Transthyretin (TTR) Amyloid CardiomyopathyPhase 3NCT02791230
Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy
A Phase 3 study testing Tafamidis in people with Transthyretin (TTR) Amyloid Cardiomyopathy, run by Pfizer at 80 sites in 17 countries.
Trial summary
Open label study to evaluate tafamidis for the treatment of transthyretin cardiomyopathy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transthyretin (TTR) Amyloid Cardiomyopathy
- What is being tested?
- Tafamidis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,733 participants
- Where
- 80 sitesin 17 countries
- Study dates
- 13 Jun 2016to 2 Nov 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- -Liver and/or heart transplant, or implanted cardiac mechanical assist device
Trial locations and contacts
80 sites in 17 countries.
80 sites in 17 countries
United States41 sites
Michigan Medicine,University of Michigan
Ann Arbor, Michigan, 48109
University of Maryland, Baltimore
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
California Heart Center
Beverly Hills, California, 90211
Cedars-Sinai Medical Care Foundation
Beverly Hills, California, 90211
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35233
Cardiovascular Clinical Trials Unit (CCTU)
Birmingham, Alabama, 35294
University Hospital, University of Alabama at Birmingham
Birmingham, Alabama, 35294
Boston Medical Center Investigational Pharmacy
Boston, Massachusetts, 02118
Boston Medical Center
Boston, Massachusetts, 02118
Boston University Medical Center
Boston, Massachusetts, 02118
Northwestern Medical Group
Chicago, Illinois, 60611
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
Sylvester at Deerfield Beach
Deerfield Beach, Florida, 33136
Duke University
Durham, North Carolina, 27710
Altman Clinical Translational Research Institute
La Jolla, California, 92037
University of California, San Diego
La Jolla, California, 92037
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Vanderbilt Univ. Med. Ctr
Nashville, Tennessee, 37232
NYU Langone Health
New York, New York, 10016
Center for Advanced Cardiac Care
New York, New York, 10032
Columbia University Irving Medical Center
New York, New York, 10032
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
OHSU Center for Health and Healing
Portland, Oregon, 97239
OHSU Research Pharmacy Services
Portland, Oregon, 97239
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic Hospital-Rochester
Rochester, Minnesota, 55902
Mayo Clinic
Rochester, Minnesota, 55905
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112
University of Utah Hospitals & Clinics
Salt Lake City, Utah, 84132
University of Utah, Division of Cardiovascular Medicine
Salt Lake City, Utah, 84132
University of California, San Diego Medical Center - Hillcrest
San Diego, California, 92103
Center Adv Lab Medicine
San Diego, California, 92121
UCSF Ambulatory Care Center
San Francisco, California, 94143
University of California
San Francisco, California, 94143
UCSF Cardiovascular Care and Prevention Center
San Francisco, California, 94158
Stanford University Hospital and Clinics
Stanford, California, 94305
France7 sites
CHU Henri Mondor
Créteil, 94010
Hopital de La Timone
Marseille, CAN, 13005
Hôpital De La Timone
Marseille, 13385
Hopital Bichat
Paris, 75018
CHU de Rennes - Hopital Pontchaillou
Rennes, 35033
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31059
Canada4 sites
University of Calgary/Foothills Medical Centre
Calgary, Alberta, T2N 4Z6
Montreal Heart Institute
Montreal, Quebec, H1T 1C8
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Australia3 sites
Eastern Health (Box Hill Hospital)
Box Hill, Victoria, 3128
Westmead Hospital
Westmead, New South Wales, 2145
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Czechia3 sites
Fakultni nemocnice u sv. Anny v Brne
Brno, 656 91
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Institut klinicke a experimentalni mediciny
Prague, 140 21
Italy3 sites
Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi
Bologna, 40138
Azienda Ospedaliero-Universitaria Careggi
Florence, 50134
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Japan3 sites
Kumamoto University Hospital
