An Extension of Study Fx-005 Evaluating Long-Term Safety And Clinical Outcomes Of Fx-1006A In Patients With Transthyretin Amyloid Polyneuropathy
Condition: Familial Amyloid Polyneuropathy; ATTR-PN
MeSH terms: Polyneuropathies; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Amyloidosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study is designed to determine the long-term safety and tolerability of Fx-1006A as well
      as the effects of Fx-1006A on clinical outcomes in patients with ATTR-PN.

      All patients who enroll in this extension study will receive once-daily oral 20 mg Fx-1006A
      for 12 months; therefore, patients randomized to placebo in Study Fx-005 will cross over to
      active drug (Fx-1006A 20 mg) during this study. However, patients and their families as well
      as clinical Investigators and their clinical site staff will remain blinded to the original
      Fx-005 treatment assignment. It is intended that there will be no interruption in study
      medication administration between the two studies. The majority of safety and clinical
      outcomes assessments will be identical to those evaluated in Study Fx-005. Additional
      assessments for this open-label extension study include 24-hour Holter monitoring and skin
      biopsy for IENF; patients will be required to provide written informed consent to participate
      in this open-label extension study prior to having these additional procedures performed.

      The values obtained from procedures and evaluations conducted during the Month 18 visit of
      Study Fx-005 will be used as the Baseline values for this open-label extension study. The
      Baseline assessments of IENF and Holter monitoring may be conducted at either day of the
      Month 18 visit days of Study Fx-005, but prior to the first Fx-1006A dose in this open-label
      extension study. Clinic Visits will be conducted at Week 6 (± 2 days), and Month 3 (± 1
      week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Monthly telephone contacts (± 1 week of
      the scheduled date) will be made during months in which no investigative site visits are
      scheduled (Months 2, 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and
      concomitant medications.

      Neurological evaluation by NIS-LL will be performed at Months 6 and 12. The NIS-LL will be
      assessed by utilizing the average of two successive NIS-LL clinical assessment scores
      obtained at least 24 hours apart within a one week period for each study visit. A dedicated
      neurologist will be required to perform NIS-LL scoring across all time-points for each
      individual patient enrolled in the study.

      Quality of life utilizing the Norfolk QOL-DN will be assessed at Months 6 and 12 (based on
      the total score as well as the five individual domains of the questionnaire).

      QST (utilizing CASE IV), NCS, HRDB, mBMI, and echocardiography will be conducted at Months 6
      and 12. Holter monitoring will be conducted at Baseline and Months 6 and 12. Biopsies for
      IENF will be obtained at Baseline only. Assessments of troponin I and NT-pro-BNP levels will
      be made at each study visit.

      Blood samples for pharmacokinetic assessments (Fx-1006A concentrations as well as calculated
      steady-state parameters) and pharmacodynamic assessments (TTR stabilization) will be
      collected at Week 6 and Months 6 and 12.

      Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG,
      blood and urine samples for clinical laboratory tests (serum chemistry, hematology,
      coagulation panel, urinalysis, and urine pregnancy testing), adverse events, and concomitant
      medications will be assessed at each study visit. Eye examinations (including fundal
      photography) will be conducted at Months 6 and 12. Abbreviated physical examinations will be
      conducted at Week 6, and Months 3 and 6, and a complete physical examination will be
      conducted at Month 12.

      All patients will be contacted by telephone 30 days (± 1 week) after the last dose of study
      medication for assessment of adverse events and concomitant medications.

      Patients who complete the Month 12 visit of this open-label study may be allowed to continue
      receiving Fx-1006A under a compassionate use program.

      Patients who discontinue from the study at any time after enrollment (i.e., early
      termination) will have final safety assessments performed at the time of discontinuation. Any
      patient discontinuing after the Month 6 visit will have all safety and clinical outcomes
      assessments scheduled for the Month 12 visit performed.
    


Intervention name(s): Fx-1006A
Intervention type(s): Drug
Intervention description(s): Fx-1006A 20mg soft gelatin capsule administered orally once daily (at the same time each day) for 12 months.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: FAP; Familial Amyloid Polyneuropathy; ATTR-PN; transthyretin; TTR; amyloid; polyneuropathy; familial; hereditary; amyloidosis; FoldRx