A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of wAIHA

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to assess the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA).

Official Title
-----------------
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia

Conditions
-----------------
Warm Antibody Autoimmune Hemolytic Anemia

Intervention / Treatment
-----------------
* Drug: Fostamatinib disodium
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have a diagnosis of primary or secondary warm Antibody Autoimmune Hemolytic Anemia (wAIHA) as documented by a positive direct antiglobulin test (DAT) specific for anti-IgG or anti-IgA. Have failed or not tolerated at least one prior wAIHA treatment regimen, including steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, MMF, danazol, vincristine, ESA or splenectomy (folate, iron or other supplements do not fulfill this criterion). Have haptoglobin <LLN or total bilirubin >ULN or lactate dehydrogenase (LDH) >ULN. At screening, subject's hemoglobin level must be ≤9 g/dL OR if hemoglobin value >9 g/dL and <10 g/dL, subject must be on an allowed wAIHA treatment AND the subject must have documented symptoms related to anemia (e.g., weakness, dizziness, fatigue, shortness of breath, chest pain). Karnofsky performance status (KPS) ≥70. Subject's concurrent treatment for wAIHA may consist of no more than two of any of the following agents: azathioprine, steroids, ESAs, mycophenolate mofetil, dapsone or danazol at a stable dose Exclusion Criteria: Subject with other types of Antibody Autoimmune Hemolytic Anemia (AIHA) (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria). 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 judgement. 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. Subject has one or more of the following laboratory abnormalities at screening: neutrophil count of <1,000/μL or platelet count of <30,000/μL, unless due to Evans syndrome; transaminase levels (i.e., alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) >1.5 x ULN. Has documented active hepatitis B or hepatitis C infection or HIV infection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fostamatinib<br>Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. | Drug: Fostamatinib disodium<br>* Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.<br>* Other names: Fostamatinib;|
| Placebo Comparator: Placebo<br>Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durable Hemoglobin Response | Proportion of subjects achieving a hemoglobin level ≥ 10 g/dL with an increase from Baseline in hemoglobin level of ≥ 2 g/dL on 3 consecutive available visits during the 24-week treatment period. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Hemoglobin Response by Week 24 | Proportion of subjects with a hemoglobin response by Week 24. | 24 weeks | 
| Change From Baseline in Hemoglobin Level of 2 g/dL or Greater | Proportion of subjects with change from baseline in hemoglobin level of 2 g/dL or greater. | 24 weeks | 
| Change in Hemoglobin From Baseline to End of Treatment | Change in mean hemoglobin from baseline to end of treatment. | 24 weeks | 
| Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4 | Proportion of subjects free of rescue AIHA regimens used after Week 4. | 24 weeks | 
| Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) | Change from Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). The FACIT-F scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. Each item is rated using a 5-point Likert-type scale. The scale range is 0 to 52, with 0 being the worst possible score and 52 being the best possible score indicating no fatigue. Total Score = [Sum of item scores] x [N of items in subscale] ÷ [N of items answered]. | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
wAIHA, Warm Antibody Autoimmune Hemolytic Anemia, Warm Autoimmune Hemolytic Anemia