Kumamoto, Kumamoto, 860-8556
Kurume University Hospital
Kurume-shi, Fukuoka, 830-0011
Shinshu University Hospital
Nagano, 390-8621
Taiwan3 sites
Investigational Drug Services
Taipei, 100
National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 112
Germany2 sites
Medical University of Heidelberg
Heidelberg, 69120
Universitätsklinikum Münster
Münster, 48149
Hong Kong2 sites
Clinical Trial Pharmacy
Hong Kong
Queen Mary Hospital
Hong Kong
Spain2 sites
Unidad de Insuficiencia Cardiaca Avanzada y Transplante Cardiaco
A Coruña, LA Coruna, 15006
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Sweden2 sites
Skellefteå Lasarett
Skellefteå, 931 86
Akademiska Sjukhuset
Uppsala, 751 85
Argentina1 site
Instituto Cardiovascular de Buenos Aires
Buenos Aires, C1428ART
Brazil1 site
Hospital Universitário Clementino Fraga Filho (UFRJ)
Rio de Janeiro, Rio de Janeiro, 21941-913
United Kingdom1 site
Barts Health NHS Trust, St Bartholomew's Hospital
London, EC1A 7BE
About this study
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)
Open label study to evaluate tafamidis for the treatment of transthyretin cardiomyopathy
Read the 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.
- Being tested
- Tafamidis
- Keywords
- amyloidosis, amyloid, transthyretin, TTR, ATTR-CM
- Medical subject headings
- Amyloid Neuropathies, Familial, Amyloidosis, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TafamidisDrug
Soft gel capsules administered once a day for 60 months
| Study group | Role | What they receive |
|---|---|---|
| Tafamidis | Experimental | Active treatment - 61 mg or if not available, tafamidis meglumine 80 mg Receives: Drug: Tafamidis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study start13 Jun 2016
- Primary completion26 Oct 2023
- Study completion2 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Transthyretin (TTR) Amyloid CardiomyopathyStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,733 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02791230
- Sponsor's protocol ID
- B3461045
- Other IDs
- 2016-000868-42, 2016
- Status last verified
- Jan 2025
- First submitted
- 1 Jun 2016
- Last updated
- 3 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Fumagalli C, Cappelli F, Maurer MS, Aus dem Siepen F, Dispenzieri A, Garcia-Pavia P, Hanna M, Carlsson M, Damy T. Phenotypic Considerations for Tafamidis Use in a Real-World Cohort of Older Patients with Transthyretin Amyloid Cardiomyopathy. Cardiol Ther. 2026 Sep 11. doi: 10.1007/s40119-026-00474-4. Online ahead of print.
PubMed 42728504Fontana M, Aimo A, Grogan M, Crespo-Leiro MG, Maurer MS, Siepen FAD, Hanna M, Delgado D, Carlsson M, Damy T, Davis MK. Sex Differences in a Contemporary, Real-World Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis. Cardiol Ther. 2026 Sep 4. doi: 10.1007/s40119-026-00475-3. Online ahead of print.
PubMed 42693367Damy T, Witteles R, Cappelli F, Wang R, Grogan M. Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension. Cardiol Ther. 2026 Aug 27. doi: 10.1007/s40119-026-00470-8. Online ahead of print.
PubMed 42658466Aus dem Siepen F, Dispenzieri A, Hanna M, Carlsson M, Garcia-Pavia P. Survival in a Contemporary, Real-World, Matched Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated vs Not Treated with Tafamidis. Cardiol Ther. 2026 Aug 27. doi: 10.1007/s40119-026-00464-6. Online ahead of print.
PubMed 42658465Crespo-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.
PubMed 40934814Damy 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 Dec;27(12):2998-3009. doi: 10.1002/ejhf.3696. Epub 2025 Jun 9.
PubMed 40488446Drachman 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.
PubMed 38932583Garcia-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.
PubMed 37943223Elliott 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.
PubMed 37434378Elliott 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.
PubMed 36715498Elliott 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.
PubMed 34923848Damy 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.
PubMed 33070419Li 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.
PubMed 32524297