Transthyretin (TTR) Amyloid Cardiomyopathy Clinical Trial
— ATTR-ACTOfficial 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)
| Verified date | April 2019 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 441 |
| Est. completion date | February 7, 2018 |
| Est. primary completion date | February 7, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 90 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Universitaire Ziekenhuizen Leuven | Leuven | |
| Brazil | Unidade de Pesquisa Clinica / Hospital Universitario Clementino Fraga Filho / UFRJ | Rio de Janeiro | RJ |
| Canada | University of Calgary/Foothills Medical Centre | Calgary | Alberta |
| Canada | Toronto General Hospital | Toronto | Ontario |
| Czechia | Fakultni nemocnice u sv. Anny, Nemocnicni lekarna | Brno | |
| Czechia | Nemocnice u sv. Anny v Brne | Brno | |
| Czechia | Vseobecna fakultni nemocnice v Praze | Praha 2 | |
| Czechia | Vseobecna fakultni nemocnice v Praze, Nemocnicni lekarna | Praha 2 | |
| Czechia | IKEM | Praha 4 | |
| Czechia | IKEM, Ustavni lekarna | Praha 4 | |
| France | Hopital Antoine Beclere | Clamart | |
| France | CHU Henri Mondor | Creteil | |
| Germany | Medical University of Heidelberg | Heidelberg | |
| Germany | Universitaetsklinikum Muenster | Muenster | |
| Italy | U.O. Cardiologia- Prof. Rapezzi | Bologna | |
| Italy | Unita Operativa di Cardiologia | Brescia | |
| Italy | S.O.D. Cardiologia Generale 1 - D.A.I. del Cuore e dei Vasi | Firenze | |
| Italy | Centro per lo Studio e la Cura Delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S. Matteo | Pavia | |
| Japan | Kumamoto University Hospital | Kumamoto-city | Kumamoto |
| Japan | Kurume University Hospital | Kurume-shi | Fukuoka |
| Japan | Shinshu University Hospital | Nagano | |
| Netherlands | University Medical Center Groningen | Groningen | |
| Spain | Hospital Universitario A Coruna | A Coruna | |
| Spain | Hospital Clinico Universitario Virgen de la Arrixaca | El Palmar | Murcia |
| Spain | Hospital Universitario Puerta De Hierro - Majadahonda | Majadahonda | Madrid |
| Sweden | Medicin-Geriatrik kliniken-Skelleftea lasarett | Skelleftea | |
| Sweden | Sjukhusvägen, Akademiska sjukhuset | Uppsala | |
| United Kingdom | St Bartholomew's Hospital-Barts Health NHS Trust | London | |
| United Kingdom | St. George's Hospital (St George's Healthcare NHS Trust) | London | |
| United Kingdom | St. George's University of London | London | |
| United States | Michigan Medicine,University of Michigan | Ann Arbor | Michigan |
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | The Johns Hopkins Hospital IDS Pharmacy | Baltimore | Maryland |
| United States | University of Maryland, School of Medicine | Baltimore | Maryland |
| United States | The Kirklin Clinic | Birmingham | Alabama |
| United States | UAB Hospital Department of Pharmacy IDS | Birmingham | Alabama |
| United States | University Hospital, University of Alabama at Birmingham | Birmingham | Alabama |
| United States | Boston Medical Center | Boston | Massachusetts |
| United States | Boston Medical Center - Cardiovascular Center, Outpatient Clinic | Boston | Massachusetts |
| United States | Boston Medical Center Investigational Pharmacy Services | Boston | Massachusetts |
| United States | Boston University Medical Center General Clinical Research Unit | Boston | Massachusetts |
| United States | Northwestern Medical Group | Chicago | Illinois |
| United States | Northwestern Memorial Hospital | Chicago | Illinois |
| United States | Cleveland Clinic | Cleveland | Ohio |
| United States | UM Sylvester at Deerfield Beach | Deerfield Beach | Florida |
| United States | Duke University Health System | Durham | North Carolina |
| United States | Houston Methodist Hospital | Houston | Texas |
| United States | Altman Clinical Translational Research institute | La Jolla | California |
| United States | Altman Clinical Translational Research Institute | La Jolla | California |
| United States | UCSD Clinical and Translational Research Institute, Investigational Drug Service | La Jolla | California |
| United States | UCSD Sulpizio Cardiovascular Center | La Jolla | California |
| United States | Cedars-Sinai Medical Care Foundation | Los Angeles | California |
| United States | Cedars-Sinai Medical Center | Los Angeles | California |
| United States | Cedars-Sinai Medical Center, Investigational Drug Pharmacy Services | Los Angeles | California |
| United States | University of Miami Hospital & Clinics | Miami | Florida |
| United States | Vanderbilt University Medical Center | Nashville | Tennessee |
| United States | Ochsner Medical Center | New Orleans | Louisiana |
| United States | Columbia University Medical Center Research Pharmacy | New York | New York |
| United States | Columbia University Medical Center/Clinical Cardiovascular Research Laboratory for the Elderly | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital | New York | New York |
| United States | Mount Sinai Doctors Faculty Practice | New York | New York |
| United States | New York University Hospitals | New York | New York |
| United States | The Mount Sinai Hospital Department of Pharmacy | New York | New York |
| United States | Newark Beth Israel Medical Center | Newark | New Jersey |
| United States | Advocate Christ Medical Centre | Oak Lawn | Illinois |
| United States | Penn Presbyterian Medical Center | Philadelphia | Pennsylvania |
| United States | Mayo Clinic Arizona - Mayo Clinic Speciality Building | Phoenix | Arizona |
| United States | Mayo Clinic Hospital | Phoenix | Arizona |
| United States | OHSU Center for Health and Healing | Portland | Oregon |
| United States | OHSU Research Pharmacy Services | Portland | Oregon |
| United States | Oregon Health and Science University (OHSU) | Portland | Oregon |
| United States | VCU Medical Center - Ambulatory Care Clinic | Richmond | Virginia |
| United States | VCU Medical Center - Main Hospital | Richmond | Virginia |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | Mayo Clinic Pharmacy Research Supp | Rochester | Minnesota |
| United States | University of Utah,Health Sciences Center | Salt Lake City | Utah |
| United States | UCSF Cardiovascular Care and Prevention Center | San Francisco | California |
| United States | Mayo Clinic Arizona - Mayo Clinic Building | Scottsdale | Arizona |
| United States | Virginia Mason Medical Center | Seattle | Washington |
| United States | Stanford University Hospital and Clinics | Stanford | California |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States, Belgium, Brazil, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations | 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 | All-Cause Mortality | 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 | |
| Secondary | Frequency of Cardiovascular-Related Hospitalizations | 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 | |
| Secondary | Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at 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 | |
| Secondary | Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at 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 | |
| Secondary | Number of Participants With Cardiovascular-Related Mortality | 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 | |
| Secondary | Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1 | TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis. | Month 1 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
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| Completed |
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Phase 3 |