AG-181 for Healthy Subjects

Overseen By Agios Medical Affairs

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Agios Pharmaceuticals, Inc.

Must not be taking: Prescription drugs, OTC medication

Disqualifiers: Pregnancy, Drug allergy, Alcohol, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates AG-181, a new treatment, to determine its safety and behavior in the body. Participants will take the treatment once or twice daily, with some taking it before or after eating to assess the impact of food. This study targets healthy individuals without significant health issues or allergies, who are willing to avoid caffeine and alcohol during the trial. Participants must also avoid certain foods and medications and should not have used tobacco or donated blood recently. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

Yes, participants must stop using prescription drugs at least 2 weeks before the first dose of the study drug and over-the-counter medications (except routine vitamins) 7 days before, unless the study team agrees it's not clinically relevant.

Is there any evidence suggesting that AG-181 is likely to be safe for humans?

Research shows that AG-181 is currently being tested for safety in humans. In earlier studies, no serious side effects were linked to AG-181. While some participants might have experienced mild reactions, nothing severe was directly associated with the treatment.

The study is in an early stage, focusing on safety and how the body processes the drug. Researchers remain vigilant for any signs of problems. Although specific details on side effects weren't provided, the main goal is to determine if healthy individuals can tolerate AG-181 without major issues.

This phase involves careful safety evaluation, and the results will guide future use of the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care, which often involves well-known medications like NSAIDs or corticosteroids, AG-181 stands out by potentially offering a new mechanism of action. Researchers are excited about AG-181 because it is being tested in healthy subjects to understand its safety and how it behaves in the body, which suggests it might be different from existing treatments. This drug is being administered in both single and multiple ascending doses to explore its effects under various conditions, including food interactions, which could provide insights into optimizing its effectiveness and minimizing side effects. These features make AG-181 a promising candidate for potentially expanding treatment options.

What evidence suggests that AG-181 could be effective?

This trial will study AG-181 in healthy subjects. Research has shown that AG-181 may help treat certain health issues. In studies with individuals who have Crohn's Disease (CD), 18 to 48% of participants experienced a reduction or disappearance of symptoms after four weeks. Additionally, 25 to 41% of these participants remained symptom-free for a period. These results suggest that AG-181 might help manage symptoms in similar conditions by targeting specific areas in the gut. However, further research is needed to fully understand its potential benefits and effectiveness. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy individuals who want to participate in a study testing the safety of a new medication, AG-181. The study will involve taking single or multiple doses of the drug with and without food to see how it's absorbed and tolerated.

Inclusion Criteria

Body mass index in the range of 18.0 to 30.0 kilograms per square meter (kg/m^2)

All values for hematology and clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations, as judged by the Investigator

For women of childbearing potential (WOCBP), have a negative serum or urine pregnancy test at Screening and during admission to the clinic

Exclusion Criteria

History of long-QT syndrome, torsade de pointes, or any risk factors for torsades de pointes in the opinion of the investigator

Use of tobacco or nicotine products in the 48 hours (2 days) prior to administration of the first dose of study drug

Use of any investigational drug or device within 30 days before administration of the first dose of study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Single Ascending Dose (SAD)

Participants receive a single oral dose of AG-181 or placebo under fasted conditions

1 day

1 visit (in-person)

Multiple Ascending Dose (MAD)

Participants receive AG-181 or placebo twice daily for 13 days and a single dose on Day 14 under fasted conditions

14 days

Daily visits (in-person)

Food Effect Study

Participants receive single oral doses of AG-181 under fasted and fed conditions, separated by a 72-hour washout period

2 periods of 1 day each, separated by 72 hours

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AG-181

Trial Overview AG-181 is being tested in this trial. Participants will take either AG-181 or a placebo (a pill without any active drug) to compare effects. The study has three parts: one for single doses, another for multiple doses, and a third part to see how food affects the drug's absorption.

How Is the Trial Designed?

Group I: Part 3: Food Effect - Sequence 2: BA Experimental Treatment 1 Intervention

Participants will receive a single oral dose of AG-181 on Day 1 of Period 1 under fed (high fat meal) condition (B) followed by single oral dose of AG-181 on Day 1 of Period 2 under fasted condition (A). Each period will be separated by a washout period of 1 week.

Group II: Part 3: Food Effect - Sequence 1: AB Experimental Treatment 1 Intervention

Participants will receive single oral dose of AG-181 on Day 1 of Period 1 under fasted condition (A) followed by single oral dose of AG-181 on Day 1 of Period 2 under fed (high fat meal) condition (B). Each period will be separated by a washout period of 1 week.

Group III: Part 2: Multiple Ascending Dose (MAD) Experimental Treatment 2 Interventions

Participants will receive a range of doses of AG-181 or placebo twice daily (BID) for 13 days and a single dose on Day 14 under fasted conditions.

