Effects of HQK-1001 in Patients With Sickle Cell Disease

A Randomized, Placebo-controlled, Phase 2 Study of HQK-1001 in Sickle Cell Disease

The purpose of this study is to evaluate the effects of HQK-1001 on Hb F in subjects with sickle cell disease.

Inclusion Criteria:

• Males and females between 12 and 60 years of age
• Diagnosis of SCD, type Hb SS or Hb S-B0 Thalassemia
• At least 1 episode of SCD pain crisis, acute chest syndrome, other acute SCD complications, or leg ulcers in the 12 months prior to screening
• Not being treated with Hydroxyurea (HU); if HU treatment has been previously administered and then discontinued, at least 3 months must have elapsed since last dose of HU
• If subject has been transfused in the 3 months prior to screening, then Hb A level < 20% at screening
• Baseline Hb F level obtained within 14 days prior to randomization
• Able to swallow tablets
• Able and willing to give informed consent and/or assent
• If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 14 days of first dose of HQK-1001 and a negative urine pregnancy test prior to dosing on Day 1
• If a subject is a WCBP, she must agree to use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation
• Sexually active male subjects who have not had a vasectomy must agree to use latex condoms with WCBP partners or ensure that their partner(s) use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation.

Exclusion Criteria:

• Assigned to a regular transfusion program
• Use of erythropoiesis stimulating agents within 90 days prior to screening
• An SCD pain crisis or SCD-related acute complication within 3 weeks prior to randomization
• More than 5 SCD pain crisis or SCD-related acute complications within 12 months prior to screening
• Pulmonary hypertension requiring therapy
• ALT or AST > 3x ULN
• Serum creatinine > 1.5x ULN
• Serum amylase levels > 1.5x ULN
• Serum lipase level > 1.5x ULN
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• 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 due to SCD-related complication
• Symptomatic peptic ulcer, hiatus hernia, or gastroesophageal reflux disease (GERD)
• History of pancreatitis
• Chronic opiate use, which, in the view of the investigator, could confound evaluation of an investigational drug
• Current abuse of alcohol or drugs
• Use of 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 subjects are currently on anti-viral therapy or will be placed on therapy