A Study of IMR-687 in Subjects With Beta Thalassemia
Condition: β Thalassemia
MeSH terms: Thalassemia; beta-Thalassemia
Intervention: IMR-687; Placebo
Intervention description: Oral administration of once daily IMR-687; Oral administration of once daily Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: Double-Blind
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Transfusion; TDT; NTDT

Summary:

      A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
    

Eligibility criteria:

        Inclusion Criteria:

          1. Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history.
             Concomitant alpha gene deletion, duplication, or triplication is allowed.

          2. Documentation of the dates of transfusion events and the number of all pRBC units per
             event within the 12 weeks prior to the Baseline (Day 1) visit. .

          3. Must be willing and able to complete all study assessments and procedures, and to
             communicate effectively with the investigator and site staff.

          4. TDT Subjects: subjects must be regularly transfused, defined as >3 to 10 pRBC units in
             the12 weeks prior to Baseline (Day 1) visit and no transfusion-free period for >35
             days during that period.

          5. NTDT subjects: Subjects must be transfusion independent, defined as 0 to ≤3 units of
             pRBCs received during the 12-week period prior to the Baseline (Day 1) visit, must not
             be on a regular transfusion program, must be RBC transfusion-free for at least ≥ 4
             weeks prior to randomization, and must not be scheduled to start a regular

          6. hematopoietic stem cell transplantation within 9 months.

          7. NTDT subjects: Subjects must have Hb ≤10.0 g/dL at Screening; the screening Hb sample
             must be collected 7 to 28 days prior to randomization. Hb values within 21 days
             post-transfusion will be excluded.

          8. ECOG performance score of 0 to 1

          9. Female subjects must not be pregnant, or breastfeeding and be highly unlikely to
             become pregnant. Male subjects must be unlikely to impregnate a partner.

        Exclusion Criteria:

          1. Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β
             thalassemia.

          2. Body mass index (BMI) <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2

          3. Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or
             acute event of malaria, or who are known to be positive for human immunodeficiency
             virus (HIV).

          4. Stroke requiring medical intervention ≤24 weeks prior to randomization.

          5. Platelet count >1000 × 109/L.

          6. Participated in another clinical study of an investigational agent (or device) within
             30 days or 5-half-lives of date of informed consent, whichever is longer, or is
             currently participating in another study.

          7. For Subjects on iron chelation therapy (ICT) at the time of ICF signing, initiation of
             ICT less than 24 weeks before the predicted randomization date.

          8. Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6
             months prior to randomization (Day 1).

          9. Subjects who have major organ damage