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Completed

NCT Number: NCT01994889

Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy

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.

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Key information

Conditions

Transthyretin (TTR) Amyloid Cardiomyopathy Alzheimer Disease Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis Amyloidosis, Familial Brain Diseases Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dementia Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Mental Disorders Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Peripheral Nervous System Diseases Proteostasis Deficiencies Tauopathies

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Universitaire Ziekenhuizen Leuven, Leuven, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Tafamidis

Drug

Tafamidis 20 mg in soft gel capsules administered once a day for 30 months

Placebo

Drug

Placebo in soft gel capsules administered once a day for 30 months

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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)

Acronym: ATTR-ACT

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
Nov 26, 2013
Registry last updated
Apr 24, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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