Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy

Study at a glance

From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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)

ClinicalTrials.gov ID

NCT02791230

Acronym / sponsor ID

B3461045

Conditions

Transthyretin (TTR) Amyloid Cardiomyopathy

Keywords

amyloidosis, amyloid, transthyretin, TTR, ATTR-CM

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

1,733 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

13 Jun 2016 (actual)

Primary completion

26 Oct 2023 (actual)

Study completion

2 Nov 2023 (actual)

First posted

6 Jun 2016 (estimated)

Results

Posted 3 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Not applicable

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

1

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Time to All-Cause Mortality: Cohort A

   Time frame: 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]

   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).

2. Number of Participants With All-Cause Mortality Events: Cohort B

   Time frame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)

   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.

3. Number of Participants With Treatment-Emergent Adverse Events (AEs)

   Time frame: B3461045: From first dose of treatment up to 28 days post last dose of study treatment (approximately up to 61 months)

   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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 42728504Fumagalli 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.
• Derived from this study: PubMed 42693367Fontana 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.
• Derived from this study: PubMed 42658466Damy 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.
• Derived from this study: PubMed 42658465Aus 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.
• Derived from this study: PubMed 40934814Crespo-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.
• Derived from this study: PubMed 40488446Damy 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.
• Derived from this study: PubMed 38932583Drachman 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.
• Derived from this study: PubMed 37943223Garcia-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.
• Derived from this study: PubMed 37434378Elliott 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.
• Derived from this study: 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 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.
• Derived from this study: PubMed 34923848Elliott 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.
• Derived from this study: PubMed 33070419Damy 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.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

80 sites in 17 countries: see every site and its status.