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

Phase 1

Terminated

• Conditions: Sickle Cell Disease
• Interventions: Drug: INCB059872

• Registration Number: NCT03132324
• Lead Sponsor: Incyte Corporation

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-04-20
• Study First Submitted: 2017-04-24
• Study First Submitted QC: 2017-04-26
• Study First Posted: 2017-04-27
• Primary Completion: 2018-10-03
• Study Completion: 2018-10-03
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-24
• Last Update Posted: 2019-10-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INCB059872 0.5 mg	INCB059872	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.
INCB059872 1 mg	INCB059872	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.
INCB059872 2 mg	INCB059872	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.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (7)

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

Acevedo Clinical Research Associates; 🇺🇸 Miami, Florida, United States

Advanced Pharma; 🇺🇸 Miami, Florida, United States

Vita Health and Medical Center; 🇺🇸 Tamarac, Florida, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Blood Centers of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Boston University; 🇺🇸 Boston, Massachusetts, United States