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Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy (ATTR-ACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01994889
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : April 3, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:
This Phase 3 study will investigate the efficacy, safety and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to placebo in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.

Condition or disease Intervention/treatment Phase
Transthyretin (TTR) Amyloid Cardiomyopathy Drug: Tafamidis Drug: Placebo Phase 3

Detailed Description:
Phase 3, multicenter, global, three-arm, parallel design, placebo-controlled, double-blind, randomized study to determine efficacy, safety and tolerability of tafamidis on clinical outcomes (all-cause mortality and frequency of cardiovascular-related hospitalizations) in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 441 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A MULTICENTER, INTERNATIONAL, PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF DAILY ORAL DOSING OF TAFAMIDIS MEGLUMINE (PF-06291826) 20 MG OR 80 MG IN COMPARISON TO PLACEBO IN SUBJECTS DIAGNOSED WITH TRANSTHYRETIN CARDIOMYOPATHY (TTR-CM)
Actual Study Start Date : December 9, 2013
Actual Primary Completion Date : February 7, 2018
Actual Study Completion Date : February 7, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiomyopathy

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tafamidis - 20 mg
Active Treatment-Low dose
 Drug: Tafamidis
Tafamidis 20 mg in soft gel capsules administered once a day for 30 months
Experimental: Tafamidis - 80 mg
Active Treatment-High Dose
 Drug: Tafamidis
Tafamidis 80 mg in soft gel capsules administered once a day for 30 months
Placebo Comparator: Placebo
Placebo control
 Drug: Placebo
Placebo in soft gel capsules administered once a day for 30 months


Outcome Measures
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Primary Outcome Measures :
  1. Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations [ Time Frame: Baseline up to Month 30 ]
    All-cause mortality and frequency of cardiovascular hospitalization were analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality and frequency of CV-related hospitalizations in a hierarchical fashion using all-cause mortality first. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who discontinued for transplantation (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. 'Win' represents a participant doing better based on hierarchical comparison. The reported unit is the total "wins" for each treatment group from performing such a hierarchical comparison across all 4 strata in the study.


Secondary Outcome Measures :
  1. All-Cause Mortality [ Time Frame: Baseline up to Month 30 ]
    Number of deaths due to any cause was analyzed. Participants who discontinued for transplantation (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.

  2. Frequency of Cardiovascular-Related Hospitalizations [ Time Frame: Baseline to Month 30 ]
    CV related hospitalizations per year is calculated as participant's number of CV related hospitalizations upon duration on study in years.

  3. Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30 [ Time Frame: Baseline, Month 30 ]
    6MWT is the total distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

  4. Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30 [ Time Frame: Baseline, Month 30 ]
    KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). Two summary scores were also calculated: Clinical Summary (calculated as mean of Physical limitation and Total symptom scores) and Overall Summary (calculated as mean of Physical limitation, Social limitation, Total symptoms, and Quality of life scores). Domain and summary scores were scaled to range from 0 (minimum) to 100 (maximum); higher scores represent better health status.

  5. Number of Participants With Cardiovascular-Related Mortality [ Time Frame: Baseline up to Month 30 ]
    Deaths adjudicated as CV-related and indeterminate are reported. Participants who discontinued for transplantation (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.

  6. Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1 [ Time Frame: Month 1 ]
    TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement,
  • Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm,
  • Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry

Exclusion Criteria:

  • A New York Heart Association (NYHA) classification of IV.
  • Presence of primary (light chain) amyloidosis.
  • Prior liver or heart transplantation or implanted cardiac mechanical assist device.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994889


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] May 24, 2016
Statistical Analysis Plan  [PDF] January 30, 2018

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01994889    
Other Study ID Numbers: B3461028
2012-002465-35 ( EudraCT Number )
ATTR-ACT ( Other Identifier: Alias Study Number )
First Posted: November 26, 2013    Key Record Dates
Results First Posted: April 3, 2019
Last Update Posted: April 24, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
amyloidosis
amyloid
transthyretin
TTR
Additional relevant MeSH terms:
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Cardiomyopathies
Heart Diseases
Cardiovascular Diseases