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A Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03538041
Recruitment Status : Active, not recruiting
First Posted : May 25, 2018
Results First Posted : September 22, 2022
Last Update Posted : September 22, 2022
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

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.

Condition or disease Intervention/treatment Phase
Autoimmune Hemolytic Anemia Drug: Parsaclisib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia
Actual Study Start Date : November 21, 2018
Actual Primary Completion Date : August 5, 2021
Estimated Study Completion Date : September 8, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

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 Name: 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 Name: INCB050465




Primary Outcome Measures :
  1. Percentage of Participants Attaining a Complete Response at Any Visit From Week 6 to Week 12 [ Time Frame: 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.

  2. Percentage of Participants Attaining a Partial Response at Any Visit From Week 6 to Week 12 [ Time Frame: 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.

  3. Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Treatment Period [ Time Frame: up to a maximum of 99 days ]
    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 :
  1. Number of Participants With Any TEAE in the Extension Period [ Time Frame: up to approximately 3 years ]
    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.

  2. Percentage of Participants Attaining a Complete Response During Post-Baseline Visits [ Time Frame: up to approximately 2.5 years ]
    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.

  3. Percentage of Participants Attaining a Partial Response During Post-Baseline Visits [ Time Frame: up to approximately 2.5 years ]
    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.

  4. Percentage of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From Baseline [ Time Frame: up to approximately 2.5 years ]
    Hemoglobin levels were assessed throughout the study.

  5. Change From Baseline in Hemoglobin [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  6. Percentage Change From Baseline in Hemoglobin [ Time Frame: Baseline; up to approximately 2.5 years ]
    Percentage change from Baseline was calculated as: ([post-Baseline value minus the Baseline value] / Baseline value) x 100.

  7. Percentage of Participants Requiring Transfusions [ Time Frame: Baseline; up to approximately 2.5 years ]
    A participant was defined to have required a transfusion if his or her last transfusion was within 7 days of the visit date.

  8. Percentage of Participants Who Achieved Normalization of Hemoglobin, Haptoglobin, Lactate Dehydrogenase (LDH), Reticulocyte Count, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin [ Time Frame: up to approximately 2.5 years ]
    Normalization was determined by the Investigator based on normal ranges for the clinical reference laboratory.

  9. Percentage of Participants Requiring a Prednisone Dose Change (Increase or Decrease) [ Time Frame: up to approximately 2.5 years ]
    Prednisone use was monitored throughout the study.

  10. Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale Scores [ Time Frame: Baseline; up to approximately 2.5 years ]
    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.

  11. Mean Cmax of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    Cmax was defined as the maximum observed concentration. Participants in Cohort 1 were not eligible to receive parsaclisib 2.5 mg at Week 2.

  12. Mean Tmax of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  13. Mean Cmin of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  14. Mean AUC0-4 of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  15. Mean AUC0-t of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  16. Mean Clast of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  17. Mean Tlast of Parsaclisib [ Time Frame: predose at Weeks 1 and 12; predose and 1, 2, and 4 hours postdose at Weeks 2 and 8 ]
    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.

  18. Change From Baseline in Reticulocyte Count [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value

  19. Change From Baseline in Direct Antiglobulin Test (DAT) for Immunoglobulin G (IgG) and C3b [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  20. Change From Baseline in Cold Agglutinin Levels [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  21. Change From Baseline in Haptoglobin, Total Bilirubin, Direct Bilirubin, and Indirect Bilirubin [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  22. Change From Baseline in LDH [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  23. Change From Baseline in CH50 [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  24. Change From Baseline in C3 and C4 [ Time Frame: Baseline; up to approximately 2.5 years ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03538041


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

Documents provided by Incyte Corporation:
Study Protocol  [PDF] November 2, 2020
Statistical Analysis Plan  [PDF] March 3, 2022

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03538041    
Other Study ID Numbers: INCB 50465-206
Parsaclisib ( Other Identifier: Incyte Corporation )
First Posted: May 25, 2018    Key Record Dates
Results First Posted: September 22, 2022
Last Update Posted: September 22, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
autoimmune hemolytic anemia
phosphatidylinositol 3-kinase (PI3K) inhibitor
Additional relevant MeSH terms:
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Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases