A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria

NCT07241234 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: AG181-C-0022025-522630-31-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug

  Up to Day 42

Secondary Outcomes (7)

• Plasma Concentration of AG-181

  Up to Day 28

• Maximum Concentration (Cmax) of AG-181

  Up to Day 28

• Time to Maximum (Peak) Concentration (Tmax) of AG-181

  Up to Day 28

• Area Under the Concentration-Time Curve (AUC) of AG-181

  Up to Day 28

• Apparent Total Body Clearance (CL/F) of AG-181

  Up to Day 28

Study Arms (2)

Cohort 1: AG-181

EXPERIMENTAL

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

Drug: AG-181

Cohort 2 (Optional Cohort): AG-181

EXPERIMENTAL

Subjects will receive AG-181.

Drug: AG-181

Interventions

AG-181 DRUG

AG-181 film-coated tablets

Cohort 1: AG-181; Cohort 2 (Optional Cohort): AG-181

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

University of Texas Southwestern Medical Center (UTSW)

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Agios Medical Affairs

CONTACT

833-228-8474; medinfo@agios.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 21, 2025
• Study Start: April 21, 2026
• Primary Completion (Estimated): January 17, 2028
• Study Completion (Estimated): January 17, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)