This is a Phase 3 multi-center, randomized, double-blind, placebo-controlled, parallel group study to investigate the efficacy of 24 weeks of treatment with fostamatinib (R935788) vs. placebo in achieving a durable hemoglobin response in subjects with wAIHA who have failed at least one prior treatment regimen.

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2018-004774-97-CZ
• Date of registration: 13/06/2019
• Prospective Registration: Yes
• Primary sponsor: Rigel Pharmaceuticals, Inc.
• Public title: This is a Phase 3 multi-center, randomized, double-blind, placebo-controlled, parallel group study to investigate the efficacy of 24 weeks of treatment with fostamatinib (R935788) vs. placebo in achieving a durable hemoglobin response in subjects with wAIHA who have failed at least one prior treatment regimen.
• Scientific title: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia
• Date of first enrolment: 05/09/2019
• Target sample size: 90
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004774-97
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Czechia, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Sandra Tong
• Affiliation: Rigel Pharmaceuticals, Inc.

• Name: Sandra Tong
• Affiliation: Rigel Pharmaceuticals, Inc.

Key inclusion & exclusion 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 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 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 <10 g/dL, subject must be on an allowed wAIHA treatment (see Allowed AIHA Therapy table) AND the subject must have documented symptoms related to anemia (e.g., weakness, dizziness, fatigue, shortness of breath, chest pain).
6. Male or female at least 18 years of age at screening.
7. Karnofsky performance status (KPS) =70.
8. 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, as defined in the Allowed AIHA Therapies table. Subject has not taken any disallowed therapies in the intervals defined by the Protocol.
9. Female subjects must be either post-menopausal for at least 1 year or surgically sterile; or, if of childbearing potential, must not be pregnant or lactating and must agree to use a highly effective method of birth control throughout the duration of the trial and for 30 days following the last dose. Acceptable methods of birth control are defined as: hormonal contraception (pill, injection or implant) used consistently for at least 30 days prior to screening, an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS) or true abstinence (i.e. abstinence is in line with the preferred and usual lifestyle of the subject).
10. In the investigator’s opinion, the subject has the ability to understand the nature of the study and any hazards of participation and to communicate satisfactorily with the investigator.

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 90
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 <1,000/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.
6. Has documented active hepatitis B or hepatitis C infection or HIV 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Warm antibody autoimmune hemolytic anemia (wAIHA)
MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851

Intervention(s)

Product Name: Fostamatinib Disodium
Product Code: R935788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib
CAS Number: 914295-16-2
Current Sponsor code: Fostamatinib Disodium R935788
Other descriptive name: R788, fostamatinib disodium hexahydrate (in USPI/FPI)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Fostamatinib Disodium
Product Code: R935788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib
CAS Number: 914295-16-2
Current Sponsor code: Fostamatinib Disodium R935788
Other descriptive name: R788, fostamatinib disodium hexahydrate (in USPI/FPI)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To compare the proportion of subjects with hemoglobin response on at least one visit between the fostamatinib and placebo groups.
To compare the proportion of subjects who achieve a change from Baseline in hemoglobin level of = 2 g/dL between the fostamatinib and placebo groups.
To compare the proportion of subjects who use permitted rescue medications after Week 4 between the fostamatinib and placebo groups.
To compare the change in hemoglobin value from Baseline to the End of Treatment between the fostamatinib and placebo groups.
The safety objective is to assess the safety of fostamatinib in subjects with wAIHA.
Additional efficacy and pharmacoeconomic objectives will compare the fostamatinib and placebo groups for the endpoints noted below.

Timepoint(s) of evaluation of this end point: 24 week evaluation

Main Objective: The primary objective of this study is to compare the proportion of warm antibody autoimmune hemolytic anemia (wAIHA) subjects who achieve a durable hemoglobin response between the fostamatinib and placebo groups.

Primary end point(s): The primary efficacy endpoint is achievement of durable hemoglobin response (Yes/No) defined as 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, in which hemoglobin measurements eligible for this definition occurred outside a Rescue Treatment Visit Exclusion Period.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints within the 24 weeks of treatment are:
•Hemoglobin response on at least one visit (Yes/No)
•Achievement of a change from Baseline in hemoglobin level of 2 g/dL or greater (Yes/No)
•Use of permitted rescue medications after Week 4 (Yes/No)
•Change in hemoglobin value from Baseline to End of Treatment

Safety Endpoints:
The following safety endpoints will be evaluated:
•Incidence and severity of treatment-emergent adverse events (TEAEs)
•Change from Baseline for select laboratory tests over time (e.g., hematology, chemistry)
•Change from Baseline in blood pressure over time
•Change from Baseline in absolute neutrophil count (ANC) over time
•Change from Baseline in liver function tests (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST]), total bilirubin, direct and indirect bilirubin) over time.

Pharmacokinetic Endpoints:
Plasma concentration of the active component of fostamatinib (R406) relative to the date and time of last dose of study drug, at Weeks 2, 4, 12 and 18 of the treatment period.

Timepoint(s) of evaluation of this end point: 24 week evaluation

Secondary ID(s)

2018-004774-97-GB

C-935788-057

Source(s) of Monetary Support

Rigel Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 15/08/2019
Contact: