Clinical trial NCT02791230: Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy
Official title: A PHASE 3 MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY OF DAILY ORAL DOSING OF TAFAMIDIS MEGLUMINE (PF-06291826-83) 20 MG OR 80 MG [OR TAFAMIDIS (PF-06291826-00) 61 MG] IN SUBJECTS DIAGNOSED WITH TRANSTHYRETIN CARDIOMYOPATHY (ATTR-CM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Transthyretin (TTR) Amyloid Cardiomyopathy
Keywords: amyloidosis
amyloid
transthyretin
TTR
ATTR-CM
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-06-06
Enrollment: 1733
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Open label study to evaluate tafamidis for the treatment of transthyretin cardiomyopathy

Detailed description: Global Phase 3, open label long term extension safety study designed to obtain additional safety data for tafamidis meglumine 20 mg and 80 mg (or tafamidis 61 mg where available), and to continue to provide enrolled subjects with tafamidis for up to 60 months, or until subject has access to tafamidis for ATTR CM via prescription, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

Cohort A: Completion of 30 months of study treatment on Pfizer Protocol B3461028

Cohort B: Patients in specific countries diagnosed with ATTR-CM who did not previously participate in Pfizer Study B3461028

Exclusion Criteria:

-Liver and/or heart transplant, or implanted cardiac mechanical assist device

Primary outcomes:
measure: Time to All-Cause Mortality: Cohort A
timeFrame: From first dose of randomized treatment in parent study (B3461028) up to 28 days post last dose of study treatment in current extension study (B3461045), [approximately up to 91 months]
measure: Number of Participants With All-Cause Mortality Events: Cohort B
timeFrame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
Secondary outcomes:
Other outcomes:
measure: Time to Cardiovascular-Related Mortality Events: Cohort A
timeFrame: From first dose of randomized treatment in parent study (B3461028) up to 28 days post last dose of study treatment in current extension study (B3461045), [approximately up to 91 months]
measure: Number of Participants With Cardiovascular Related Mortality Events: Cohort B
timeFrame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
measure: Mean Annualized Rate of All Cause Hospitalizations
timeFrame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
measure: Mean Annualized Rate of Cardiovascular (CV)-Related Hospitalizations
timeFrame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Scores at Months 12, 30, 42, 60 and 90: Cohort A
timeFrame: B3461028: Baseline (Day 1, pre-dose), Months 12, 30; B3461045: Months 42, 60 and 90 (time points were relative to Day 1 from B3461028; 42, 60 and 90 Months were 12, 30 and 60 Months of B3461045)
measure: Change From Baseline in KCCQ Overall Score at Months 12, 30, 42, 60, 90: Cohort A
timeFrame: B3461028: Baseline (Day 1, pre-dose), Months 12, 30; B3461045: Months 42, 60 and 90 (time points were relative to Day 1 from B3461028; 42, 60 and 90 Months were 12, 30 and 60 Months of B3461045)
measure: Change From Baseline in KCCQ Total Symptom Score at Months 12, 30, 42, 60 and 90: Cohort A
timeFrame: B3461028: Baseline (Day 1, pre-dose), Months 12, 30; B3461045: Months 42, 60 and 90 (time points were relative to Day 1 from B3461028; 42, 60 and 90 Months were 12, 30 and 60 Months of B3461045)
measure: Change From Baseline in KCCQ Clinical Summary Scores at Months 12, 30 and 54: Cohort B
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 12, 30 and 54
measure: Change From Baseline in KCCQ Overall Score at Months 12, 30 and 54: Cohort B
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 12, 30 and 54
measure: Change From Baseline in KCCQ Total Symptom Score at Months 12, 30 and 54: Cohort B
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 12, 30 and 54
measure: Number of Participants With Shift From Baseline in New York Heart Association (NYHA) Classification at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
measure: Change From Baseline in Body Mass Index (BMI) at Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
measure: Change From Baseline in Modified Body Mass Index (mBMI) at Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
measure: Change From Baseline in Troponin I Concentration at Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: B3461045: Baseline (Day 1, pre-dose), Months 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic of UAB Hospital
state: Alabama
city: Birmingham
country: United States
facility: Cardiovascular Clinical Trials Unit (CCTU)
state: Alabama
city: Birmingham
country: United States
facility: University Hospital, University of Alabama at Birmingham
state: Alabama
city: Beverly Hills
country: United States
facility: California Heart Center
state: California
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Care Foundation
state: California
city: La Jolla
country: United States
facility: Altman Clinical Translational Research Institute
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego Medical Center - Hillcrest
state: California
city: San Diego
country: United States
facility: Center Adv Lab Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Ambulatory Care Center
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: San Francisco
country: United States
facility: UCSF Cardiovascular Care and Prevention Center
state: California
city: Stanford
country: United States
facility: Stanford University Hospital and Clinics
state: California
city: Deerfield Beach
country: United States
facility: Sylvester at Deerfield Beach
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Group
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center Investigational Pharmacy
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine,University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Hospital-Rochester
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Center for Advanced Cardiac Care
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: OHSU Center for Health and Healing
state: Oregon
city: Portland
country: United States
facility: OHSU Research Pharmacy Services
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Univ. Med. Ctr
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospitals & Clinics
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah, Division of Cardiovascular Medicine
state: Utah
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Instituto Cardiovascular de Buenos Aires
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health (Box Hill Hospital)
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitário Clementino Fraga Filho (UFRJ)
state: RJ
city: Calgary
country: Canada
facility: University of Calgary/Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 4
country: Czechia
facility: Institut klinicke a experimentalni mediciny
city: Marseille
country: France
facility: Hopital de La Timone
state: CAN
city: Creteil
country: France
facility: CHU Henri Mondor
city: Marseille
country: France
facility: Hôpital De La Timone
city: Paris
country: France
facility: Hopital Bichat
city: Rennes
country: France
facility: CHU de Rennes - Hopital Pontchaillou
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Rangueil
city: Heidelberg
country: Germany
facility: Medical University of Heidelberg
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Hong Kong
country: Hong Kong
facility: Clinical Trial Pharmacy
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Kumamoto-city
country: Japan
facility: Kumamoto University Hospital
state: Kumamoto
city: Nagano
country: Japan
facility: Shinshu University Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: A Coruna
country: Spain
facility: Unidad de Insuficiencia Cardiaca Avanzada y Transplante Cardiaco
state: LA Coruna
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Skellefteå
country: Sweden
facility: Skellefteå Lasarett
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Taipei
country: Taiwan
facility: Investigational Drug Services
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust, St Bartholomew's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Elliott P, Drachman BM, Gottlieb SS, Hoffman JE, Hummel SL, Lenihan DJ, Ebede B, Gundapaneni B, Li B, Sultan MB, Shah SJ. Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy. Circ Heart Fail. 2022 Jan;15(1):e008193. doi: 10.1161/CIRCHEARTFAILURE.120.008193. Epub 2021 Dec 20.
citation: Damy T, Garcia-Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B, Patterson TA, Riley S, Schwartz JH, Sultan MB, Witteles R. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021 Feb;23(2):277-285. doi: 10.1002/ejhf.2027. Epub 2020 Nov 12.
citation: Li B, Alvir J, Stewart M. Extrapolation of Survival Benefits in Patients with Transthyretin Amyloid Cardiomyopathy Receiving Tafamidis: Analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. Cardiol Ther. 2020 Dec;9(2):535-540. doi: 10.1007/s40119-020-00179-2. Epub 2020 Jun 10.