Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 Administered Daily in Patients With Sickle Cell Disease

A Randomized, Blinded, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 in Subjects With Sickle Cell Disease

The purpose of this study is to assess the safety and tolerability of HQK-1001 administered for a total of 12 weeks (with one dosing break) in subjects with sickle cell disease.

Inclusion Criteria:

• Diagnosis of SCD or sickle beta thalassemia (excluding Hemoglobin C)
• Between 12 and 60 years of age, inclusive
• At least one episode of a SCD-related crisis or complication (e.g., vaso-occlusive crisis, acute chest syndrome, priapism) per year for an average of 3 years or one episode of acute chest syndrome over the prior 5 years
• Screening (untransfused) HbF level >/= 2% as analyzed by a central laboratory
• If receiving hydroxyurea therapy, must be receiving a stable dose for at least 6 months
• Able and willing to give informed consent
• If female, must have a negative serum pregnancy test within 7 days of dosing
• If female, must not be of childbearing potential defined as post-menopausal by at least 2 years or surgically sterile, or must agree to use a medically accepted form of contraception throughout the study
• If the sexual partner of a male subject is a WCBP, she must agree to use a medically accepted form of birth control for themselves or their partner throughout the study
• In the view of the Investigator, able to comply with necessary study procedures

Exclusion Criteria:

• Red blood cell (RBC) transfusion within 3 months prior to beginning study medication
• Participation in a regular blood transfusion program
• More than 4 hospitalizations for acute sickle cell-related events in the previous 12 months
• An acute vaso-occlusive event within 3 weeks prior to receiving first dose of study medication
• Pulmonary hypertension requiring oxygen
• QTc > 450 msec on screening
• Alanine transaminase (ALT) > 3X upper limit of normal (ULN)
• Creatinine phosphokinase (CPK) > 20% above the ULN
• Serum creatinine >1.2 mg/dL
• An acute illness (e.g., febrile, gastrointestinal [GI], respiratory) within 72 hours prior to receiving first dose of study medication
• History of syncope, clinically significant dysrhythmias or resuscitation from sudden death
• Chronic opiate use which, in the view of the Investigator, could confound evaluation of an investigational drug
• Current abuse of alcohol or drugs
• Received another investigational agent within 4 weeks, or 5 half-lives, whichever is longer, prior to administration of study medication
• Currently pregnant or breast feeding a child
• Known infection with HIV-1
• Infection with hepatitis B or hepatitis C such that patients are currently on therapy or will be placed on therapy during the trial