Efficacy and Safety of AG10 in Subjects with Transthyretin Amyloid Polyneurophathy

NCT04418024 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: AG10-3332018-004670-10
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo 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 (1)

• Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment

  Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.

  18 Months

Study Arms (2)

AG10 800 mg

EXPERIMENTAL

TTR stabilizer administered orally twice daily (BID)

Drug: AG10

Placebo

PLACEBO COMPARATOR

Placebo administered orally twice daily (BID)

Drug: Placebo

Interventions

AG10 DRUG

TTR stabilizer administered orally twice daily (BID)

Also known as: Oral AG10

AG10 800 mg

Placebo DRUG

Non-active control

Also known as: Placebo Oral Tablet

Placebo

Eligibility Criteria

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

You may qualify if:

• 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 %;

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, 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

Sponsors & Collaborators

• Eidos Therapeutics, a BridgeBio company: lead

Study Sites (1)

Eidos Therapeutics

San Francisco, California, 94104, United States

Location

MeSH Terms

Conditions

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

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: June 5, 2020
• Study Start: October 21, 2020
• Primary Completion: March 31, 2024
• Study Completion: April 30, 2024
• Last Updated: September 19, 2024

Record last verified: 2021-06

Locations

US (1)