Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy
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)
2 other identifiers
interventional
1,733
17 countries
80
Brief Summary
Open label study to evaluate tafamidis for the treatment of transthyretin cardiomyopathy
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2016
Longer than P75 for phase_3
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 1, 2016
CompletedFirst Posted
Study publicly available on registry
June 6, 2016
CompletedStudy Start
First participant enrolled
June 13, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 26, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 2, 2023
CompletedResults Posted
Study results publicly available
February 3, 2025
CompletedFebruary 3, 2025
January 1, 2025
7.4 years
June 1, 2016
October 22, 2024
January 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Time to All-Cause Mortality: Cohort A
Time to all-cause mortality was calculated from first dose of randomized treatment in parent study (B3461028) to all-cause mortality events. All-cause mortality events included deaths, heart transplants and cardiac mechanical assist devices implantation treated as death. Treated participants from the parent study who discontinued prior to the start of this study were also included in this analysis as planned. Data from participants who dropped out for a liver-only transplantation were handled in the same manner as the data from all other censored participants. Censored participants were participants who completed study or discontinued from the study (including discontinued by sponsor or participants withdrew, or discontinued due to Adverse event (AE), or alive at the time of analysis. Kaplan Meier method was used for analysis. Therefore, this analysis was based on the pooled dose groups, as per the statistical analysis plan (SAP).
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]
Number of Participants With All-Cause Mortality Events: Cohort B
All-cause mortality included all participants who had discontinue for transplantation (i.e. heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death. Data from participants who dropped out for a liver-only transplantation were handled in the same manner as the data from all other censored participants. Censored participants were participants who completed study or discontinued from the study (including discontinued by sponsor or participants withdrew, or discontinued due to AE), or alive at the time of analysis. Kaplan Meier method was used for analysis.
B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
Number of Participants With Treatment-Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received investigational product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs included both SAEs and all Non-SAEs. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; considered an important medical event.
B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
Other Outcomes (15)
Time to Cardiovascular-Related Mortality Events: Cohort A
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]
Number of Participants With Cardiovascular Related Mortality Events: Cohort B
B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
Mean Annualized Rate of All Cause Hospitalizations
B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
- +12 more other outcomes
Study Arms (1)
Tafamidis
EXPERIMENTALActive treatment - 61 mg or if not available, tafamidis meglumine 80 mg
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Liver and/or heart transplant, or implanted cardiac mechanical assist device
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (80)
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35233, United States
Cardiovascular Clinical Trials Unit (CCTU)
Birmingham, Alabama, 35294, United States
University Hospital, University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
California Heart Center
Beverly Hills, California, 90211, United States
Cedars-Sinai Medical Care Foundation
Beverly Hills, California, 90211, United States
Altman Clinical Translational Research Institute
La Jolla, California, 92037, United States
University of California, San Diego
La Jolla, California, 92037, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California, San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
Center Adv Lab Medicine
San Diego, California, 92121, United States
UCSF Ambulatory Care Center
San Francisco, California, 94143, United States
University of California
San Francisco, California, 94143, United States
UCSF Cardiovascular Care and Prevention Center
San Francisco, California, 94158, United States
Stanford University Hospital and Clinics
Stanford, California, 94305, United States
Sylvester at Deerfield Beach
Deerfield Beach, Florida, 33136, United States
University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Northwestern Medical Group
Chicago, Illinois, 60611, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453, United States
University of Maryland, Baltimore
Baltimore, Maryland, 21201, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Boston Medical Center Investigational Pharmacy
Boston, Massachusetts, 02118, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Boston University Medical Center
Boston, Massachusetts, 02118, United States
Michigan Medicine,University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic Hospital-Rochester
Rochester, Minnesota, 55902, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
NYU Langone Health
New York, New York, 10016, United States
Center for Advanced Cardiac Care
New York, New York, 10032, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
