A Study of IMR-687 in Subjects With Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
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: Triple (Participant, Care Provider, Investigator)
Masking description: Double-Blind
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Sickle Cell Disease

Summary:

      A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease
    

Eligibility criteria:

        Inclusion Criteria:

          1. Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)

          2. Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be
             excluded.

          3. Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in
             the past 12 months at the time of informed consent signing and at randomization (Day
             1).

          4. Subjects receiving HU must have received it continuously for at least 6 months prior
             to signing informed consent, and must have been on a stable dose for at least 3 months
             prior to signing the informed consent, with no anticipated need for dose adjustments
             during the study including the screening period, in the opinion of the investigator.

          5. Female subjects must not be pregnant or breastfeeding and be highly unlikely to become
             pregnant. Male subjects must be unlikely to impregnate a partner.

          6. Must be willing and able to complete all study assessments and procedures, and to
             communicate effectively with the investigator and site staff.

        Exclusion Criteria:

          1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4
             days prior to randomization (Day 1).

          2. Subjects participating in a chronic/prophylactic RBC transfusion program (i.e.,
             regularly scheduled RBC transfusions); any transfusions within 21 days of screening or
             baseline Hb measurements

          3. Subjects with HbF >25% at screening.

          4. Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine
             aminotransferase or aspartate aminotransferase >3x upper limit of normal.

          5. Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a BMI >35 kg/m2.

          6. 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).

          7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).

          8. Prior exposure to IMR-687.

          9. Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban,
             edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least
             28 days prior to randomization (Day 1).

         10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months
             prior to signing the informed consent.

         11. Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth
             factor treatment within 3 months of signing the ICF or anticipated need for such
             agents during the study.

         12. Prior gene therapy.