Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD

Inclusion Criteria:

• Male or female with sickle cell disease
• Documentation of SCD genotype HbSS or HbSB0
• Age 18 to < 60 years, inclusive
• Participants, who if female and of child bearing potential, agree to use highly effective methods of contraception or practicing abstinence from study start to 30 days after the last dose of study drug, and who if male, agree to use barrier methods of contraception or practice abstinence from study start to 30 days after the last dose of study drug
• Participant has provided documented informed consent

Exclusion Criteria:

• More than 10 vaso-occlusive crises (VOCs) within 12 months of screening that required a hospital, emergency room, or clinic visit
• Female participant who is breast feeding or pregnant
• Hospitalized for sickle cell crisis or other vaso-occlusive event prior to 30 days of dosing (ie, a vaso-occlusive event cannot be within 30 days prior to dosing)
• Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
• Severe renal dysfunction or on chronic dialysis
• 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)
• History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
• 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
• Inadequate venous access as determined by the Investigator/site staff
• Ongoing or recent (within 2 years) substance abuse
• Inability to undergo magnetic resonance imaging (MRI) or cardiopulmonary exercise test (CPET) assessments (Cohort B only)
• Known allergy to voxelotor