Duke University
Durham, North Carolina, 27710, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
OHSU Center for Health and Healing
Portland, Oregon, 97239, United States
OHSU Research Pharmacy Services
Portland, Oregon, 97239, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt Univ. Med. Ctr
Nashville, Tennessee, 37232, United States
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112, United States
University of Utah Hospitals & Clinics
Salt Lake City, Utah, 84132, United States
University of Utah, Division of Cardiovascular Medicine
Salt Lake City, Utah, 84132, United States
Instituto Cardiovascular de Buenos Aires
Buenos Aires, C1428ART, Argentina
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Eastern Health (Box Hill Hospital)
Box Hill, Victoria, 3128, Australia
UZ Leuven
Leuven, 3000, Belgium
Hospital Universitário Clementino Fraga Filho (UFRJ)
Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil
University of Calgary/Foothills Medical Centre
Calgary, Alberta, T2N 4Z6, Canada
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9, Canada
Toronto General Hospital
Toronto, Ontario, M5G 2C4, Canada
Montreal Heart Institute
Montreal, Quebec, H1T 1C8, Canada
Fakultni nemocnice u sv. Anny v Brne
Brno, 656 91, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 128 08, Czechia
Institut klinicke a experimentalni mediciny
Prague, 140 21, Czechia
Hopital de La Timone
Marseille, CAN, 13005, France
CHU Henri Mondor
Créteil, 94010, France
Hôpital De La Timone
Marseille, 13385, France
Hopital Bichat
Paris, 75018, France
CHU de Rennes - Hopital Pontchaillou
Rennes, 35033, France
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033, France
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31059, France
Medical University of Heidelberg
Heidelberg, 69120, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Clinical Trial Pharmacy
Hong Kong, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi
Bologna, 40138, Italy
Azienda Ospedaliero-Universitaria Careggi
Florence, 50134, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Kurume University Hospital
Kurume-shi, Fukuoka, 830-0011, Japan
Kumamoto University Hospital
Kumamoto, Kumamoto, 860-8556, Japan
Shinshu University Hospital
Nagano, 390-8621, Japan
University Medical Center Groningen
Groningen, 9713 GZ, Netherlands
Unidad de Insuficiencia Cardiaca Avanzada y Transplante Cardiaco
A Coruña, LA Coruna, 15006, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222, Spain
Skellefteå Lasarett
Skellefteå, 931 86, Sweden
Akademiska Sjukhuset
Uppsala, 751 85, Sweden
Investigational Drug Services
Taipei, 100, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Taipei Veterans General Hospital
Taipei, 112, Taiwan
Barts Health NHS Trust, St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
Related Publications (9)
Crespo-Leiro MG, Hanna M, Damy T, Delgado D, Ebede B, Marino V, Wang R, Maurer MS, Garcia-Pavia P, Drachman BM. Early Access to Tafamidis for Patients With Transthyretin Amyloid Cardiomyopathy. JACC Adv. 2025 Oct;4(10 Pt 2):102122. doi: 10.1016/j.jacadv.2025.102122. Epub 2025 Sep 10.
PMID: 40934814DERIVEDDamy T, Wang R, Maurer MS, Gillmore JD, Fontana M. Long-term efficacy of tafamidis in patients with transthyretin amyloid cardiomyopathy by National Amyloidosis Centre stage. Eur J Heart Fail. 2025 Jun 9. doi: 10.1002/ejhf.3696. Online ahead of print.
PMID: 40488446DERIVEDDrachman B, Damy T, Hanna M, Wang R, Angeli FS, Garcia-Pavia P. Long-term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction. Eur J Heart Fail. 2024 Sep;26(9):2038-2046. doi: 10.1002/ejhf.3330. Epub 2024 Jun 26.
PMID: 38932583DERIVEDGarcia-Pavia P, Sultan MB, Gundapaneni B, Sekijima Y, Perfetto F, Hanna M, Witteles R. Tafamidis Efficacy Among Octogenarian Patients in the Phase 3 ATTR-ACT and Ongoing Long-Term Extension Study. JACC Heart Fail. 2024 Jan;12(1):150-160. doi: 10.1016/j.jchf.2023.08.032. Epub 2023 Nov 8.
PMID: 37943223DERIVEDElliott P, Gundapaneni B, Sultan MB, Ines M, Garcia-Pavia P. Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms. Eur J Heart Fail. 2023 Nov;25(11):2060-2064. doi: 10.1002/ejhf.2974. Epub 2023 Jul 26.
PMID: 37434378DERIVEDElliott P, Drachman BM, Gottlieb SS, Hoffman JE, Hummel SL, Lenihan DJ, Ebede B, Gundapaneni B, Li B, Sultan MB, Shah SJ. Long-term survival in people with transthyretin amyloid cardiomyopathy who took tafamidis: A Plain Language Summary. Future Cardiol. 2023 Jan;19(1):7-17. doi: 10.2217/fca-2022-0096. Epub 2023 Jan 30.
PMID: 36715498DERIVEDElliott 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.
PMID: 34923848DERIVEDDamy 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.
PMID: 33070419DERIVEDLi 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.
PMID: 32524297DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
For analyses in current extension study for Cohort A based on CMA set, it combined data from participants in parent study B3461028, including participants who died, discontinued in parent study B3461028, or did not enroll into the current extension study B3461045.Data for these participants is used only in few planned outcomes and these participants do not reflect in any other section of this record. For reference, results for B3461028 can be found at ClinicalTrails.gov with NCT ID: NCT01994889.
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 1, 2016
First Posted
June 6, 2016
Study Start
June 13, 2016
Primary Completion
October 26, 2023
Study Completion
November 2, 2023
Last Updated
February 3, 2025
Results First Posted
February 3, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.