Group IV: Part 1: Single Ascending Dose (SAD) Experimental Treatment 2 Interventions

Participants will receive a range of doses of AG-181 or placebo, orally, once on Day 1. AG-181 will be given under fasted conditions.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Published Research Related to This Trial

A study involving 19 healthy male volunteers found that KC-404 sustained release tablets and capsules have similar pharmacokinetic profiles, indicating they are bioequivalent.

The relative bioavailability of the KC-404 sustained release tablets was found to be 102.6%, suggesting that they are effectively absorbed in the body just like the capsules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and relative bioavailability of KC-404 sustained release tablets in healthy volunteers]. Li, T., Pang, Y., Wang, Z., et al.[2012]

In a study involving 62 healthy volunteers, the maximum tolerated dose of astragalosides injection (AGI) was determined to be 600 mL for a single dose and 400 mL for multiple doses over 7 days, indicating a safe range for future clinical trials.

The study reported 40 adverse events, primarily mild, including abnormal liver function and low blood potassium, suggesting that while AGI is generally well-tolerated, monitoring for specific side effects is necessary in further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and Tolerance of Healthy People to Injection of Astragalosides-a New Drug for Coronary Heart Disease]. Zou, C., Liu, F., Jiang, M., et al.[2018]

A pharmacokinetic and pharmacodynamic model based on cynomolgus monkey data was successfully developed to predict a safe starting dose of AMG 181, an anti-α 4 β 7 antibody for inflammatory bowel diseases, with a starting dose of 0.7 mg in humans.

The model predicted that this starting dose would achieve significant receptor occupancy while maintaining safety, as confirmed by matching predictions with actual human pharmacokinetic data from initial clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of clinical pharmacokinetics of AMG 181, a human anti-α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases. Li, H., Köck, K., Wisler, JA., et al.[2018]

SPH3127 demonstrated a dose-dependent increase in exposure and effectively suppressed plasma renin activity by up to 90% for 24 hours, indicating its potential efficacy in managing conditions related to renin activity.

The drug was well tolerated among healthy individuals, with only mild adverse events reported in 29.2% of single-dose and 33.3% of multiple-dose participants, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Jing, S., Xu, R., Yang, K., et al.[2021]

TAK-357, a potential treatment for Alzheimer's disease, showed a long half-life in plasma and high distribution to adipose tissues in non-clinical studies with rats and dogs, indicating prolonged presence in the body after administration.

The primary route of elimination for TAK-357 was through metabolism, and its slow release from adipose tissues contributes to its extended half-life, suggesting that body weight changes may influence its plasma levels during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disposition of the Highly Fat Distributed Compound 1-(4-Methoxyphenyl)-4-(2,2,4,6,7-Pentamethyl -2,3-Dihydro-1-Benzofuran-5-yl)Piperazine (TAK-357) in Rats and Dogs. Goto, A., Moriya, Y., Mandai, T., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06286033

Single and Multiple Ascending Dose Study and Food Effect ... The primary purpose of this study is to assess the safety and tolerability of AG-181 in healthy participants after oral administration of single ascending dose ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4256621/

Clinical pharmacology of AMG 181, a gut-specific human anti ... For example, in RCTs for treating CD, the overall induction of remission rate was 18 to 48% at week 4, with 25 to 41% of those subjects remaining in remission ...

3. trialx.com trialx.com/clinical-trials/listings/286643/a-safety-study-of-single-and-multiple-doses-of-ag-181-in-healthy-participants/?&radius=10&place=A&user_country=Concord%20N

A Safety Study of Single and Multiple Doses of AG-181 ... The primary purpose of this study is to assess the safety and tolerability of AG-181 in healthy participants after oral administration of single ...

4. gurufocus.com gurufocus.com/news/3178056/agios-agio-unveils-promising-mitapivat-data-at-ash-2025

Agios (AGIO) Unveils Promising Mitapivat Data at ASH 2025 One analysis reveals that 77.8% of patients with alpha-thalassemia treated with mitapivat achieved a reduction in transfusions, significantly ...

5. policylab.us policylab.us/clinical-trials/l/utah/condition/healthy

Healthy Paid Clinical Trials in Utah - Policy Lab GLP-1 medications are scientifically backed to help individuals achieve significant weight loss—on average, 15-20% of body weight within a year. As a valued ...

6. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-announces-key-2025-milestones-innovative-rare-disease

Agios Announces Key 2025 Milestones for Innovative Rare ... Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06286033/a-safety-study-of-single-and-multiple-doses-of-ag-181-in-healthy-participants?state=UT&city=Salt%20Lake%20County

Single and Multiple Ascending Dose Study and Food Effect ... The primary purpose of this study is to assess the safety and tolerability of AG-181 in healthy participants after oral administration of single ascending dose ...

8. synapse.patsnap.com synapse.patsnap.com/drug/3411dc89e9f646c89189fd8487ac48ab

AG-181 - Drug Targets, Indications, Patents A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AG-181 in Healthy Participants.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/216540Orig1s000IntegratedR.pdf

216540Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Integrated Review. Table 1. Application Information. Application type. NDA. Application number(s). 216540. Priority or standard. STANDARD.