Effects 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 effects of HQK-1001 on Hb F in subjects with sickle cell disease.

Official Title
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A Randomized, Placebo-controlled, Phase 2 Study of HQK-1001 in 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
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HQK-1001<br> | Drug: HQK-1001<br>* HQK-1001 tablets, twice daily for 48 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablets, twice daily for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in % fetal hemoglobin |  | Day 1 through Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and number of SCD pain crises and SCD-related complications |  | Day 1 through Week 52 | 
| Subject reported daily pain scale scores and analgesic use |  | 7 consecutive days following clinic visits at Day 1, and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | 
| Change in FACIT Fatigue Scale results |  | Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | 
| Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments |  | Day 1 through Week 52 | 
| HQK-1001 pharmacokinetic parameters | A subset of subjects (7) will undergo sampling for detailed analysis of pharmacokinetic parameters (AUC, Cmax) with samples taken pre-dose, and 1, 2, 4, 8, and 10 hours after the morning dose at Week 4. | 1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48 |