Transthyretin-associated Amyloidosis With Polyneuropathy Clinical Trial
Official title:
The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis
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; NT-pro-BNP and
troponin I levels will be measured at Baseline, Weeks 2 and 6, and Months 3, 6, and 12.
Pharmacokinetic measurements will be made using samples collected at Baseline, Week 6, and
Months 6 and 12.
Safety and tolerability will be assessed throughout the study based on vital signs, physical
examinations, ECG, echocardiography, 24-hour Holter monitoring, clinical laboratory tests
(hematology, serum chemistry, and urinalysis), and monitoring adverse events and concomitant
medication use.
Day 1 will be defined as administration of the first dose of study drug. Clinic Visits will
be conducted during Screening (Days -30 to -1) and at Baseline (Day 0), and Week 2, and Week
6, and Months 3, 6, and 12 (± 2 weeks of the scheduled date for post-Baseline visits).
Monthly telephone contacts (+ 1 week of the scheduled date) will be made during months in
which no investigative site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for
assessment of adverse events and concomitant medications. A final telephone contact to
assess adverse events and concomitant medication usage will be made 30 days after the last
dose of study drug.
Patients who discontinue from the study at any time following enrollment will have a final
visit performed, including all safety assessments, at the time of discontinuation. Any
patient discontinuing after the Month 6 visit will also have all exploratory assessments
performed.
n/a
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment