| Eligibility |
Inclusion Criteria:
- Written informed parental/guardian consent and participant assent/consent has been
obtained per institutional review board (IRB)/Ethics Committee (EC) policy and
requirements, consistent with International Conference on Harmonization (ICH)
guidelines
- Stated willingness to comply with all study procedures and availability for the
duration of the study
- Male or female participants, ages 4 to 30 years, inclusive
- Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta^0 thalassemia (HbS/ß^0 thal)
- Hemoglobin (Hb) =10.5 g/dL at baseline
- Concomitant hydroxyurea (HU) therapy is allowed if the dose has been stable for at
least 3 months with no anticipated need for dose adjustments during the study and no
sign of hematological toxicity
- Ability to take oral medication and willingness to adhere to daily voxelotor and
scheduled DCS/NIRS assessments
- If sexually active and female, must agree to abstain from sexual intercourse or to use
a highly effective method of contraception throughout the study period and for 30 days
after discontinuation of study drug. If sexually active and male, must agree to
abstain from sexual intercourse or willing to use barrier methods of contraception
throughout the study period and for 30 days after discontinuation of study drug.
- Females of child-bearing potential, i.e., who have begun menstruation and are sexually
active, are required to have a negative pregnancy test at screening before the initial
administration of study drug.
Exclusion Criteria:
- Any one of the following requiring medical attention within 14 days prior to signing
the informed consent form (ICF):
- Vaso-occlusive crisis (VOC)
- Acute chest syndrome (ACS)
- Splenic sequestration crisis
- Dactylitis
- Requires chronic transfusion therapy
- Red blood cell (RBC) transfusion within 60 days of signing the ICF
- Renal dysfunction requiring chronic dialysis or creatinine =1.5 mg/dL
- Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4× upper limit of
normal (ULN) for age
- Clinically relevant cardiac abnormality, in the opinion of the Investigator, such as:
- Hemodynamically significant heart disease, e.g., congenital heart defect,
uncompensated heart failure, or any unstable cardiac condition
- An arrhythmic heart condition requiring medical therapy
- Corrected QT interval by Fridericia (QTcF) >450 msec, congenital long QT syndrome,
second- or third-degree heart block at rest (with the exception of asymptomatic Mobitz
type I second degree heart block)
- Received an investigational drug within 30 days or 5 half-lives, whichever is longer,
of signing the ICF
- Heavy smoker (defined as smoking more than 10 cigarettes/day or its nicotine
equivalent including e-cigarettes)
- Unlikely to comply with the study procedures
- Other medical, psychological, or addictive condition that, in the opinion of the
Investigator, would confound or interfere with evaluation of safety and/or
pharmacokinetics (PK) of the investigational drug, prevent compliance with the study
protocol, or preclude informed consent
- Any condition affecting drug absorption, such as major surgery involving the stomach
or small intestine (prior cholecystectomy is acceptable)
- History of malignancy within the past 2 years prior to treatment Day 1 requiring
chemotherapy and/or radiation (with the exception of local therapy for non-melanoma
skin malignancy)
- Clinically significant bacterial, fungal, parasitic, or viral infection currently
receiving or that will require therapy
- Participants with acute bacterial infection requiring antibiotic use should delay
screening until the course of antibiotic therapy has been completed and the
infection has resolved, in the opinion of the investigator
- Known active hepatitis A, B, or C infection or human immunodeficiency virus
(HIV)-positive; known active
- Known active malaria
- Pregnant patients
- Evidence of abnormal high blood flow velocities on transcranial doppler (TCD) of 200
cm/sec or more
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