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

April 15, 2019 updated by: Pfizer

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

441

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Universitaire Ziekenhuizen Leuven
  • Brazil
    • RJ
      • Rio de Janeiro, RJ, Brazil, 21941-913
        • Unidade de Pesquisa Clinica / Hospital Universitario Clementino Fraga Filho / UFRJ
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary/Foothills Medical Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • Toronto General Hospital
  • Czechia
      • Brno, Czechia, 656 91
        • Fakultni nemocnice u sv. Anny, Nemocnicni lekarna
      • Brno, Czechia, 656 91
        • Nemocnice u sv. Anny v Brne
      • Praha 2, Czechia, 128 08
        • Vseobecna fakultni nemocnice v Praze
      • Praha 2, Czechia, 12808
        • Vseobecna fakultni nemocnice v Praze, Nemocnicni lekarna
      • Praha 4, Czechia, 140 21
        • IKEM, Ustavni lekarna
      • Praha 4, Czechia, 140 21
        • IKEM
  • France
      • Clamart, France, 92140
        • Hôpital Antoine Béclère
      • Creteil, France, 94010
        • CHU Henri Mondor
  • Germany
      • Heidelberg, Germany, 69120
        • Medical University of Heidelberg
      • Muenster, Germany, 48149
        • Universitaetsklinikum Muenster
  • Italy
      • Bologna, Italy, 40138
        • U.O. Cardiologia- Prof. Rapezzi
      • Brescia, Italy, 25123
        • Unita Operativa di Cardiologia
      • Firenze, Italy, 50134
        • S.O.D. Cardiologia Generale 1 - D.A.I. del Cuore e dei Vasi
      • Pavia, Italy, 27100
        • Centro per lo Studio e la Cura Delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S. Matteo
  • Japan
      • Nagano, Japan, 390-8621
        • Shinshu University Hospital
    • Fukuoka
      • Kurume-shi, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Kumamoto
      • Kumamoto-city, Kumamoto, Japan, 8608556
        • Kumamoto University Hospital
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
  • Spain
      • A Coruna, Spain, 15006
        • Hospital Universitario A Coruña
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro - Majadahonda
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Clínico Universitario Virgen de la Arrixaca
  • Sweden
      • Skelleftea, Sweden, 93186
        • Medicin-Geriatrik kliniken-Skelleftea lasarett
      • Uppsala, Sweden, 751 85
        • Sjukhusvägen, Akademiska sjukhuset
  • United Kingdom
      • London, United Kingdom, SW17 0RE
        • St. George's University of London
      • London, United Kingdom, EC1A 7BE
        • St Bartholomew's Hospital-Barts Health NHS Trust
      • London, United Kingdom, SW17 0QT
        • St. George's Hospital (St George's Healthcare NHS Trust)
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • The Kirklin Clinic
      • Birmingham, Alabama, United States, 35249
        • UAB Hospital Department of Pharmacy IDS
      • Birmingham, Alabama, United States, 35249
        • University Hospital, University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Arizona - Mayo Clinic Speciality Building
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Arizona - Mayo Clinic Building
    • California
      • La Jolla, California, United States, 92037
        • Altman Clinical Translational Research Institute
      • La Jolla, California, United States, 92037
        • UCSD Sulpizio Cardiovascular Center
      • La Jolla, California, United States, 92037-0620
        • UCSD Clinical and Translational Research Institute, Investigational Drug Service
      • La Jolla, California, United States, 92037-0990
        • Altman Clinical Translational Research Institute
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center, Investigational Drug Pharmacy Services
      • Los Angeles, California, United States, 90211
        • Cedars-Sinai Medical Care Foundation
      • San Francisco, California, United States, 94143
        • UCSF Cardiovascular Care and Prevention Center
      • Stanford, California, United States, 94305
        • Stanford University Hospital and Clinics
    • Florida
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester at Deerfield Beach
      • Miami, Florida, United States, 33136
        • University of Miami Hospital & Clinics
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60611
        • Northwestern Medical Group
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Christ Medical Centre
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, School of Medicine
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital IDS Pharmacy
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center - Cardiovascular Center, Outpatient Clinic
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center Investigational Pharmacy Services
      • Boston, Massachusetts, United States, 02118
        • Boston University Medical Center General Clinical Research Unit
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Michigan Medicine,University of Michigan
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Pharmacy Research Supp
    • New Jersey
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital
      • New York, New York, United States, 10016
        • New York University Hospitals
      • New York, New York, United States, 10029
        • Mount Sinai Doctors Faculty Practice
      • New York, New York, United States, 10029
        • The Mount Sinai Hospital Department of Pharmacy
      • New York, New York, United States, 10032
        • Columbia University Medical Center Research Pharmacy
      • New York, New York, United States, 10034
        • Columbia University Medical Center/Clinical Cardiovascular Research Laboratory for the Elderly
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Center for Health and Healing
      • Portland, Oregon, United States, 97239
        • OHSU Research Pharmacy Services
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University (OHSU)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Presbyterian Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah,Health Sciences Center
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Medical Center - Ambulatory Care Clinic
      • Richmond, Virginia, United States, 23298
        • VCU Medical Center - Main Hospital
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 88 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline up to Month 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline up to Month 30
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.
Baseline to Month 30
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.
Baseline, Month 30
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.
Baseline, Month 30
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.
Baseline up to Month 30
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.
Month 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 9, 2013

Primary Completion (Actual)

February 7, 2018

Study Completion (Actual)

February 7, 2018

Study Registration Dates

First Submitted

November 14, 2013

First Submitted That Met QC Criteria

November 20, 2013

First Posted (Estimate)

November 26, 2013

Study Record Updates

Last Update Posted (Actual)

April 24, 2019

Last Update Submitted That Met QC Criteria

April 15, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B3461028
  • 2012-002465-35 (EudraCT Number)
  • ATTR-ACT (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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