Clinical Trial: The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy

Brief Summary:

Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy.

The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will self-administer oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue taking daily oral Fx 1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6 (based on TTR stabilization data), the patient will be discontinued from the study. Safety and clinical outcomes will be evaluated during Part 2 of this study.

Two whole blood samples for pharmacodynamic assessments (TTR stabilization) and pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) will be collected at Baseline and Week 6. At Months 6 and 12, two whole blood samples will be collected for pharmacodynamic assessments, and four whole blood samples (two samples per time point) will be collected for pharmacokinetic assessments to be utilized in population pharmacokinetic modeling.

Echocardiography, chest x-ray, cardiac MRI, and 24-hour Holter monitoring will be conducted at Baseline, and Months 6 and 12. Six-minute walk test and quality of life utilizing the Patient Global Assessment, KCCQ, and SF-36 will be assessed at Baseline, and Months 3, 6, and 12. NYHA Classification will be assessed at Baseline, Week 6, and Months 3, 6, and 12. Serum markers of troponin I and T, and N

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6 [ Time Frame: Week 6 ]

TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.


Original Primary Outcome: The primary endpoint of this study is TTR stabilization at Week 6 compared with Baseline, as measured by a validated immunoturbidimetric assay [ Time Frame: 12 months ]

Current Secondary Outcome: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12 [ Time Frame: Month 6, Month 12 ]

TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.


Original Secondary Outcome:

  • The secondary endpoints of this study are TTR stabilization at Months 6 and 12 compared with Baseline, as measured by a validated immunoturbidimetric assay [ Time Frame: 6 and 12 months ]
  • Incidence of patients experiencing treatment-emergent adverse events [ Time Frame: 12 months ]
  • Incidence of patients experiencing treatment-emergent >/= Grade 3 AEs [ Time Frame: 12 months ]
  • Incidence of patients with treatment-emergent echocardiography findings considered by the Investigator to be clinically significant [ Time Frame: 12 months ]
  • Incidence of patients discontinuing from the study because of clinical or laboratory AEs [ Time Frame: 12 months ]
  • Change from Baseline in echocardiographic parameters [ Time Frame: 6 and 12 months ]
  • Change from Baseline in cardiac magnetic resonance imaging (MRI) parameters [ Time Frame: 6 and 12 months ]
  • Change from Baseline in 24-hour Holter monitoring parameters [ Time Frame: 6 and 12 months ]
  • Change from Baseline in the New York Heart Association (NYHA) Classification [ Time Frame: 6 Weeks, 3, 6, and 12 months ]
  • Change from Baseline in chest x-ray parameters [ Time Frame: 6 and 12 months ]
  • Change from Baseline in the Patient Global Assessment [ Time Frame: 3, 6, 12 months ]
  • Change from Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score [ Time Frame: 3, 6, 12 months ]
  • Change from Baseline in the Short Form 36 (SF-36) [ Time Frame: 3, 6, 12 months ]
  • Change from Baseline in troponin I and T, and NT-pro-BNP levels [ Time Frame: 2 weeks, 6 weeks, 3, 6, 12 months ]
  • Change from Baseline in 6-Minute Walk Test [ Time Frame: 6 and 12 months ]


Information By: Pfizer

Dates:
Date Received: June 6, 2008
Date Started: August 2008
Date Completion:
Last Updated: January 4, 2013
Last Verified: January 2013