Back to resultsA Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Primary Purpose
Autoimmune Hemolytic Anemia
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Parsaclisib
Sponsored by
About this trial
This is an interventional treatment trial for Autoimmune Hemolytic Anemia focused on measuring autoimmune hemolytic anemia, phosphatidylinositol 3-kinase (PI3K) inhibitor
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of AIHA based on the presence of hemolytic anemia and serological evidence of anti-erythrocyte antibodies, detectable by the direct antiglobulin test.
- Participants who have disease progression after treatment with standard therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
- Hemoglobin 7 to 10 g/dL.
- No evidence of a lymphoproliferative malignancy or other autoimmune-related underlying conditions.
- Eastern Cooperative Oncology Group performance status of 0 to 2.
- Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
- Pregnant or breastfeeding women.
- Concurrent conditions and history of other protocol-specified diseases.
- ANC < 1.5 × 10^9/L.
- Platelet count < 100 × 10^9/L.
- Severely impaired liver function.
- Impaired renal function with estimated creatinine clearance less than 45 mL/min.
- Anti-phospholipid antibodies positive or elevated anti-streptolysin antibodies.
- Positive serology test results for hepatitis B surface antigen or core antibody, or hepatitis C virus antibody with detectable RNA at screening, consistent with active or chronic infection.
- Known HIV infection or positivity on immunoassay.
- History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
- Known hypersensitivity or severe reaction to parsaclisib or its excipients.
Sites / Locations
- Georgetown University Hospital
- University of Minnesota
- Washington University School of Medicine
- Montefiore Medical Center
- Weill Medical College of Cornell University
- University Health System Inc., Dba the University of Tn Medical Center
- Allgemeines Krankenhaus Der Stadt Wien
- Centre Hospitalier Universitaire Henri Mondor
- Centre Hospitalier Regional Universitaire (Chru) de Lille
- Fondazione Irccs Ca Granda Ospedale Maggiore
- UNIVERSIT� DI NAPOLI FEDERICO II
- AZIENDA OSPEDALIERO UNIVERSITARIA MAGGIORE DELLA CARIT� DI NOVARA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Parsaclisib 1 mg QD
Parsaclisib 2.5 mg QD
Arm Description
Parsaclisib at 1 milligram (mg) once daily (QD) for 12 weeks followed by extension period, with a dose-increase option (to 2.5 mg QD) at Week 6 for participants who fulfill dose increase criteria.
Parsaclisib at 2.5 mg QD for 12 weeks followed by extension period.
Outcomes
Primary Outcome Measures
Percentage of Participants Attaining a Complete Response at Any Visit From Week 6 to Week 12
A complete response was defined as hemoglobin >12 grams per deciliter (g/dL) not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Percentage of Participants Attaining a Partial Response at Any Visit From Week 6 to Week 12
A partial response was defined as hemoglobin 10-12 g/dL or at least a 2 g/dL increase from Baseline not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Treatment Period
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy, or required changes in the study drug. Anemia and transfusions should not have been reported as AEs unless they represented a clinically meaningful decrease from Baseline in hemoglobin. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Secondary Outcome Measures
Number of Participants With Any TEAE in the Extension Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy, or required changes in the study drug. Anemia and transfusions should not have been reported as AEs unless they represented a clinically meaningful decrease from Baseline in hemoglobin. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Percentage of Participants Attaining a Complete Response During Post-Baseline Visits
A complete response was defined as hemoglobin >12 g/dL) not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Percentage of Participants Attaining a Partial Response During Post-Baseline Visits
A partial response was defined as hemoglobin 10-12 g/dL or at least a 2 g/dL increase from Baseline not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Percentage of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From Baseline
Hemoglobin levels were assessed throughout the study.
Change From Baseline in Hemoglobin
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Percentage Change From Baseline in Hemoglobin
Percentage change from Baseline was calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) x 100.
Percentage of Participants Requiring Transfusions
A participant was defined to have required a transfusion if his or her last transfusion was within 7 days of the visit date.
Percentage of Participants Who Achieved Normalization of Hemoglobin, Haptoglobin, Lactate Dehydrogenase (LDH), Reticulocyte Count, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Normalization was determined by the Investigator based on normal ranges for the clinical reference laboratory.
Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease)
Prednisone use was monitored throughout the study.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale Scores
The FACIT-F subscale is a 13-item instrument designed to assess fatigue/tiredness and its impact on daily activities and functioning in a number of chronic diseases. Participants were asked to respond to 13 statements that people with the illness have said are important on the following scale: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. Participants were asked to indicate the response as it applied to the last 7 days. The total fatigue subscale score ranges from 0 to 52; a higher score indicates more severe impact on daily activities and functioning.
Mean Cmax of Parsaclisib
Cmax was defined as the maximum observed concentration. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean Tmax of Parsaclisib
tmax was defined as the time to the maximum concentration. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean Cmin of Parsaclisib
Cmin was defined as the minimum observed concentration over the dose interval. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean AUC0-4 of Parsaclisib
AUC0-4 was defined as the area under the concentration-time curve from time = 0 to 4 hours postdose. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean AUC0-t of Parsaclisib
AUC0-t was defined as the area under the concentration-time curve from time = 0 to the last measureable concentration at time = t. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean Clast of Parsaclisib
Clast was defined as the last measurable concentration (above the quantification limit). Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Mean Tlast of Parsaclisib
Tlast was defined as the time of the last measurable concentration (above the quantification limit). Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Change From Baseline in Reticulocyte Count
Change from Baseline was calculated as the post-Baseline value minus the Baseline value
Change From Baseline in Direct Antiglobulin Test (DAT) for Immunoglobulin G (IgG) and C3b
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Cold Agglutinin Levels
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Haptoglobin, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in LDH
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in CH50
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in C3 and C4
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03538041
Brief Title
A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Official Title
A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 21, 2018 (Actual)
Primary Completion Date
August 5, 2021 (Actual)
Study Completion Date
September 8, 2023 (Anticipated)
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 is to evaluate the safety and efficacy of parsaclisib administered orally to participants with autoimmune hemolytic anemia (AIHA) who have decreased hemoglobin and evidence of ongoing hemolysis that requires treatment intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Hemolytic Anemia
Keywords
autoimmune hemolytic anemia, phosphatidylinositol 3-kinase (PI3K) inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Parsaclisib 1 mg QD
Arm Type
Experimental
Arm Description
Parsaclisib at 1 milligram (mg) once daily (QD) for 12 weeks followed by extension period, with a dose-increase option (to 2.5 mg QD) at Week 6 for participants who fulfill dose increase criteria.
Arm Title
Parsaclisib 2.5 mg QD
Arm Type
Experimental
Arm Description
Parsaclisib at 2.5 mg QD for 12 weeks followed by extension period.
Intervention Type
Drug
Intervention Name(s)
Parsaclisib
Other Intervention Name(s)
INCB050465
Intervention Description
Parsaclisib administered orally.
Primary Outcome Measure Information:
Title
Percentage of Participants Attaining a Complete Response at Any Visit From Week 6 to Week 12
Description
A complete response was defined as hemoglobin >12 grams per deciliter (g/dL) not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Time Frame
Week 6 to Week 12
Title
Percentage of Participants Attaining a Partial Response at Any Visit From Week 6 to Week 12
Description
A partial response was defined as hemoglobin 10-12 g/dL or at least a 2 g/dL increase from Baseline not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Time Frame
Week 6 to Week 12
Title
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Treatment Period
Description
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy, or required changes in the study drug. Anemia and transfusions should not have been reported as AEs unless they represented a clinically meaningful decrease from Baseline in hemoglobin. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time Frame
up to a maximum of 99 days
Secondary Outcome Measure Information:
Title
Number of Participants With Any TEAE in the Extension Period
Description
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy, or required changes in the study drug. Anemia and transfusions should not have been reported as AEs unless they represented a clinically meaningful decrease from Baseline in hemoglobin. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time Frame
up to approximately 3 years
Title
Percentage of Participants Attaining a Complete Response During Post-Baseline Visits
Description
A complete response was defined as hemoglobin >12 g/dL) not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Time Frame
up to approximately 2.5 years
Title
Percentage of Participants Attaining a Partial Response During Post-Baseline Visits
Description
A partial response was defined as hemoglobin 10-12 g/dL or at least a 2 g/dL increase from Baseline not attributed to a transfusion effect and the normalization of hemolytic markers. No transfusion effect was defined as > 1 week since the last transfusion.
