Hemoglobin S Disease, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S
Conditions
Brief summary
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.
Interventions
DRUGHQK-1001
HQK-1001 tablets, once daily for daily 26 weeks
Sponsors
HemaQuest Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | Day 1 through Week 30 | Physical exams, vital signs, clinical laboratory safety assessments, ECG and adverse event monitoring. |
Secondary
| Measure | 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 |
Countries
Canada, Egypt, Jamaica, Lebanon, United States
Outcome results
None listed