A Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects With Sickle Cell Disease

Study Overview
=================
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.

Official Title
-----------------
A Phase 1 Open-Label, Dose-Escalation Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects With Sickle Cell Disease

Conditions
-----------------
Sickle Cell Disease

Intervention / Treatment
-----------------
* Drug: INCB059872


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB059872 0.5 mg<br>INCB059872 0.5 mg tablet administered orally every other day (QOD) for 28 days on an empty stomach. If dose was well tolerated, once daily (QD) administration was evaluated independently and in parallel with QOD administration. | Drug: INCB059872<br>* INCB059872 tablets<br>|
| Experimental: INCB059872 1 mg<br>INCB059872 1 mg tablet administered orally QOD for 28 days on an empty stomach. If dose was well tolerated, QD administration was evaluated independently and in parallel with QOD administration. | Drug: INCB059872<br>* INCB059872 tablets<br>|
| Experimental: INCB059872 2 mg<br>INCB059872 2 mg tablet administered orally QOD for 28 days on an empty stomach. If dose was well tolerated, QD administration was evaluated independently and in parallel with QOD administration. | Drug: INCB059872<br>* INCB059872 tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of INCB059872 assessed by monitoring frequency, duration, and severity of adverse events | 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. | Screening through 35 days after end of treatment, up to approximately 3 months per participant. | 
| Change in fetal hemoglobin (HbF) from baseline | 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. | Baseline through 2 weeks after end of treatment, up to approximately 2.5 months per participant. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of INCB059872 | Defined as maximum observed plasma concentration. | Baseline to Day 28. | 
| AUC0-t of INCB059872 | Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration. | Baseline to Day 28. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sickle cell disease (SCD), sickle cell SS, lysine demethylase 1 (LSD1) inhibition