A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

Autoimmune Hemolytic Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03538041
• Other study ID #: INCB 50465-206
• Secondary ID: Parsaclisib
• Status: Completed
• Phase: Phase 2
• Start date: November 21, 2018
• Est. completion date: April 2, 2024

Study information

• Verified date: April 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2, 2024
• Est. primary completion date: August 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Anemia
• Hemolysis

Intervention

Drug:
• Parsaclisib
Parsaclisib administered orally.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease)	Prednisone use was monitored throughout the study.	up to approximately 2.5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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