A Study to Investigate AG-236 in Subjects ≥18 Years of Age With Polycythemia Vera

NCT07859423 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: AG236-C-0022026-527243-18-00
• Study Type: interventional
• Target: 245
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical trial is a Phase 2/3 study that will determine the recommended dose and dose regimen of AG-236 and evaluate the efficacy, safety, and pharmacokinetics of AG-236 in polycythemia vera (PV) by testing how well AG-236 works compared to placebo to increase the number of subjects with no phlebotomy and absence of phlebotomy eligibility over a 13-week period. In addition, the long-term effect of AG-236 on efficacy and safety will be explored in an open-label extension portion.

Conditions

Polycythemia Vera

Outcome Measures

Primary Outcomes (1)

• Phase 2 and Phase 3: Percentage of Subjects With No Phlebotomy and Absence of Phlebotomy Eligibility

  Week 13 Through Week 26

Secondary Outcomes (21)

• Phase 2 and Phase 3: Number of Phlebotomies During the Double-blind Period

  Up to Week 26

• Phase 2: Percentage of Subjects Achieving Hematocrit (HCT) Response During the Double-blind Period

  Up to Week 26

• Phase 2 and Phase 3: Time to First HCT ≥45%

  Up to Week 26

• Phase 2 and Phase 3: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Week 130

• Phase 2 and Phase 3: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of AG-236

  Each dose occasion from Day 1 to Week 52

Study Arms (7)

Phase 2: AG-236 Dose X

EXPERIMENTAL

Subjects will receive AG-236 Dose X, administered subcutaneously (SC), according to the assigned dosing regimen, along with placebo administered SC as needed to maintain the blind in the double-blind period and will receive the same assigned AG-236 dose according to the protocol-defined regimen if they opt to participate in the extension period.

Drug: AG-236; Drug: Placebo

Phase 2: AG-236 Dose Y

EXPERIMENTAL

Subjects will receive AG-236 Dose Y, administered SC, according to the assigned dosing regimen, along with placebo administered SC as needed to maintain the blind in the double-blind period and will receive the same assigned AG-236 dose according to the protocol-defined regimen if they opt to participate in the extension period.

Drug: AG-236; Drug: Placebo

Phase 2: AG-236 Dose Z

EXPERIMENTAL

Subjects will receive AG-236 Dose Z, administered SC, according to the assigned dosing regimen, along with placebo administered SC as needed to maintain the blind in the double-blind period and will receive the same assigned AG-236 dose according to the protocol-defined regimen if they opt to participate in the extension period.

Drug: AG-236; Drug: Placebo

Phase 2: AG-236 Dose ZZ

EXPERIMENTAL

Subjects will receive AG-236 Dose ZZ, administered SC, according to the assigned dosing regimen in the double-blind period, and will receive the same assigned AG-236 dose according to the protocol-defined regimen if they opt to participate in the extension period.

Drug: AG-236

Phase 2: Placebo

PLACEBO COMPARATOR

Subjects will receive placebo administered SC, according to the assigned dosing regimen in the double-blind period and will be randomized to receive AG-236 Dose X, Y, or Z if they opt to participate in the extension period.

Drug: Placebo

Phase 3: AG-236

EXPERIMENTAL

Subjects will receive AG-236, administered SC at the dose and dose regimen selected for Phase 3 for 26 weeks in the double-blind period. Subjects who complete the double-blind period of the study will be eligible to continue receiving AG-236 in the open-label extension period.

Drug: AG-236

Phase 3: Placebo

PLACEBO COMPARATOR

Subjects will receive placebo administered SC at the dose and dose regimen selected for Phase 3 for 26 weeks in the double-blind period. Subjects who complete the double-blind period of the study will be eligible to continue receiving AG-236 in the open-label extension period.

Drug: Placebo

Interventions

AG-236 DRUG

SC Injection

Phase 2: AG-236 Dose X; Phase 2: AG-236 Dose Y; Phase 2: AG-236 Dose Z; Phase 2: AG-236 Dose ZZ; Phase 3: AG-236

Placebo DRUG

SC Injection

Phase 2: AG-236 Dose X; Phase 2: AG-236 Dose Y; Phase 2: AG-236 Dose Z; Phase 2: Placebo; Phase 3: Placebo

Eligibility Criteria

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

You may qualify if:

• PV diagnosis according to 2022 World Health Organization (WHO) criteria.
• Phlebotomy requirements:
• At least 3 documented phlebotomies in the 6 months before randomization or at least 5 documented phlebotomies in the 12 months before randomization.
• and
• At least 1 documented phlebotomy within the 3 months before randomization.
• No phlebotomy within 6 days before randomization (not including the day of phlebotomy and the day of randomization in the 6-day count).
• Cytoreductive therapy is allowed at randomization, but the subject must be on a stable regimen for at least 2 months prior (or at least 6 months with interferons) with no planned change in cytoreductive dose.
• Subjects on phlebotomy alone and no cytoreductive therapy at randomization must have stopped prior treatment at least 2 months prior (at least 6 months for interferons).

You may not qualify if:

• Use of any investigational or marketed N-acetylgalactosamine (GalNAc) targeting product less than 48 weeks before randomization or not recovered from effects of prior administration of any investigational or marketed GalNAc targeting product taken more than 48 weeks before randomization.
• Currently receiving treatment with a hepcidin mimetic; the last dose must have been administered ≥6 months before randomization.
• Currently receiving treatment with or history of any use of TMPRSS6 targeting molecules (antisense oligonucleotide \[ASO\], siRNA, antibodies) before randomization.
• Clinically significant, active and/or uncontrolled hepatobiliary, renal, cardiac, or pulmonary disease.
• Prior malignancy in the last 5 years, except for curatively treated basal cell carcinoma or non-melanoma skin tumors, curatively treated carcinoma in situ of the cervix or breast, or localized prostate cancer.
• Clinically significant thrombosis within 2 months before randomization.
• Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Polycythemia Vera

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Central Study Contacts

Agios Medical Affairs

CONTACT

08332288474; medinfo@agios.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2026
• First Posted: October 5, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2032
• Last Updated: October 5, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share