Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 Administered Daily 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 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.

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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: HQK-1001


Participation Criteria
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Eligibility Criteria
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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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br> | Drug: HQK-1001<br>* HQK-1001 capsules. 10 mg/kg, 20 mg/kg or 30 mg/kg administered once a day on dosing days.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo capsule. Administered orally once a day on dosing days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by (1) adverse events (2) laboratory values (3) vital signs, and (4) physical exam. |  | 126 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics assessed by plasma drug concentration levels. |  | Days 0, 6, 69 and 97 post first dose | 
| Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin. |  | Every 2 weeks through Day 126 post first dose |