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

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.

Key Inclusion Criteria: * 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). Key Exclusion Criteria: * 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. Note: Other protocol-defined inclusion/exclusion criteria may apply.