Time Frame
up to approximately 2.5 years
Title
Percentage of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From Baseline
Description
Hemoglobin levels were assessed throughout the study.
Time Frame
up to approximately 2.5 years
Title
Change From Baseline in Hemoglobin
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Percentage Change From Baseline in Hemoglobin
Description
Percentage change from Baseline was calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) x 100.
Time Frame
Baseline; up to approximately 2.5 years
Title
Percentage of Participants Requiring Transfusions
Description
A participant was defined to have required a transfusion if his or her last transfusion was within 7 days of the visit date.
Time Frame
Baseline; up to approximately 2.5 years
Title
Percentage of Participants Who Achieved Normalization of Hemoglobin, Haptoglobin, Lactate Dehydrogenase (LDH), Reticulocyte Count, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Description
Normalization was determined by the Investigator based on normal ranges for the clinical reference laboratory.
Time Frame
up to approximately 2.5 years
Title
Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease)
Description
Prednisone use was monitored throughout the study.
Time Frame
up to approximately 2.5 years
Title
Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale Scores
Description
The FACIT-F subscale is a 13-item instrument designed to assess fatigue/tiredness and its impact on daily activities and functioning in a number of chronic diseases. Participants were asked to respond to 13 statements that people with the illness have said are important on the following scale: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. Participants were asked to indicate the response as it applied to the last 7 days. The total fatigue subscale score ranges from 0 to 52; a higher score indicates more severe impact on daily activities and functioning.
Time Frame
Baseline; up to approximately 2.5 years
Title
Mean Cmax of Parsaclisib
Description
Cmax was defined as the maximum observed concentration. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean Tmax of Parsaclisib
Description
tmax was defined as the time to the maximum concentration. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean Cmin of Parsaclisib
Description
Cmin was defined as the minimum observed concentration over the dose interval. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean AUC0-4 of Parsaclisib
Description
AUC0-4 was defined as the area under the concentration-time curve from time = 0 to 4 hours postdose. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean AUC0-t of Parsaclisib
Description
AUC0-t was defined as the area under the concentration-time curve from time = 0 to the last measureable concentration at time = t. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean Clast of Parsaclisib
Description
Clast was defined as the last measurable concentration (above the quantification limit). Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Mean Tlast of Parsaclisib
Description
Tlast was defined as the time of the last measurable concentration (above the quantification limit). Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.
Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Title
Change From Baseline in Reticulocyte Count
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in Direct Antiglobulin Test (DAT) for Immunoglobulin G (IgG) and C3b
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in Cold Agglutinin Levels
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in Haptoglobin, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in LDH
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in CH50
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
Title
Change From Baseline in C3 and C4
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; up to approximately 2.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of AIHA based on the presence of hemolytic anemia and serological evidence of anti-erythrocyte antibodies, detectable by the direct antiglobulin test.
Participants who have disease progression after treatment with standard therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
Hemoglobin 7 to 10 g/dL.
No evidence of a lymphoproliferative malignancy or other autoimmune-related underlying conditions.
Eastern Cooperative Oncology Group performance status of 0 to 2.
Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
Pregnant or breastfeeding women.
Concurrent conditions and history of other protocol-specified diseases.
ANC < 1.5 × 10^9/L.
Platelet count < 100 × 10^9/L.
Severely impaired liver function.
Impaired renal function with estimated creatinine clearance less than 45 mL/min.
Anti-phospholipid antibodies positive or elevated anti-streptolysin antibodies.
Positive serology test results for hepatitis B surface antigen or core antibody, or hepatitis C virus antibody with detectable RNA at screening, consistent with active or chronic infection.
Known HIV infection or positivity on immunoassay.
History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
Known hypersensitivity or severe reaction to parsaclisib or its excipients.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen Butler, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University Health System Inc., Dba the University of Tn Medical Center
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Allgemeines Krankenhaus Der Stadt Wien
City
Vienna
ZIP/Postal Code
01090
Country
Austria
Facility Name
Centre Hospitalier Universitaire Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Centre Hospitalier Regional Universitaire (Chru) de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Fondazione Irccs Ca Granda Ospedale Maggiore
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
UNIVERSIT� DI NAPOLI FEDERICO II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
AZIENDA OSPEDALIERO UNIVERSITARIA MAGGIORE DELLA CARIT� DI NOVARA
City
Novara
ZIP/Postal Code
28100
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
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