Please select the outcome measures that correspond to the clinical trial below.
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; 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.


Options:
A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation (Up to 56 days post first dose)
B: Modified Neuropathy Impairment Score +7 (mNIS+7) (18mo)
C: Val30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline (Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005)); Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 30 (Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 30); Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 66 (Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 66); NonVal30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline (Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201)); NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 12 (Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), Month 12); NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 60 (Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), Month 60); Val30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline (Baseline of B3461020 (Fx-005)); Val30Met Group: Change From B3461020 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 30 (Baseline of B3461020 (Fx-005), Month 30); Val30Met Group: Change From B3461020 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 66 (Baseline of B3461020 (Fx-005), Month 66); NonVal30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline (Baseline of B3461022 (Fx1A-201)); NonVal30Met Group: Change From B3461022 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 12 (Baseline of B3461022 (Fx1A-201), Month 12); NonVal30Met Group: Change From B3461022 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 60 (Baseline of B3461022 (Fx1A-201), Month 60); Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 30 (Month 30 (Baseline of B3461023)); Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 66 (Month 66 (Month 36 of B3461023)); NonVal30Met Group: Karnofsky Performance Scale (KPS) Score at Baseline (Baseline of B3461022 (Fx1A-201)); NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 12 (Baseline of B3461022 (Fx1A-201), Month 12); NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 60 (Baseline of B3461022 (Fx1A-201), Month 60); Val30Met Group: Number of Participants by Ambulation Stage at Baseline (Baseline of B3461020 (Fx-005)); Val30Met Group: Number of Participants by Ambulation Stage at Month 30 (Month 30); Val30Met Group: Number of Participants by Ambulation Stage at Month 66 (Month 66); NonVal30Met Group: Number of Participants by Ambulation Stage at Baseline (Baseline of B3461022 (Fx1A-201)); NonVal30Met Group: Number of Participants by Ambulation Stage at Month 12 (Month 12); NonVal30Met Group: Number of Participants by Ambulation Stage at Month 60 (Month 60)
D: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6 (Week 6)

Answer: D