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

Study Overview
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Brief Summary
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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.

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

Conditions
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Sickle Cell Disease, Sickle Cell Anemia, Sickle Cell Disorders, Hemoglobin S Disease, Sickling Disorder Due to Hemoglobin S

Intervention / Treatment
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* Drug: HQK-1001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HQK-1001 (30 mg/kg)<br> | Drug: HQK-1001<br>* HQK-1001 tablets, once daily for daily 26 weeks<br>|
| Experimental: HQK-1001 (40 mg/kg)<br> | Drug: HQK-1001<br>* HQK-1001 tablets, once daily for daily 26 weeks<br>|
| Experimental: HQK-1001 (50 mg/kg)<br> | Drug: HQK-1001<br>* HQK-1001 tablets, once daily for daily 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Physical exams, vital signs, clinical laboratory safety assessments, ECG and adverse event monitoring. | Day 1 through Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal hemoglobin levels |  | Day 1 and Weeks 4, 8, 12, 16, 20, 25, 26 and 30 | 
| Incidence of sickle cell crisis events |  | Day 1 through Week 30 |