Actigraphy Improvement With Voxelotor (ActIVe) Study
Condition: Sickle Cell Disease; Sickle Cell Anemia
MeSH terms: Anemia, Sickle Cell
Intervention: Voxelotor
Intervention description: 500 mg Tablet, Oral, With or Without Food
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 12 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This is a study to evaluate the effect of voxelotor on daily physical activity and sleep
      quality, as measured by a wrist-worn device in participants with sickle cell disease (SCD)
      and chronic moderate anemia.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female participants with SCA (sickle hemoglobin with two sickle cell genes
             [HbSS] or sickle hemoglobin (S) and one beta thalassemia gene [HbS β0] thal genotype)

          2. Between 12 to 55 years of age (inclusive)

          3. Screening Hb level ≤8.0 g/dL

          4. Treatment with hydroxyurea (HU) therapy on study is permitted if the participant has
             been on a stable dose for at least 90 days before enrollment with no dose
             modifications planned or anticipated by the Investigator

          5. Treatment with glutamine is permitted

          6. Treatment with erythropoiesis-stimulating agents (ESAs) is permitted if the
             participant has been on a stable dose for at least 12 weeks before enrollment with no
             dose modifications planned or anticipated by the Investigator

          7. Female participants of child-bearing potential must use highly effective methods of
             contraception to 30 days after the last dose of study drug. Male participants must use
             barrier methods of contraception to 30 days after the last dose of study drug

          8. Females of child-bearing potential are required to have a negative pregnancy test
             before the administration of study drug

          9. Written informed consent and/or parental/guardian consent and participant assent per
             Institutional Review Board (IRB) policy and requirements, consistent with ICH
             guidelines

        Exclusion Criteria:

          1. Red blood cell (RBC transfusion within 3 months before initiation of study drug

          2. Planned initiation of regularly scheduled RBC transfusion therapy (also termed
             chronic, prophylactic, or preventive transfusion) during the study

          3. Hospitalization for vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within
             30 days prior to informed consent/assent.

          4. More than 10 VOCs requiring hospitalization, emergency department or clinic visit
             within the past 12 months

          5. Planned elective surgery within the next 6 months

          6. Physical inactivity attributable to clinically significant musculoskeletal,
             cardiovascular, or respiratory comorbidities

          7. Anemia due to bone marrow failure (eg, myelodysplasia)

          8. Absolute reticulocyte count (ARC) < 100 x10^9/L

          9. Screening alanine aminotransferase (ALT) > 4× upper limit of normal (ULN)

         10. Severe renal dysfunction (estimated glomerular filtration rate [GFR] < 30 mL/min/1.73
             m2 by Schwartz formula) or is on chronic dialysis

         11. Known active hepatitis A, B or C or known to be human immunodeficiency virus
             (HIV)-positive.

         12. Females who are breast-feeding or pregnant

         13. Major surgery within 8 weeks before enrollment. Participants must have completely
             recovered from any previous surgery before enrollment

         14. History of hematopoietic stem cell transplant or gene therapy

         15. Received an investigational drug within 30 days or 5-half-lives, whichever is longer,
             prior to consent, or is currently participating in another trial of an investigational
             or marketed drug (or medical device)

         16. Use of concomitant medications (eg, crizanlizumab) that confound the ability to
             interpret data from the study

         17. Medical, psychological, or behavioral condition that, in the opinion of the
             Investigator, would confound or interfere with evaluation of safety and/or efficacy of
             the study drug, prevent compliance with the study protocol; preclude informed consent;
             or, render the participant unable/unlikely to comply with the study procedures

         18. Use of herbal medications (e.g., St. John's Wort), sensitive cytochrome P450 (CYP) 3A4
             substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or
             moderate or strong CYP3A4 inducers

         19. Symptomatic coronavirus disease of 2019 (COVID-19) infection