Efficacy and Safety of AG10 in Subjects with Transthyretin Amyloid Polyneurophathy

Launched by EIDOS THERAPEUTICS, A BRIDGEBIO COMPANY · Jun 1, 2020

Keywords

ClinConnect Summary

\*\* See updated study design under ClinicalTrials.gov Identifier NCT04882735. \*\*

Transthyretin amyloid polyneuropathy (ATTR-PN), also called "Familial Transthyretin-Mediated Amyloid Polyneuropathy (FAP)" is a hereditary condition caused by mutations in the TTR gene. It is estimated that around 10,000 people in the world are affected.

In ATTR-PN, amyloid builds up in the nerves that detect temperature, pain, and touch. Patients with ATTR-PN can experience a loss of sensation, tingling, numbness, or pain in the hands and feet (also called peripheral neuropathy).

In this study Eidos is r...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Be male or female ≥18 to ≤90 years of age;
• • Have Stage I or II symptoms (polyneuropathy disability \[PND\] ≤IIIa) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam findings and/or neurophysiological test findings consistent with the diagnosis of ATTR-PN;
• • Have an NIS of 5 to 130 (inclusive) during screening;
• • Have a nerve conduction studies (NCS) score \[sum of the sural sensory nerve action potential (SNAP), tibial compound muscle action potential (CMAP), ulnar SNAP, ulnar CMAP, and peroneal CMAP\] of ≥2 points during screening. NCS is a component of mNIS+7;
• • Have a mutation consistent with ATTR-PN either documented in medical history or confirmed by genotyping obtained at Screening prior to randomization. \*No genetic testing is needed for subjects who are recipients of domino liver transplants;
• • Have an anticipated survival of ≥2 years
• • Have Karnofsky performance status ≥60 %;
• Exclusion Criteria:
• • Had a prior liver transplantation or is planning to undergo liver transplantation with a wild-type organ graft as treatment for symptomatic ATTR-PN during the study period.
• • Note: Recipients of a "domino" liver transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their graft are allowed under this protocol, as long as re-transplantation to treat ATTR-PN is not planned during the study period and meets all other eligibility criteria;
• • Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
• • Has Vitamin B-12 levels below the lower limit of normal (LLN);
• • Has clinical evidence of untreated hyper/hypothyroidism;
• • Has leptomeningeal TTR amyloidosis;
• • Has Type 1 diabetes;
• • Has had Type 2 diabetes for ≥5 years;
• • Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;
• • Has NYHA heart failure classification \>Class II
• • Had a malignancy within 2 years, except for basal or squamous cell carcinoma of
• • Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or other gene silencing agents, marketed drug products lacking a label indication for ATTR- PN (e.g., diflunisal, doxycycline), natural products or derivatives used as unproven therapies for ATTR-PN (e.g., green tea extract, tauroursodeoxycholic acid \[TUDCA\]/ursodiol), within 14 days, or 90 days for patisiran and 180 days for inotersen prior to dosing. Prior to screening, tafamidis, if already prescribed to potential subjects as part of their established background therapy, is allowed at the labeled dosage and administration of 20 mg/day for the treatment of ATTR-PN with, i in the opinion of the Investigator, evidence of disease progression while on tafamidis treatment