PhenylketonuriaPhase 1NCT07241234
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
A Phase 1 study testing AG-181 in people with Phenylketonuria, run by Agios Pharmaceuticals, Inc. at 5 sites in 2 countries.
Trial summary
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU). Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- AG-181
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 17 Apr 2026to 17 Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 2 countries
United States3 sites, 3 recruiting
- Recruiting
University of Texas Southwestern Medical Center (UTSW)
Dallas, Texas, 75390
- Recruiting
Indiana University
Indianapolis, Indiana, 46202
- Recruiting
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Poland2 sites, 2 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne (Medical University of Gdansk)
Gdansk, Pomeranian Voivodeship, 80-952
- Recruiting
Centrum Wsparcia Badań Klinicznych Pomorskiego Uniwersytetu Medycznego w Szczecinie
Szczecin, West Pomeranian Voivodeship, 71-252
About this study
Official title: A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
- Conditions
- Phenylketonuria
- Being tested
- AG-181
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-181Drug
AG-181 film-coated tablets
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: AG-181 | Experimental | Subjects will receive AG-181 from Day 1 to Day 28. Receives: Drug: AG-181 |
| Cohort 2 (Optional Cohort): AG-181 | Experimental | Subjects will receive AG-181. Receives: Drug: AG-181 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug
Measured: Up to Day 42
Secondary outcomes (7)
Plasma Concentration of AG-181
Measured: Up to Day 28
Maximum Concentration (Cmax) of AG-181
Measured: Up to Day 28
Time to Maximum (Peak) Concentration (Tmax) of AG-181
Measured: Up to Day 28
Area Under the Concentration-Time Curve (AUC) of AG-181
Measured: Up to Day 28
Apparent Total Body Clearance (CL/F) of AG-181
Measured: Up to Day 28
Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181
Measured: Up to Day 28
Change From Baseline in Phenylalanine (Phe) Concentration
Measured: Baseline up to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2025
- Study start17 Apr 2026
- Primary completion17 Jan 2028 (estimated)
- Study completion17 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07241234
- Sponsor's protocol ID
- AG181-C-002
- Other IDs
- 2025-522630-31-00, 2025
- Status last verified
- Sep 2026
- First submitted
- 17 Nov 2025
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria
- ClinicalTrials.gov ID
- NCT07241234
- Acronym / sponsor ID
- AG181-C-002
- Conditions
- Phenylketonuria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Apr 2026 (actual)
- Primary completion
- 17 Jan 2028 (estimated)
- Study completion
- 17 Jan 2028 (estimated)
- First posted
- 21 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: AG-181 | Experimental | Drug: AG-181Subjects will receive AG-181 from Day 1 to Day 28. |
| Cohort 2 (Optional Cohort): AG-181 | Experimental | Drug: AG-181Subjects will receive AG-181. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AG-181AG-181 film-coated tablets | Drug | Cohort 1: AG-181, Cohort 2 (Optional Cohort): AG-181 |
Primary outcome
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
7 secondary outcomes
Plasma Concentration of AG-181
Time frame: Up to Day 28
Maximum Concentration (Cmax) of AG-181
Time frame: Up to Day 28
Time to Maximum (Peak) Concentration (Tmax) of AG-181
Time frame: Up to Day 28
Area Under the Concentration-Time Curve (AUC) of AG-181
Time frame: Up to Day 28
Apparent Total Body Clearance (CL/F) of AG-181
Time frame: Up to Day 28
Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181
Time frame: Up to Day 28
Change From Baseline in Phenylalanine (Phe) Concentration
Time frame: Baseline up to Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG-181 in people with Phenylketonuria, run by Agios Pharmaceuticals, Inc. at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agios Medical Affairs (833-228-8474, medinfo@agios.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.