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

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ClinicalTrials.gov Identifier: NCT01994889
Recruitment Status : Completed
First Posted : November 26, 2013
Last Update Posted : May 7, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

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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


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




Primary Outcome Measures :
  1. All-cause mortality and frequency of cardiovascular-related hospitalization [ Time Frame: From Baseline to Month 30 ]
    A hierarchical combination of the endpoints for a pooled analysis of the tafamidis treatment groups in comparison to placebo


Secondary Outcome Measures :
  1. 6-Minute Walk Test (6MWT). [ Time Frame: From Baseline to Month 30 ]
    Change from Baseline to Month 30 in the total distance walked in 6 minutes.

  2. Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: From Baseline to Month 30 ]
    Change from Baseline to Month 30 in the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS).

  3. Cardiovascular-related mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths adjudicated as being related to cardiovascular causes.

  4. Frequency of cardiovascular-related hospitalization [ Time Frame: From Baseline to Month 30 ]
    The number of times that a subject is hospitalized for cardiovascular-related causes.

  5. All-cause mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths in the study.

  6. TTR stabilization at Month 1 [ Time Frame: From Baseline to Month 1 ]
    Tafamidis stabilizes the transthyretin (TTR) tetramer by binding with very high affinity to the two thyroxine binding sites, preventing the tetramer from dissociating along the weak dimer-dimer interface. TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis, expressed as a percentage change from baseline.



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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.

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


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

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     History of Changes
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
Last Update Posted: May 7, 2018
Last Verified: May 2018

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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
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases