A Study of HQK-1001 in Patients With Sickle Cell Disease

A Randomized, Open-Label, Multi-Dose Study of HQK-1001 in Subjects With Sickle Cell Disease

The purpose of this study is to evaluate the safety and tolerability of three dose levels of HQK-1001 administered once daily for 26 weeks in subjects with sickle cell disease.

Inclusion Criteria:

• Established diagnosis of SCD
• Males and females between 12 and 60 years of age, inclusive
• At least 3 episodes of a SCD-related crisis or complication in the 3 years prior to screening OR 1 episode of acute chest syndrome in the 5 years prior to screening
• If receiving hydroxyurea, must be receiving a stable dose for at least 6 months prior to screening
• If hydroxyurea treatment has been discontinued, at least 3 months have elapsed since last dose
• If transfusion in the 4 months prior to screening, then HbA level < 20% at screening
• Average of the initial two HbF levels ≥ 2.0 % within ≤ 7 days prior to the initial dose of HQK-1001. The two must be obtained ≥ 24 hours apart
• Ability to swallow tablets
• Able and willing to give informed consent and assent (if applicable)
• If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 7 days of first dose of HQK-1001
• If a subject is a WCBP, she must agree to use an effective form of contraception within 7 days of the initial dose of HQK-1001 and for one month after HQK-1001 discontinuation
• Sexually active male subjects (with WCBP partners) must agree to use latex condoms or ensure that their partner(s) use an effective form of contraception
• In the view of the Investigator, subject is able and willing to comply with necessary study procedures

Exclusion Criteria:

• More than 4 hospitalizations for acute sickle cell related events in the previous 12 months prior to screening
• Pulmonary hypertension requiring oxygen therapy
• QTc > 450 msec (male) or 470 msec (female) on screening ECG (QT corrected by Fridericia's formula)
• Assigned to a regular transfusion program
• Use of erythropoiesis stimulating agents within 90 days of screening
• ALT > 3x upper limit of normal (ULN)
• Serum creatinine > 1.2 mg/dL
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• An acute vaso-occlusive event within 3 weeks prior to screening
• Creatine phosphokinase (CK) > 20% above the ULN
• An acute illness (e.g., febrile, GI, respiratory) within 72 hours prior to screening
• 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 screening
• 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