Warm Antibody Autoimmune Hemolytic Anemia
Conditions
Keywords
wAIHA, Warm Antibody Autoimmune Hemolytic Anemia, Warm Autoimmune Hemolytic Anemia
Brief summary
The primary objective of this study is to assess the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA).
Interventions
DRUGPlacebo
Placebo
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.
Sponsors
Rigel Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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). 3. Have haptoglobin \<LLN or total bilirubin \>ULN or lactate dehydrogenase (LDH) \>ULN. 4. 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). 5. Karnofsky performance status (KPS) ≥70. 6. 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
1. 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). 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 judgement. 3. 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. 4. 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. 5. Has documented active hepatitis B or hepatitis C infection or HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable Hemoglobin Response | 24 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A Hemoglobin Response by Week 24 | 24 weeks | Proportion of subjects with a hemoglobin response by Week 24. |
| Change From Baseline in Hemoglobin Level of 2 g/dL or Greater | 24 weeks | Proportion of subjects with change from baseline in hemoglobin level of 2 g/dL or greater. |
| Change in Hemoglobin From Baseline to End of Treatment | 24 weeks | Change in mean hemoglobin from baseline to end of treatment. |
| Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4 | 24 weeks | Proportion of subjects free of rescue AIHA regimens used after Week 4. |
| Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) | 24 weeks | 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 \[N of items in subscale\] ÷ \[N of items answered\]. |
Countries
Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russia, Serbia, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fostamatinib 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.
Fostamatinib disodium: 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 once a day (qd) or matching placebo if dose limiting adverse events are observed. | 45 |
| Placebo 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.
Placebo: Placebo | 45 |
| Total | 90 |
Baseline characteristics
| Characteristic | Fostamatinib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.8 Years STANDARD_DEVIATION 15.32 | 59.9 Years STANDARD_DEVIATION 15.7 | 58.4 Years STANDARD_DEVIATION 15.5 |
| Age, Customized < 65 years | 29 Participants | 23 Participants | 52 Participants |
| Age, Customized ≥ 65 years | 16 Participants | 22 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 40 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 38 Participants | 43 Participants | 81 Participants |
| Region of Enrollment Australia | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Austria | 2 Participants | 4 Participants | 6 Participants |
| Region of Enrollment Belarus | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Belgium | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Bulgaria | 5 Participants | 10 Participants | 15 Participants |
| Region of Enrollment Canada | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Czechia | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment France | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Georgia | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Germany | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Italy | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Netherlands | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Norway | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Russia | 5 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Serbia | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Spain | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Ukraine | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 28 Participants | 27 Participants | 55 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 45 | 3 / 45 |
| other Total, other adverse events | 42 / 45 | 40 / 45 |
| serious Total, serious adverse events | 15 / 45 | 17 / 45 |
Outcome results
Primary
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.
Time frame: 24 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib | Durable Hemoglobin Response | 16 Participants |
| Placebo | Durable Hemoglobin Response | 12 Participants |
Secondary
A Hemoglobin Response by Week 24
Proportion of subjects with a hemoglobin response by Week 24.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib | A Hemoglobin Response by Week 24 | 21 Participants |
| Placebo | A Hemoglobin Response by Week 24 | 16 Participants |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib | Change From Baseline in Hemoglobin Level of 2 g/dL or Greater | 22 Participants |
| Placebo | Change From Baseline in Hemoglobin Level of 2 g/dL or Greater | 16 Participants |
Secondary
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 \[N of items in subscale\] ÷ \[N of items answered\].
Time frame: 24 weeks
Population: The analysis population includes the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib | Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) | 4.1 score on a scale | Standard Deviation 12.86 |
| Placebo | Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) | 2.2 score on a scale | Standard Deviation 11.03 |
Secondary
Change in Hemoglobin From Baseline to End of Treatment
Change in mean hemoglobin from baseline to end of treatment.
Time frame: 24 weeks
Population: Of the 72 completed participants, 11 participants were excluded due to hemoglobin value missing or not being eligible during the evaluation period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib | Change in Hemoglobin From Baseline to End of Treatment | 1.99 g/dL | Standard Deviation 2.095 |
| Placebo | Change in Hemoglobin From Baseline to End of Treatment | 1.99 g/dL | Standard Deviation 2.468 |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib | Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4 | 18 Participants |
| Placebo | Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4 | 18 Participants |