A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

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

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.

Study Overview

• Status: Completed
• Conditions: Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: Parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 01090
    • Allgemeines Krankenhaus Der Stadt Wien
• France
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire (Chru) de Lille
• Italy
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Napoli, Italy, 80131
    • UNIVERSIT� DI NAPOLI FEDERICO II
  • Novara, Italy, 28100
    • AZIENDA OSPEDALIERO UNIVERSITARIA MAGGIORE DELLA CARIT� DI NOVARA
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University Health System Inc., Dba the University of Tn Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parsaclisib 1 mg QD; 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; Parsaclisib administered orally.; Other Names: INCB050465
Experimental: Parsaclisib 2.5 mg QD; Parsaclisib at 2.5 mg QD for 12 weeks followed by extension period.	Drug: Parsaclisib; Parsaclisib administered orally.; Other Names: INCB050465

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Kathleen Butler, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2018
• Primary Completion (Actual): August 5, 2021
• Study Completion (Actual): April 2, 2024

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: autoimmune hemolytic anemia; phosphatidylinositol 3-kinase (PI3K) inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: INCB 50465-206; Parsaclisib (Other Identifier: Incyte Corporation)

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