Clinical Trial: The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis

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 Non-V30M Transthyretin Amyloidosis

Brief Summary:

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis.

Strong pre-clinical and clinical evidence support a daily dose of 20 mg of Fx-1006A to be the optimum dose to achieve stabilization of tetrameric TTR in ATTR-PN patients. Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. Safety and exploratory efficacy of Fx-1006A administered once daily for 12 months will also be evaluated in this patient population.

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will receive 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 receiving 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, the patient will be discontinued from the study.

During Part 2, clinical outcomes will be measured at Months 6 and 12, based on NIS, Norfolk QOL-DN, mBMI, NCS, HRDB, SF-36, Karnofsky score, and echocardiography

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: TTR stabilization [ Time Frame: 6 weeks ]

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 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:

  • Incidence of patients experiencing treatment-emergent adverse events [ Time Frame: 12 months ]
  • Incidence of patients experiencing treatment-emergent >/= Grade 3 adverse events [ 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 with treatment-emergent electrocardiogram (ECG) findings considered by the Investigator to be clinically significant [ Time Frame: 12 months ]
  • Incidence of patients with treatment-emergent Holter monitoring 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 adverse events [ Time Frame: 12 months ]
  • Change from Baseline in the Neuropathy Impairment Score (NIS) and NIS-Lower Limb (LL) scores [ Time Frame: 6 and 12 months ]
  • Response to treatment (change from Baseline in the NIS-LL of < 2) [ Time Frame: 6 and 12 months ]
  • Change from Baseline in the total quality of life and five individual domain scores of the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) [ Time Frame: 6 and 12 months ]
  • Change from Baseline in nerve conduction studies (NCS) [ Time Frame: 6 and 12 months ]
  • Change from Baseline in heart rate response to deep breathing (HRDB) [ Time Frame: 6 and 12 months ]
  • Change from Baseline in modified body mass index (mBMI) [ Time Frame: 6 and 12 months ]
  • Change from Baseline in overall quality of life and individual domains of the SF-36 [ Time Frame: 6 and 12 months ]
  • Change from Baseline in echocardiography parameters [ Time Frame: 6 and 12 months ]
  • Change from Baseline in NT-pro-BNP and troponin I levels [ Time Frame: 6 weeks, 3, 6, and 12 months ]
  • Change from Baseline in Karnofsky score [ Time Frame: 6 and 12 months ]


Information By: Pfizer

Dates:
Date Received: February 27, 2008
Date Started: June 2008
Date Completion:
Last Updated: January 9, 2013
Last Verified: January 2013