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 effects of HQK-1001 on Hb F in subjects with sickle cell disease.
Interventions
DRUGHQK-1001
HQK-1001 tablets, twice daily for 48 weeks
DRUGPlacebo
Placebo tablets, twice daily for 48 weeks
Sponsors
HemaQuest Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in % fetal hemoglobin | Day 1 through Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48 | 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. |
Countries
Canada, Egypt, Jamaica, Lebanon, United States
Outcome results
None listed