Epetraborole Tablets for Adults With Polycythemia Vera Who Need Blood Removal

Trial details

Who runs it

AN2 Therapeutics, Inc

Trial code

NCT07891533

Record updated

23 October 2026

Original description

This is a Phase 2 trial to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of oral epetraborole tablets for the treatment of adults with phlebotomy-dependent polycythemia vera (PV). The trial is designed to confirm the safety profile of oral epetraborole in the PV patient population and to identify 1 or more oral epetraborole doses for the treatment of phlebotomy-dependent PV. The study consists of an open-label Sentinel Cohort, an open-label Dose Selection Cohort (Part 1), followed by a double-blind, randomized, Placebo-Controlled Cohort (Part 2), and an optional Open-Label Extension (OLE) Cohort (Part 3)Read full original descriptionShow less

A Phase 2 Study of the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Epetraborole Tablets for the Treatment of Adults With Phlebotomy-Dependent Polycythemia Vera

This is a Phase 2 trial to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of oral epetraborole tablets for the treatment of adults with phlebotomy-dependent polycythemia vera (PV). The trial is designed to confirm the safety profile of oral epetraborole in the PV patient population and to identify 1 or more oral epetraborole doses for the treatment of phlebotomy-dependent PV. The study consists of an open-label Sentinel Cohort, an open-label Dose Selection Cohort (Part 1), followed by a double-blind, randomized, Placebo-Controlled Cohort (Part 2), and an optional Open-Label Extension (OLE) Cohort (Part 3)

Inclusion: Willing and able to read and provide written informed consent prior to the performance of any trial-specific procedures and willing to follow the protocol requirements; Aged 18 to 75 years (inclusive) at Screening; A confirmed diagnosis of PV according to ICC (Thiele, 2023), including Hgb/Hct level, EPO level, and JAK2 mutation status assessed by analysis of peripheral blood sampling; Documented positive JAK2 V617F (exon 14) or JAK2 exon 12 mutation; Hct <45% at Screening; Has records of all phlebotomies performed for at least 28 weeks (preferably up to 52 weeks) prior to Day 1; Phlebotomy-dependent, defined as at least 3 phlebotomies during the 28 weeks prior to Day 1, including a phlebotomy within 8 weeks prior to Screening; Either receiving OR not receiving cytoreductive therapy for PV, as follows:; Participants who are not currently receiving cytoreductive therapy must have either never received it or been discontinued from it for at least 24 weeks prior to Day 1 and any AEs due to cytoreductive therapy have either recovered or are ≤ Grade 1 prior to Day 1; Participants currently receiving cytoreductive therapy with HU, interferon, or busulfan must have received such therapy for at least 24 weeks prior to Day 1 and have been on a stable or decreasing dose for at least 8 weeks prior to Day 1, and with no planned change in dose during the trial; ECOG score of 0, 1, or 2; If FOCP; Must not be currently breastfeeding; If sexually active with a male partner: Must be either sexually abstinent or agree to use at least 2 medically accepted, effective methods of birth control from Screening through at least 1 week after the last dose of trial intervention; Must have a negative urine pregnancy test at Screening and on Day 1; the Day 1 urine test will be confirmed by a serum pregnancy test; Male participants who are sexually active with an FOCP must agree to use an effective barrier method of contraception from Screening through at least 1 week after the last dose of trial intervention; Agrees to not donate sperm (males) or ova (females) from Screening through at least 1 week after the last dose of trial intervention.

Exclusion: History of clinically significant arterial or venous thrombosis (eg, deep vein thrombosis or splenic vein thrombosis) within 24 weeks prior to Day 1; History of major bleeding events and/or a requirement for blood transfusion therapy due to bleeding in the 6 months prior to Day 1; Prior, concomitant, or planned therapy with ruxolitinib; Received any investigational drug within 6 weeks prior to Day 1 or 5 half-lives (whichever is longer) prior to Day 1 or has not recovered from adverse effects of prior administration of any investigational agent; Prior exposure to epetraborole; drug intolerance or hypersensitivity to any compound from the same class as epetraborole; History of prior drug-induced pneumonitis; Current skin malignancy or history of clinically significant skin cancer within 5 years prior to Day 1; Any major surgical procedure requiring general anesthesia within 1 month prior to Day 1 or planned elective surgery during the trial; Prior or concomitant therapy within 4 weeks prior to Day 1, or expected during the trial, with the following:; Drugs known to consistently produce myelosuppression: oxazolidinone antibiotics , chloramphenicol, mTORC inhibitors; Drugs that can inhibit ADH: some H2-receptor antagonists (eg, cimetidine, famotidine, ranitidine), pyrazoles (fomepizole); Drugs that inhibit ALDH: disulfiram, isoniazid, ketoconazole, certain cephalosporins , first-generation sulfonylureas; Severe hepatic impairment at Screening as evidenced by clinical signs of cirrhosis or end-stage hepatic disease; Known primary or secondary immunodeficiency defined as the following:; Primary immunodeficiency: rare, inherited genetic disorders, leading to frequent, severe, or unusual infections, autoimmune issues, and a higher cancer risk; Secondary immunodeficiency: acquired deficiencies, including those from chemotherapy/immunosuppressive drugs, certain cancers (like leukemia/lymphoma), severe malnutrition, major burns/trauma, and other chronic conditions. These are common and result from environmental influences or diseases, unlike primary ones that are genetic; Platelets >1000 × 109/L, WBC count >25 × 109/L; or presence of any blast cells in peripheral blood at Screening; Liver disease or liver injury at Screening as evidenced by:; ALT or AST >3 × ULN; Total bilirubin >2 × ULN; eGFR <30 mL/min/1.73 m2 at Screening; Known history of:; Hepatitis B or C infection; HIV infection plus either an active AIDS-defining illness or a known CD4 count <200/mm3 within 12 months prior to Day 1; Any other condition, prior therapy, or clinically significant co-morbidity at Screening that would, in the Investigator's opinion, interfere with the participant's ability to participate in the entire trial, pose a risk to the participant, or constitute a potentially confounding medical condition, including the following:; Uncontrolled hypertension >160/100 mmHg; Uncontrolled diabetes mellitus (HbA1c level of ≥9%); NYHA Class III/IV heart failure; Severe coronary artery disease, including unstable angina or myocardial infarction in the 12 months prior to Screening, or likely to require invasive procedure(s) to manage their CAD during the trial; Symptomatic CVD or recent stroke within 12 months prior to Screening or active CVD with symptomatic transient events; Non-cutaneous malignancy requiring treatment; Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (Tefferi, 2023); Diagnosis of secondary polycythemia.

ClinicalTrials.gov NCT07891533