The Effect of Voxelotor on Cerebral Perfusion and Oxygenation (ESR-C005)

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Documented severe SCD genotype (HbSS, HbS-β) which must be based on
previous or confirmed by high performance liquid chromatography (HPLC) testing
during screening.
2. Age 18 and above
3. Hemoglobin (Hb) <=10.5 g/dL
4. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be
stable for at
least 90 days prior to participation and with no anticipated need for dose
adjustments
5. Participants, who if female and of child bearing potential, are using
highly effective
methods of contraception from study start to 30 days after the last dose of
study drug, and who if male are willing to use barrier methods of
contraception, from study start to 30
days after the last dose of study drug.
6. Participant has provided documented informed consent or assent (the
informed consent
form [ICF] must be reviewed and signed by each participant; the participant*s
legal representative or legal guardian, and the participant*s assent must be
obtained).
7. For extension phase: clinical benefit being apparent, clinical benefit is
defined as an increase in Hb of > 0.62 mmol/L (1 g/dL) and or clinical response
assessed by the investigator or reported by patient (e.g. increased endurance,
diminished fatigue, improved well-being).

Exclusion Criteria

1. No informed consent has been given
2. Contra-indication for MRI or acetazolamide
3. Female who is breast feeding or pregnant.
4. Patients who are receiving regularly scheduled blood (RBC) transfusion
therapy (also
termed chronic, prophylactic, or preventive transfusion) or have received a RBC
transfusion for any reason within 90 days before participation.
5. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14
days prior participation.
6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 ×
ULN.
7. Participants with clinically significant bacterial, fungal, parasitic or
viral infection which
require therapy:
• Participants with acute bacterial infection requiring antibiotic use should
delay
screening/enrollment until the course of antibiotic therapy has been
completed.
• Participants with known active hepatitis A, B, or C or who are known to be
human immunodeficiency virus (HIV) positive.
8. Severe renal dysfunction (estimated glomerular filtration rate <30mL/min).
9. History of malignancy within the past 2 years prior to participation
requiring chemotherapy and/or radiation (with the exception of local therapy
for non-melanoma
skin malignancy).
10. History of unstable or deteriorating cardiac or pulmonary disease within 6
months prior
to consent including but not limited to the following:
• Unstable angina pectoris or myocardial infarction or elective coronary
intervention.
• Congestive heart failure requiring hospitalization.
• Uncontrolled clinically significant arrhythmias.
11. Any condition affecting drug absorption, such as major surgery involving
the stomach or
small intestine (prior cholecystectomy is acceptable).
12. Participated in another clinical trial of an investigational agent (or
medical device) within
30 days or 5 half-lives of date of informed consent, whichever is longer, or is
currently
participating in another trial of an investigational agent (or medical device)
13. Medical, psychological, or behavioral conditions, which, in the opinion of
the
Investigator, may preclude safe participation, confound study interpretation,
interfere
with compliance, or preclude informed consent.
14. Receipt of erythropoietin or other hematopoietic growth factors within 28
days of signing
ICF or anticipated need for such agents during the study.