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

• ClinicalTrials.gov Identifier: NCT03764618
• Recruitment Status: Recruiting
• First Posted: December 5, 2018
• Last Update Posted: December 11, 2019
• Sponsor: Rigel Pharmaceuticals
• Information provided by (Responsible Party): Rigel Pharmaceuticals

Tracking Information

• First Submitted Date: December 3, 2018
• First Posted Date: December 5, 2018
• Last Update Posted Date: December 11, 2019
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 3, 2018)

Durable Hemoglobin Response [ Time Frame: 24 Weeks ]

The primary efficacy endpoint is the proportion of subjects who achieve a durable hemoglobin response.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03764618 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 3, 2018)

• Subjects with a hemoglobin response by Week 24 [ Time Frame: 24 weeks ]
  Proportion of subjects with a hemoglobin response by Week 24
• Frequency of rescue AIHA regimens used [ Time Frame: 24 weeks ]
  Average frequency of rescue AIHA regimens used
• Hemoglobin assessments exhibiting a hemoglobin response [ Time Frame: 24 weeks ]
  Average number of hemoglobin assessments exhibiting a hemoglobin response

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of 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
• Brief Summary: The primary objective of this study is to assess the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Warm Antibody Autoimmune Hemolytic Anemia

Intervention

• Drug: 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 qd or matching placebo if dose limiting adverse events are observed.

  Other Names:

  • R935788
  • Fostamatinib
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Fostamatinib
  Initial dose is 100 mg PO 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.
  Intervention: Drug: Fostamatinib disodium
• Placebo Comparator: Placebo
  Initial dose is 100 mg PO 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.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 3, 2018): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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.
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. Male or female at least 18 years of age at screening.
6. Karnofsky performance status (KPS) ≥70.
7. 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Australia, Georgia, Russian Federation, United States

Administrative Information

• NCT Number: NCT03764618
• Other Study ID Numbers: C-935788-057
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Rigel Pharmaceuticals
• Study Sponsor: Rigel Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rigel Pharmaceuticals
• Verification Date: April 2019