The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis
Condition: Transthyretin-associated Amyloidosis With Polyneuropathy
MeSH terms: Polyneuropathies; Amyloidosis
Study type: Interventional
Phase: Phase 2

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; 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.
    


Intervention name(s): Fx-1006A
Intervention type(s): Drug
Intervention description(s): During Part 1, patients will receive Fx-1006A 20mg soft gelatin capsules once daily (at the same time each day) for two weeks. During Part 2, patients will receive Fx-1006A 20mg soft gelatin capsules once daily to complete a total of 12 months of dosing
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Transthyretin, TTR, amyloidosis, TTR amyloidosis, polyneuropathy