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

NCT04882735 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: AG10-334
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy

Keywords

TTR; ATTR-PN; Familial ATTR-PN; Amyloidosis; Amyloid; Transthyretin; Polyneuropathy; TTR-mediated amyloidosis; Amyloidosis, hereditary; Familial Amyloid Polyneuropathies; Amyloidosis, Hereditary, Transthyretin-Related

Outcome Measures

Primary Outcomes (7)

• Change from baseline to Month 18 in mNIS+7

  To determine the efficacy of acoramidis in subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN) by evaluating the change in Modified Neuropathy Impairment Score +7 (mNIS+7) from baseline to 18 months.

  18 Months

• Safety: TESAEs will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

• Safety: Adverse Events leading to treatment discontinuation will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

• Safety: Adverse Events will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

• Safety: Incidence of abnormal physical exam will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

• Safety: Incidence of abnormal vital signs will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

• Safety: Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)

  To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)

  60 Months

Secondary Outcomes (3)

• Change from baseline to Month 18 in Norfolk QOL-DN

  18 Months

• Change from baseline to Month 18 in mBMI

  18 Months

• Change from baseline to Month 18 in COMPASS-31

  18 Months

Study Arms (1)

Acoramidis HCI 800 mg (two 400mg tablets)

EXPERIMENTAL

TTR stabilizer administered orally twice daily (BID)

Drug: Acoramidis

Interventions

Acoramidis DRUG

TTR stabilizer administered orally twice daily (BID)

Also known as: AG10

Acoramidis HCI 800 mg (two 400mg tablets)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %.

You may not qualify if:

• 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, due to autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
• 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;
• Has Type 1 diabetes;
• Has had Type 2 diabetes for ≥5 years;
• 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 acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke within 90 days prior to Screening;
• 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;
• 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.

Sponsors & Collaborators

• Eidos Therapeutics, a BridgeBio company: lead

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis; Alzheimer Disease; Polyneuropathies; Amyloidosis, Familial; Amyloidosis, Hereditary, Transthyretin-Related

Interventions

attruby

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Proteostasis Deficiencies; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders

Study Officials

• Mark McGovern, RN, CCRN

  Eidos Therapeutics, a BridgeBio company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 12, 2021
• Study Start: September 8, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 19, 2024

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share