Recruiting
Phase 1

AG-181

Sponsor:

Agios Pharmaceuticals, Inc.

Code:

NCT07241234

Conditions

Phenylketonuria

Eligibility Criteria

Sex: All

Age: 18 - 69

Healthy Volunteers: Not accepted

Interventions

AG-181

Study Details

Brief summary:

The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).

Conditions

Phenylketonuria

Study ID

NCT07241234

Start date

Apr 17, 2026

Status verified date

Aug, 2026

Completion date

Jan 17, 2028

Anticipated

Primary completion date

Jan 17, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 69

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • 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.
  • At least 1 plasma Phe concentration greater than (>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing informed consent.
  • 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.
  • 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.
  • 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.

Key Exclusion Criteria:

  • Prior exposure to AG-181.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Inability to tolerate oral medication.
  • Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening.

Study Design

Enrollment

20 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1: AG-181

Subjects will receive AG-181 from Day 1 to Day 28.

experimental: Cohort 2 (Optional Cohort): AG-181

Subjects will receive AG-181.

Interventions

AG-181

AG-181 film-coated tablets

Primary outcome measure

  • Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug [ Time Frame: Up to Day 42 ]

Central Contacts and Locations

Central contacts

Agios Medical Affairs

833-228-8474medinfo@agios.com

Locations

Indiana University

Recruiting

Indianapolis, Indiana, United States, 46202

UPMC Children's Hospital of Pittsburgh

Recruiting

Pittsburgh, Pennsylvania, United States, 15224

University of Texas Southwestern Medical Center (UTSW)

Recruiting

Dallas, Texas, United States, 75390

More Information

Sponsor

Agios Pharmaceuticals, Inc.

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Agios Pharmaceuticals, Inc. on 2026-08-27.