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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 6 October 2020
Main ID:  EUCTR2018-004774-97-DK
Date of registration: 20/06/2019
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 (R788) vs. placebo in increasing hemoglobin in subjects with warm antibody autoimmune hemolytic anemia (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: 15/11/2019
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 Denmark
France Georgia Germany Hungary Italy Netherlands Norway Romania
Russian Federation Serbia Spain Ukraine United Kingdom United States
Contacts
Name: Sandra Tong   
Address:  1180 Veterans Boulevard CA 94080 South San Francisco United States
Telephone: +1 650-624-1207
Email: stong@rigel.com
Affiliation:  Rigel Pharmaceuticals, Inc.
Name: Sandra Tong   
Address:  1180 Veterans Boulevard CA 94080 South San Francisco United States
Telephone: +1 650-624-1207
Email: stong@rigel.com
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 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 <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 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.



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)
Main Objective: The primary objective of this study is to assess the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (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.
Secondary Objective: The secondary objective of this study is to assess the safety of fostamatinib in subjects with wAIHA.
Timepoint(s) of evaluation of this end point: 24 week evaluation
Secondary Outcome(s)
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.

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.
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 15/11/2019
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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