Ignite Creation Date:
2025-12-25 @ 2:36 AM
Ignite Modification Date:
2025-12-26 @ 1:13 AM
Study NCT ID:
NCT07241234
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-11-21
First Post:
2025-11-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Participants With Phenylketonuria
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010661', 'term': 'Phenylketonurias'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2028-01-17', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-17', 'studyFirstSubmitDate': '2025-11-17', 'studyFirstSubmitQcDate': '2025-11-17', 'lastUpdatePostDateStruct': {'date': '2025-11-21', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-11-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2028-01-17', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug', 'timeFrame': 'Up to Day 42'}], 'secondaryOutcomes': [{'measure': 'Plasma Concentration of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Maximum Concentration (Cmax) of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Time to Maximum (Peak) Concentration (Tmax) of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Area Under the Concentration-Time Curve (AUC) of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Apparent Total Body Clearance (CL/F) of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181', 'timeFrame': 'Up to Day 28'}, {'measure': 'Change From Baseline in Phenylalanine (Phe) Concentration', 'timeFrame': 'Baseline up to Day 28'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Phenylketonuria']}, 'descriptionModule': {'briefSummary': 'The primary purpose of this study is to assess the safety and tolerability of AG-181 in participants with Phenylketonuria (PKU).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '69 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Key Inclusion Criteria:\n\n* Diagnosis of PKU, defined as documented presence of 2 mutant alleles in the phenylalanine hydroxylase (PAH) gene, of which at least 1 is the R408W mutation, as determined during Screening per the genotyping performed by the study central genotyping laboratory.\n* At least 1 plasma Phe concentration greater than (\\>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing informed consent.\n* Average concentration of plasma Phe \\> 600 μmol/L in Phe samples taken during Screening, with no individual assessment below 360 μmol/L. Any Phe samples taken after Day -20 will not be included.\n* Body mass index (BMI) greater than or equal to (≥) 18.0 kilograms per meter square (kg/m\\^2) to lesser than or equal to (≤) 35.0 kg/m\\^2 and weight ≥ 50 kilograms (kg) at any time during the Screening Period.\n* Documented approval from a dietitian confirming that the subject can maintain their diet consistent in protein and Phe intake throughout the study as outlined in the Diet Manual.\n\nKey Exclusion Criteria:\n\n* Prior exposure to AG-181.\n* Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥ 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug.\n* Receiving products that are strong inhibitors or strong inducers of cytochrome P450 CYP1A2, CYP2C8, or CYP3A that have not been stopped for ≥ 28 days before administration of the first dose of study drug.\n* Receiving treatment with an acid-reducing agent, including but not limited to proton pump inhibitors and H2 blockers. Short-acting acid-reducing agents such as calcium carbonate are permitted.\n* Any preexisting condition that could (in the opinion of the Investigator) interfere with gastrointestinal anatomy or motility that may disrupt the absorption, metabolism, and/or excretion of the study drug.\n* Any preexisting condition that could (in the opinion of the Investigator) interfere with hepatic or renal function that may disrupt the absorption, metabolism, and/or excretion of the study drug.\n* Inability to tolerate oral medication.\n* Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening.'}, 'identificationModule': {'nctId': 'NCT07241234', 'briefTitle': 'A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Participants With Phenylketonuria', 'organization': {'class': 'INDUSTRY', 'fullName': 'Agios Pharmaceuticals, Inc.'}, 'officialTitle': 'A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria', 'orgStudyIdInfo': {'id': 'AG181-C-002'}, 'secondaryIdInfos': [{'id': '2025-522630-31-00', 'type': 'CTIS'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1: AG-181', 'description': 'Participants will receive AG-181 from Day 1 to Day 28.', 'interventionNames': ['Drug: AG-181']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2 (Optional Cohort): AG-181', 'description': 'Participants will receive AG-181.', 'interventionNames': ['Drug: AG-181']}], 'interventions': [{'name': 'AG-181', 'type': 'DRUG', 'description': 'AG-181 film-coated tablets', 'armGroupLabels': ['Cohort 1: AG-181', 'Cohort 2 (Optional Cohort): AG-181']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Agios Medical Affairs', 'role': 'CONTACT', 'email': 'medinfo@agios.com', 'phone': '833-228-8474'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Agios Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}