Ignite Creation Date:
2025-12-24 @ 10:34 PM
Ignite Modification Date:
2025-12-29 @ 10:26 PM
Study NCT ID:
NCT04882735
Status:
WITHDRAWN
Last Update Posted:
2024-09-19
First Post:
2021-04-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy and Safety of Acoramidis (AG10) in Subjects with Transthyretin Amyloid Polyneurophathy (ATTRibute-PN)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D028227', 'term': 'Amyloid Neuropathies, Familial'}, {'id': 'D000686', 'term': 'Amyloidosis'}, {'id': 'D000544', 'term': 'Alzheimer Disease'}, {'id': 'D011115', 'term': 'Polyneuropathies'}, {'id': 'D028226', 'term': 'Amyloidosis, Familial'}, {'id': 'C567782', 'term': 'Amyloidosis, Hereditary, Transthyretin-Related'}], 'ancestors': [{'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D017772', 'term': 'Amyloid Neuropathies'}, {'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D057165', 'term': 'Proteostasis Deficiencies'}, {'id': 'D003704', 'term': 'Dementia'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000731204', 'term': 'attruby'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': "Sponsor's decision to cancel study", 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2021-09-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-01', 'completionDateStruct': {'date': '2026-10', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-09-10', 'studyFirstSubmitDate': '2021-04-29', 'studyFirstSubmitQcDate': '2021-05-06', 'lastUpdatePostDateStruct': {'date': '2024-09-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-05-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-09', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change from baseline to Month 18 in mNIS+7', 'timeFrame': '18 Months', 'description': '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.'}, {'measure': 'Safety: TESAEs will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}, {'measure': '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)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}, {'measure': 'Safety: Adverse Events will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}, {'measure': '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)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}, {'measure': '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)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}, {'measure': '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)', 'timeFrame': '60 Months', 'description': 'To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)'}], 'secondaryOutcomes': [{'measure': 'Change from baseline to Month 18 in Norfolk QOL-DN', 'timeFrame': '18 Months', 'description': 'To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN)'}, {'measure': 'Change from baseline to Month 18 in mBMI', 'timeFrame': '18 Months', 'description': 'To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Modified body mass index (mBMI)'}, {'measure': 'Change from baseline to Month 18 in COMPASS-31', 'timeFrame': '18 Months', 'description': 'To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Composite Autonomic Score (COMPASS-31)'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['TTR', 'ATTR-PN', 'Familial ATTR-PN', 'Amyloidosis', 'Amyloid', 'Transthyretin', 'Polyneuropathy', 'TTR-mediated amyloidosis', 'Amyloidosis, hereditary', 'Familial Amyloid Polyneuropathies', 'Amyloidosis, Hereditary, Transthyretin-Related'], 'conditions': ['Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy']}, 'descriptionModule': {'briefSummary': 'Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)', 'detailedDescription': '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.\n\nIn 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).\n\nIn this study Eidos, a BridgeBio Company, is researching the investigational drug acoramidis (AG10) hydrochloride (HCl) 800mg administered orally twice a day. Through the study, Eidos/BridgeBio wants to evaluate the efficacy and safety of acoramidis in patients with ATTR-PN.\n\nThe primary outcome of the study is to determine the efficacy of acoramidis in the treatment of subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN).\n\nAt the end of 18 months, participants will be eligible to continue to receive acoramidis to evaluate the long-term safety and tolerability of acoramidis.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female ≥18 to ≤90 years of age;\n* 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;\n* Have an NIS of 5 to 130 (inclusive) during Screening;\n* 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;\n* 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;\n* Have an anticipated survival of \\>2 years in the opinion of the investigator;\n* Have Karnofsky performance status ≥60 %.\n\nExclusion Criteria:\n\n* 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;\n* Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, due to autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;\n* Has Vitamin B-12 levels below the lower limit of normal (LLN) at Screening;\n* Has clinical evidence of untreated hyperthyroidism or hypothyroidism;\n* Has leptomeningeal TTR amyloidosis;\n* Has Type 1 diabetes;\n* Has had Type 2 diabetes for ≥5 years;\n* Has a documented case of hepatitis B or C at Screening;\n* Known history of human immunodeficiency virus (HIV) infection;\n* Has NYHA heart failure classification \\>Class II;\n* Had acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke within 90 days prior to Screening;\n* Has estimated glomerular filtration rate (eGFR) by Modification of Diet for Renal Disease (MDRD) formula \\<30 mL/min/1.73 m2 at Screening;\n* 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;\n* 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;\n* Has known hypersensitivity to acoramidis, its metabolites, or formulation excipients.\n* 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.'}, 'identificationModule': {'nctId': 'NCT04882735', 'briefTitle': 'Efficacy and Safety of Acoramidis (AG10) in Subjects with Transthyretin Amyloid Polyneurophathy (ATTRibute-PN)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Eidos Therapeutics, a BridgeBio company'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'AG10-334'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Acoramidis HCI 800 mg (two 400mg tablets)', 'description': 'TTR stabilizer administered orally twice daily (BID)', 'interventionNames': ['Drug: Acoramidis']}], 'interventions': [{'name': 'Acoramidis', 'type': 'DRUG', 'otherNames': ['AG10'], 'description': 'TTR stabilizer administered orally twice daily (BID)', 'armGroupLabels': ['Acoramidis HCI 800 mg (two 400mg tablets)']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Mark McGovern, RN, CCRN', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Eidos Therapeutics, a BridgeBio company'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Eidos Therapeutics, a BridgeBio company', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}