: California
city: Hartford
country: United States
facility: Hartford Hospital, JB704
state: Connecticut
city: Hialeah
country: United States
facility: Best Quality Research, Inc.
state: Florida
city: Miami Beach
country: United States
facility: NewPhase Clinical Trials, Corp.
state: Florida
city: Miami
country: United States
facility: Medical Research Center
state: Florida
city: Miami
country: United States
facility: Premier Research Associate, Inc
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services, LLC
state: Florida
city: Las Vegas
country: United States
facility: Om Medical
state: Nevada
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill Center for Heart & Vascular Care
state: North Carolina
city: Chapel Hill
country: United States
facility: The University of North Carolina Hospitals - Clinical and Translational Research Center Clinic
state: North Carolina
city: Cincinnati
country: United States
facility: Metabolic and Atherosclerosis Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital Physicians
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital Research Foundation
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Gaffney
country: United States
facility: OnSite Clinical Solutions, LLC
state: South Carolina
city: Dallas
country: United States
facility: Galenos Research
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Draper
country: United States
facility: Focus Clinical Research, LLC
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine & Research
state: Virginia
city: Pleven
country: Bulgaria
facility: SHAT in Cardiology EAD
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi" EAD, Clinic of Cardiology
city: Sofia
country: Bulgaria
facility: Second MHAT - Sofia EAD
city: Sofia
country: Bulgaria
facility: MHAT "Sveta Anna", Clinic of Internal Diseases
city: Vancouver
country: Canada
facility: St. Paul's Hospital, Healthy Heart
state: British Columbia
city: Victoria
country: Canada
facility: Discovery Clinical Services Ltd.
state: British Columbia
city: Winnipeg
country: Canada
facility: Asper Clinical Research Institute
state: Manitoba
city: St. John's
country: Canada
facility: Health Sciences Centre
state: Newfoundland and Labrador
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Institut de Recherches Cliniques de Montreal
state: Quebec
city: Quebec
country: Canada
facility: Clinique des maladies lipidiques de Quebec Inc
city: Helsinki
country: Finland
facility: Helsinki Central University Hospital
city: Joensuu
country: Finland
facility: Pohjois-Karjala Projekti Saatio/Ita-Suomen
city: Joensuu
country: Finland
facility: Pohjois-Karjala Projekti Saatio
city: Kerava
country: Finland
facility: Laakarikeskus Aava Kerava/Aava Kerava Medical Center
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Turku
country: Finland
facility: Division of Medicine Turku University Hospital
city: Palermo
country: Italy
facility: Policlinico "Paolo Giaccone"
state: PA
city: Perugia
country: Italy
facility: Ospedale "Santa Maria della Misericordia"
state: PG
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
state: VA
city: Napoli
country: Italy
facility: Azienda Ospedaliero Universitaria "Federico II" di Napoli
city: Goes
country: Netherlands
facility: Admiraal de Ruyter ziekenhuis
state: Zeeland
city: Rotterdam
country: Netherlands
facility: St. Franciscus Gasthuis
state: Zuid-holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Rotterdam Research Institute
city: Sliedrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ulleval
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Krakow
country: Poland
facility: NZOZ Centrum Zdrowia i Profilaktyki Dabie Sp zo.o.
city: Ruda Slaska
country: Poland
facility: NZOZ Przychodnia Specjalistyczna Andrzej Wittek Henryk Rudzki S.C
city: Bloemfontein
country: South Africa
facility: IATROS International
state: Free State
city: Centurion
country: South Africa
facility: Unitas hospital
state: Gauteng
city: Halfway House
country: South Africa
facility: Midrand Medical Centre
state: Gauteng
city: Pretoria
country: South Africa
facility: Medipark Centre for Clinical Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Jongaie Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Synexus Watermeyer Clinical Research Centre
state: Gauteng
city: Roodepoort
country: South Africa
facility: Roodepoort Medicross Clinical Research Centre
state: Gauteng
city: Durban
country: South Africa
facility: Chelmsford Medical Centre 3
state: Kwa-zulu Natal
city: Bellville, Cape Town
country: South Africa
facility: Tiervlei Trial Centre, Karl Bremer Hospital
state: Western Cape
city: Parow, Cape Town
country: South Africa
facility: TREAD Research cc.
state: Western Cape
city: Somerset West
country: South Africa
facility: Synexus Helderberg Clinical Research Centre
state: Western Cape
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario, Santiago de Compostela
state: Galicia
city: Reus
country: Spain
facility: Hospital Universitario Sant Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz; Servicio de Medicina Interna
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos; U. de Lipidos; Medicina Interna III
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Miguel Servet; Medicina Interna
city: Manchester
country: United Kingdom
facility: Clinical Trials Pharmacy, 4th Floor Inpatient Pharmacy
state: Greater Manchester
city: Oldham
country: United Kingdom
facility: Pennine Acute Hospitals NHS Trust
state: Greater Manchester
city: Stevenage
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Hertfordshire
city: Burton-on-Trent
country: United Kingdom
facility: Burton Hospitals NHS Foundation Trust
state: Staffordshire
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust
state: West Midlands
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust
city: Peterborough
country: United Kingdom
facility: Peterborough and Stamford Hospitals NHS Foundation Trust
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: 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.