Phase 1/2 Study of HQK-1001 in Patients With Beta Thalassemia

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 HQK-1001 administered daily for 8 weeks in subjects with beta thalassemia intermedia

Official Title
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A Multi-National, Blinded, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HQK-1001 in Subjects With Beta Thalassemia Intermedia, Including Hemoglobin E Beta Thalassemia

Conditions
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Beta Thalassemia

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: Clinical diagnosis of beta thalassemia intermedia or hemoglobin E beta thalassemia Average of the initial two hemoglobin levels of less than 10 g/dL within ≥ 30 days prior to randomization. Age ≥ 12 and ≤ 60 years Able and willing to give informed consent or assent (if less than 18 years of age) and comply with all study procedures If female and of childbearing potential, must have a documented negative pregnancy test at Day -1 and must agree to use one or more locally medically accepted methods of contraception in the month prior to randomization, through the entire study, and for 4 weeks after the last dosing of study medication Exclusion Criteria: Spleen palpable ≥ 2 cm below the left costal margin Pulmonary hypertension requiring oxygen therapy QTc > 450 msec on screening ECG Infection with hepatitis C, hepatitis B requiring therapy Known infection with HIV Red blood cell (RBC) transfusions within 2 months prior to administration of study medication with stable hemoglobin levels Fever greater than 38.5°C in the week prior to administration of study medication ALT > 4x upper limit of normal (ULN) Baseline elevation of CPK value prior to randomization Treatment with hydroxyurea within 2 months prior to administration of study medication Cancer diagnosis within 5 years of randomization (except for non-melanoma cutaneous malignancies) Serum creatinine > 1.5 mg/dl Received investigational systemic therapy within 30 days prior to randomization Currently pregnant or breast feeding a child Subject history of clinically significant arrhythmias or syncope Known current drug or alcohol abuse

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Matching placebo capsules administered once a day, orally, for 56 days<br>|
| Experimental: HQK-1001<br>HQK-1001 | Drug: HQK-1001<br>* HQK-1001 capsules (10, 20, 30 or 40 mg) administered once a day, orally, for 56 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 (4) physical exam |  | 168 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics assessed by plasma drug concentration levels |  | 140 days | 
| Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin |  | 168 days |