Sickle Cell Disease
Conditions
Keywords
Sickle cell disease (SCD), sickle cell SS, lysine demethylase 1 (LSD1) inhibition
Brief summary
The purpose of this study was to evaluate the safety and tolerability, and the pharmacokinetic and biologic activity of INCB059872 in participants with sickle cell disease.
Interventions
DRUGINCB059872
INCB059872 tablets
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SCD (sickle cell SS) confirmed through hemoglobin electrophoresis. * Must be red blood cell (RBC) transfusion-independent (not currently on regularly scheduled transfusions) for ≥ 3 months from the time of first dose of study drug. * No RBC transfusion within 30 days of first dose of study drug. * Hydroxyurea (HU) refractory -Must not have received HU therapy during the 3 months before receiving study drug. * Creatinine clearance ≥ 60 mL/min based on the institutional formula. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Any unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities not expected to resolve. * Pregnant or nursing women or participants expecting to conceive or father children within the projected duration of the study, starting with screening visit through completion of safety follow-up. * Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) before receiving the first dose of study drug (requirement may be waived with medical monitor approval). * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. * Prior receipt of LSD1 inhibitor therapy for any indication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of INCB059872 assessed by monitoring frequency, duration, and severity of adverse events | Screening through 35 days after end of treatment, up to approximately 3 months per participant. | An adverse event is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. |
| Change in fetal hemoglobin (HbF) from baseline | Baseline through 2 weeks after end of treatment, up to approximately 2.5 months per participant. | Pharmacodynamic activity assessed by measuring changes of HbF from baseline and their correlation to INCB059872 treatment. The HbF (F cells) in human whole blood will be characterized using flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of INCB059872 | Baseline to Day 28. | Defined as maximum observed plasma concentration. |
| AUC0-t of INCB059872 | Baseline to Day 28. | Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration. |
Countries
United States
Outcome results
None listed