The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis
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.
Description
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.
Study Design
Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Transthyretin-associated Amyloidosis With Polyneuropathy
Intervention
Fx-1006A
Location
Johns Hopkins Hospital
Baltimore
Maryland
United States
21205
Status
Completed
Source
FoldRx Pharmaceuticals
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00630864
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Amyloidosis, Familial
Diseases in which there is a familial pattern of AMYLOIDOSIS.
Paraneoplastic Polyneuropathy
A diffuse or multifocal peripheral neuropathy related to the remote effects of a neoplasm, most often carcinoma or lymphoma. Pathologically, there are inflammatory changes in peripheral nerves. The most common clinical presentation is a symmetric distal mixed sensorimotor polyneuropathy. (Adams et al., Principles of Neurology, 6th ed, p1334)
Amyloid Neuropathies, Familial
Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. The different clinical types based on symptoms correspond to the presence of a variety of mutations in several different proteins including transthyretin (PREALBUMIN); APOLIPOPROTEIN A-I; and GELSOLIN.
Congo Red
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
Retinol-binding Proteins, Plasma
Retinol binding proteins that circulate in the PLASMA. They are members of the lipocalin family of proteins and play a role in the transport of RETINOL from the LIVER to the peripheral tissues. The proteins are usually found in association with TRANSTHYRETIN.
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