Safety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis

Summary

This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP). Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

Timeline

Start

2007-01

Primary completion

2009-05

Completion

2009-05

Outcome

Met primary endpoint

paper Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo PMID 28393570 ↗

Publications

• Merlini G, Coelho T, Waddington Cruz M, Li H, Stewart M, Ebede B. Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Neurol Ther. 2020 Jun;9(1):105-115. doi: 10.1007/s40120-020-00180-w. Epub 2020 Feb 27.
• Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH. A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy. Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27.
• Amass L, Li H, Gundapaneni BK, Schwartz JH, Keohane DJ. Influence of baseline neurologic severity on disease progression and the associated disease-modifying effects of tafamidis in patients with transthyretin amyloid polyneuropathy. Orphanet J Rare Dis. 2018 Dec 17;13(1):225. doi: 10.1186/s13023-018-0947-7.
• Gundapaneni BK, Sultan MB, Keohane DJ, Schwartz JH. Tafamidis delays neurological progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2018 Mar;25(3):464-468. doi: 10.1111/ene.13510. Epub 2017 Dec 26.
• Keohane D, Schwartz J, Gundapaneni B, Stewart M, Amass L. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Mar;24(1):30-36. doi: 10.1080/13506129.2017.1301419. Epub 2017 Apr 10.
• Waddington Cruz M, Amass L, Keohane D, Schwartz J, Li H, Gundapaneni B. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy. Amyloid. 2016 Sep;23(3):178-183. doi: 10.1080/13506129.2016.1207163. Epub 2016 Aug 5.

Drugs

Indications