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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

Tracking Information
First Submitted Date  ICMJE November 14, 2013
First Posted Date  ICMJE November 26, 2013
Last Update Posted Date May 7, 2018
Actual Study Start Date  ICMJE December 9, 2013
Actual Primary Completion Date February 7, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01994889 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
  • 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.
  • 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).
  • Cardiovascular-related mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths adjudicated as being related to cardiovascular causes.
  • 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.
  • All-cause mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths in the study.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy
Official Title  ICMJE 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)
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.
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  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Transthyretin (TTR) Amyloid Cardiomyopathy
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo in soft gel capsules administered once a day for 30 months
Study Arms
  • Experimental: Tafamidis - 20 mg
    Active Treatment-Low dose
    Intervention: Drug: Tafamidis
  • Experimental: Tafamidis - 80 mg
    Active Treatment-High Dose
    Intervention: Drug: Tafamidis
  • Placebo Comparator: Placebo
    Placebo control
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2018)
441
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2013)
400
Actual Study Completion Date February 7, 2018
Actual Primary Completion Date February 7, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   Czechia,   France,   Germany,   Italy,   Japan,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01994889
Other Study ID Numbers  ICMJE B3461028
2012-002465-35 ( EudraCT Number )
ATTR-ACT ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP