Back to resultsA Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects With Sickle Cell Disease
Primary Purpose
Sickle Cell Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
INCB059872
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle cell disease (SCD), sickle cell SS, lysine demethylase 1 (LSD1) inhibition
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.
Sites / Locations
- Acevedo Clinical Research Associates
- Advanced Pharma
- Vita Health and Medical Center
- University of Illinois at Chicago
- Boston University
- Virginia Commonwealth University
- Blood Centers of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
INCB059872 0.5 mg
INCB059872 1 mg
INCB059872 2 mg
Arm Description
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 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 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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Cmax of INCB059872
Defined as maximum observed plasma concentration.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03132324
Brief Title
A Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects 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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Why Stopped
This study is terminated due to a business decision not to pursue INCB059782 in Sickle Cell Disease indication.
Study Start Date
April 20, 2017 (Actual)
Primary Completion Date
October 3, 2018 (Actual)
Study Completion Date
October 3, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Sickle cell disease (SCD), sickle cell SS, lysine demethylase 1 (LSD1) inhibition
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
INCB059872 0.5 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
INCB059872 1 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
INCB059872 2 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
INCB059872
Intervention Description
INCB059872 tablets
Primary Outcome Measure Information:
Title
Safety and tolerability of INCB059872 assessed by monitoring frequency, duration, and severity of adverse events
Description
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.
Time Frame
Screening through 35 days after end of treatment, up to approximately 3 months per participant.
Title
Change in fetal hemoglobin (HbF) from baseline
Description
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.
Time Frame
Baseline through 2 weeks after end of treatment, up to approximately 2.5 months per participant.
Secondary Outcome Measure Information:
Title
Cmax of INCB059872
Description
Defined as maximum observed plasma concentration.
Time Frame
Baseline to Day 28.
Title
AUC0-t of INCB059872
Description
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.
Time Frame
Baseline to Day 28.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fitzroy Dawkins, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Acevedo Clinical Research Associates
City
Miami
State/Province
Florida
ZIP/Postal Code
33142
Country
United States
Facility Name
Advanced Pharma
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Facility Name
Vita Health and Medical Center
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60607
Country
United States
Facility Name
Boston University
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Blood Centers of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects With Sickle Cell Disease
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