Autoimmune Hemolytic Anemia (AIHA), immunohemolytic anemia, autoimmune hemolytic anemia, immune complex hemolytic anemia. Warm AIHA, Cold AIHA MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851
Conditions
Interventions
Product Code: INCB050465 1 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: not yet assigned
Current Sponsor code: INCB050465
Other descriptive name: INCB050465 HYDROCHLORIDE
Concentration unit: mg
Sponsors
Incyte Coorporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant who meets all of the following criteria may be included in the study: 1. Men or women, aged 18 years or older. 2. Diagnosis of AIHA based on the presence of hemolytic anemia and serological evidence of anti-erythrocyte antibodies, detectable by the DAT as follows: a. Warm: DAT positive for IgG only or IgG plus C3d b. Cold (CAD): DAT positive for C3d only, with cold agglutinins of I specificity c. Mixed: DAT positive for IgG and C3d, with coexistence of warm autoantibodies and high titer cold agglutinins 3. 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. 4. Hemoglobin 7 to 10 g/dL. (as determined by local laboratory). 5. No evidence of a lymphoproliferative malignancy or other autoimmune-related underlying conditions (eg, systemic lupus erythematosus, Castleman's disease, Sjögren's syndrome, or other autoimmune diseases). 6. ECOG performance status score of 0 to 2. 7. Willingness to avoid pregnancy or fathering children based on the criteria below: a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined by last menstrual period > 12 months before screening and confirmed by FSH). b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through at least 93 days after the last dose of study drug. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and her understanding confirmed. c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 93 days after the last dose of study drug. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and his understanding confirmed. 8. Able to comprehend and willing to sign an ICF. 9. Willingness to receive PJP prophylaxis during the study period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: A participant who meets any of the following criteria will be excluded from the study: 1. Pregnant or breastfeeding women. 2. Concurrent conditions and history of other diseases: a. History or clinical manifestations of significant unstable metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders. b. Current or previous malignancy within 5 years of study entry, except basal or squamous cell skin cancer with removal considered to be curative, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval. c. Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, and or cardiac conduction issues within 6 months of the date of study drug administration. d. Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia. 3. Inadequate hematologic function defined as follows (as determined by local laboratory): a. ANC 470 milliseconds for males and > 480 milliseconds for females (corrected by Fridericia) are excluded. In the event that a single QTcF is >470 milliseconds for males or >480 milliseconds for females, the participant may enroll if the average QTcF for 3 ECGs is <470 milliseconds for males and <480 milliseconds for females. 10. Use of the following medications: a. Treatment with rituximab within 3 months of the baseline visit. b. Use of immunosuppressive therapy within 28 days of the baseline visit. Immunosuppressive therapy includes, but is not limited to, cyclosporine A, tacrolimus, or high-dose corticosteroids. Participants receiving corticosteroids must be at a dose level = 20 mg/day (prednisone or equivalent corticosteroid dose) within 14 days of the baseline visit. c. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 28 days of the baseline visit. d. Use or expected use during the study of any prohibited medications, including potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the baseline visit. e. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication, or cu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of INCB050465 in the treatment of participants with AIHA. • Proportion of participants attaining a CR (defined as hemoglobin > 12 g/dL not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12. • Proportion of participants attaining a PR (defined as hemoglobin 10-12 g/dL or = 2 g/dL increase from baseline not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12. To evaluate the safety of INCB050465 administered as repeat doses in participants with AIHA. • Safety and tolerability will be assessed by monitoring AEs, measuring vital signs and ECGs, and conducting clinical laboratory blood and urine sample assessments. ;Secondary Objective: To further evaluate the efficacy of INCB050465 in the treatment of participants with AIHA. • Proportion of participants attaining a CR during postbaseline visits. • Proportion of participants attaining a PR during postbaseline visits. • Proportion of participants attaining a = 2 g/dL increase in hemoglobin from baseline. • Mean, change, and percentage change from baseline of hemoglobin. • Proportion of participants requiring transfusions. • Proportion of participants who achieve normalization of hemolytic markers. (Hemolysis markers: hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin, and direct/indirect bilirubin.) • Change of daily usage of prednisone. • FACIT-F sub-scale assessment. ;Primary end point(s): Proportion of participants attaining a CR (defined as hemoglobin >12 g/dL not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12. • Proportion of participants attaining a PR (defined as hemoglobin 10-12 g/dL or at least = 2 g/dL increase from baseline not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12. ;Timepoint(s) o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of participants attaining a CR during postbaseline visits. • Proportion of participants attaining a PR during postbaseline visits. • Proportion of participants attaining a = 2 g/dL increase in hemoglobin from baseline. • Mean, change, and percentage change from baseline of hemoglobin. • Proportion of participants requiring transfusions. • Proportion of participants who achieve normalization of hemolytic markers. (Hemolysis markers: hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin, and direct/indirect bilirubin.) • Change of daily usage of prednisone. • FACIT-F sub-scale assessment.;Timepoint(s) of evaluation of this end point: Efficacy: Throughout the study PK: Week 1: predose; week 2 and week 8: predose, at 1h +- 10min, at 2h +- 10min and at 4h +- 30 min; week 12: predose PD: DAT for IgG and C3b and cold agglutinin levels: at screening and week 12; reticulocyte count, haptoglobin, total bilirubin, direct/indirect bilirubin, and LDH: at screening, day 1, weeks 1, 2, 4, 6, 8 and 10; complement assessment (CH50, C3, and C4): at day 1 and week 12 | — |
Countries
Austria, France, Italy, United States
Contacts
Public ContactMedical Information
Incyte Corporation
Outcome results
None listed