Efficacy and Safety of Acoramidis (AG10) in Subjects with Transthyretin Amyloid Polyneurophathy (ATTRibute-PN)

Trial details

Who runs it

Eidos Therapeutics, a BridgeBio company

Trial code

NCT04882735

Record updated

19 September 2024

Original description

Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)Read full original descriptionShow less

A Phase 3, Open-Label, Multicenter, Single-Arm Study to Evaluate the Efficacy and Safety of Acoramidis in Subjects with Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Study)

Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)

Inclusion: Male or female ≥18 to ≤90 years of age; Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIb) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical examination 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 enrollment. No genetic testing is needed for subjects who are recipients of domino liver transplants; Have an anticipated survival of >2 years in the opinion of the investigator; Have Karnofsky performance status ≥60 %.

Exclusion: 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; Had acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke within 90 days prior to Screening; Is currently undergoing treatment for ATTR-PN with tafamidis, or patisiran, inotersen, or other knockdown agents, marketed drug products lacking a labeled 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 14 days for tafamidis or 90days for patisiran and 180 days for inotersen prior to dosing; Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, due to autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse; Has Type 1 diabetes; Has a documented case of hepatitis B or C at Screening; Known history of 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 the skin or carcinoma in situ of the cervix that has been successfully treated; Has known hypersensitivity to acoramidis, its metabolites, or formulation excipients; Has estimated glomerular filtration rate (eGFR) by Modification of Diet for Renal Disease (MDRD) formula <30 mL/min/1.73 m2 at Screening; Has abnormal liver function tests at Screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >3 × ULN; Has had Type 2 diabetes for ≥5 years; Has Vitamin B-12 levels below the lower limit of normal (LLN) at Screening; Has clinical evidence of untreated hyperthyroidism or hypothyroidism; Has leptomeningeal TTR amyloidosis.

ClinicalTrials.gov NCT04882735