A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

Conditions
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Autoimmune Hemolytic Anemia

Intervention / Treatment
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* Drug: Parsaclisib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parsaclisib 1 mg QD<br>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. | Drug: Parsaclisib<br>* Parsaclisib administered orally.<br>* Other names: INCB050465;|
| Experimental: Parsaclisib 2.5 mg QD<br>Parsaclisib at 2.5 mg QD for 12 weeks followed by extension period. | Drug: Parsaclisib<br>* Parsaclisib administered orally.<br>* Other names: INCB050465;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 6 to Week 12 | 
| 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. | Week 6 to Week 12 | 
| 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. | up to a maximum of 99 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to approximately 3 years | 
| 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. | up to approximately 2.5 years | 
| 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. | up to approximately 2.5 years | 
| Percentage of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From Baseline | Hemoglobin levels were assessed throughout the study. | up to approximately 2.5 years | 
| Change From Baseline in Hemoglobin | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; up to approximately 2.5 years | 
| Percentage Change From Baseline in Hemoglobin | Percentage change from Baseline was calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) x 100. | Baseline; up to approximately 2.5 years | 
| 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. | Baseline; up to approximately 2.5 years | 
| 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. | up to approximately 2.5 years | 
| Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease) | Prednisone use was monitored throughout the study. | up to approximately 2.5 years | 
| 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. | Baseline; up to approximately 2.5 years | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| 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. | predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 | 
| Change From Baseline in Reticulocyte Count | Change from Baseline was calculated as the post-Baseline value minus the Baseline value | Baseline; up to approximately 2.5 years | 
| 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. | Baseline; up to approximately 2.5 years | 
| Change From Baseline in Cold Agglutinin Levels | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; up to approximately 2.5 years | 
| 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. | Baseline; up to approximately 2.5 years | 
| Change From Baseline in LDH | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; up to approximately 2.5 years | 
| Change From Baseline in CH50 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; up to approximately 2.5 years | 
| Change From Baseline in C3 and C4 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; up to approximately 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autoimmune hemolytic anemia, phosphatidylinositol 3-kinase (PI3K) inhibitor