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

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: INCB059872

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Miami, Florida, United States, 33147
      • Advanced Pharma
    • Tamarac, Florida, United States, 33319
      • Vita Health and Medical center
  • Illinois
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston University
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Blood Centers of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INCB059872 0.5 mg; 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; INCB059872 tablets
Experimental: INCB059872 1 mg; 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; INCB059872 tablets
Experimental: INCB059872 2 mg; 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; INCB059872 tablets

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.

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Fitzroy Dawkins, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 28, 2019
• Last Update Submitted That Met QC Criteria: October 24, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Sickle cell disease (SCD); sickle cell SS; lysine demethylase 1 (LSD1) inhibition
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: INCB 59872-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No