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.
Brief Title
A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Completion Date
Completion Date Type
Actual
Conditions
Autoimmune Hemolytic Anemia
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
autoimmune hemolytic anemia
phosphatidylinositol 3-kinase (PI3K) inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03538041
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 50465-206
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Primary Outcomes
Outcome 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.
Outcome Measure
Percentage of Participants Attaining a Complete Response at Any Visit From Week 6 to Week 12
Outcome Time Frame
Week 6 to Week 12
Outcome 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.
Outcome Measure
Percentage of Participants Attaining a Partial Response at Any Visit From Week 6 to Week 12
Outcome Time Frame
Week 6 to Week 12
Outcome 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.
Outcome Measure
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Outcome Time Frame
up to 1638 days
Secondary Ids
Secondary Id
Parsaclisib
Secondary Id
2017-003652-22
Secondary Outcomes
Outcome 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.
Outcome Time Frame
up to 1638 days
Outcome Measure
Percentage of Participants Attaining a Complete Response During Post-Baseline Visits
Outcome 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.
Outcome Time Frame
up to 1638 days
Outcome Measure
Percentage of Participants Attaining a Partial Response During Post-Baseline Visits
Outcome Description
Hemoglobin levels were assessed throughout the study.
Outcome Time Frame
up to 1638 days
Outcome Measure
Percentage of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From Baseline
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in Hemoglobin
Outcome Description
Percentage change from Baseline was calculated as: (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Percentage Change From Baseline in Hemoglobin
Outcome Description
A participant was defined to have required a transfusion if his or her last transfusion was within 7 days of the visit date.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Percentage of Participants Requiring Transfusions
Outcome Description
Normalization was determined by the Investigator based on normal ranges for the clinical reference laboratory.
Outcome Time Frame
up to 1638 days
Outcome Measure
Percentage of Participants Who Achieved Normalization of Hemoglobin, Haptoglobin, Lactate Dehydrogenase (LDH), Reticulocyte Count, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Outcome Description
Prednisone use was monitored throughout the study.
Outcome Time Frame
up to 1638 days
Outcome Measure
Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease)
Outcome 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.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale Scores
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean Cmax of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean Tmax of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean Cmin of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean AUC0-4 of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean AUC0-t of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean Clast of Parsaclisib
Outcome 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.
Outcome Time Frame
predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8
Outcome Measure
Mean Tlast of Parsaclisib
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in Reticulocyte Count
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; Week 12
Outcome Measure
Change From Baseline in Cardiolipin Immunoglobulin G (IgG) Antibody and Cardiolipin Immunoglobulin M (IgM) Antibody
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; Week 12
Outcome Measure
Change From Baseline in Cold Hemagglutinin Levels
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in Haptoglobin, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in Lactate Dehydrogenase (LDH)
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in CH50
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; up to 1638 days
Outcome Measure
Change From Baseline in Complement C3 and Complement C4
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO