Warm antibody autoimmune hemolytic anemia (wAIHA) MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851
Conditions
Sponsors
Rigel Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be willing and able to give written informed consent by signing an IRB approved Informed Consent Form prior to undergoing any study-specific procedures. 2. Subject must have a diagnosis of primary or secondary wAIHA as documented by a positive direct antiglobulin test (DAT) specific for anti-IgG or anti-IgA. Eligibility may be based on a historical DAT obtained within 12 months of the screening visit from a local laboratory, provided that specific IgG or IgA positivity is documented; otherwise, this assay will be done at screening by a central laboratory. 3. Has failed or not tolerated at least one prior wAIHA treatment, e.g., steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil (MMF), danazol, vincristine, ESA or splenectomy (folate, iron or other supplements do not fulfill this criterion). 4. Has haptoglobin ULN or lactate dehydrogenase (LDH) >ULN. 5. At screening, subject’s hemoglobin level must be =9 g/dL OR If the hemoglobin value is >9 g/dL and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject with other types of AIHA (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria). 2. Subject has AIHA secondary to autoimmune disease, including systemic lupus erythematosus (SLE), or lymphoid malignancy if the underlying disease is not stable or is not well-controlled on current therapy, per investigator medical judgment. 3. Subject has a history of or active, clinically significant, cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the investigator’s opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study drug. 4. Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood pressure =135 mmHg or diastolic blood pressure =85 mmHg, whether or not the subject is receiving anti-hypertensive treatment. 5. Subject has one or more of the following laboratory abnormalities at screening: neutrophil count of 1.5 x ULN. 6. Has documented HIV infection or active hepatitis B or hepatitis C infection. 7. Subject is currently enrolled in an investigational drug or device study or has used an investigational drug or device within 30 days or 5 half-lives (whichever is longer) of Day 1. 8. In the judgment of the investigator, the subject may not be able to fully comply with study requirements. 9. Subject has been treated with fostamatinib previously for any indication. 10. Subject has a known allergy and/or sensitivity to the test article or its components. 11. Subject has had a splenectomy within the past 4 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA). ;Secondary Objective: The secondary objective of this study is to assess the safety of fostamatinib in subjects with wAIHA.;Primary end point(s): The primary efficacy endpoint is the proportion of subjects who achieve a durable response. A hemoglobin response is defined as a hemoglobin level of >10 g/dL and =2 g/dL higher than the baseline (Day 1) value if, during the previous 4 weeks, the steroid dose was maintained at the baseline level and rescue medication was not administered. A durable response is defined as a hemoglobin response on at least 3 scheduled visits during the 24-week evaluation period. ;Timepoint(s) of evaluation of this end point: 24 week evaluation | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 24 week evaluation;Secondary end point(s): • Proportion of subjects with a hemoglobin response by Week 24 • Proportion of subjects requiring wAIHA rescue therapy • Average number of weeks with hemoglobin response Safety Endpoints: • Incidence of adverse events • Incidence of abnormal changes from baseline in laboratory values per CTCAE criteria V 5.0 (e.g., hematology, chemistry) • Incidence of changes in blood pressure compared to baseline Exploratory endpoints: • Change from baseline in EQ-5D and FACIT-F domains at Week 24 • Median hemoglobin at Week 24 • Median change from baseline in hemoglobin at Week 24 • Median duration of the first hemoglobin response • Proportion of subjects who had =25% reduction from baseline in the total daily dose of steroids • Median cumulative dose of steroids (prednisone equivalent) Pharmacokinetic Endpoints: Plasma concentration of the active component of fostamatinib, (R406), at Weeks 2, 4, 12 and 18 of the treatment period. | — |
Countries
Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactSandra Tong
Rigel Pharmaceuticals, Inc.
Outcome results
None listed