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

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

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

Study Overview

• Status: Completed
• Conditions: Warm Antibody Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: Placebo; Drug: Fostamatinib disodium

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4201
      • Princess Alexandra Hospital - Cancer Trials Unit
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Universitätsklinik Innsbruck - Innere Medizin V
  • Salzburg, Austria, 5020
    • Universitätsklinikum Salzburg, 3.Medizin/Onkologie
  • Vienna, Austria, 1140
    • Hanusch-Krankenhaus
  • Wien, Austria, 1090
    • Medizinsche Universität Wien
• Belarus
  • Vitebsk, Belarus, 210037
    • Vitebsk Regional Clinical Hospital
  • Vitebsk, Belarus, 210603
    • Vitebsk Regional Clinical Oncology Dispensary
• Belgium
  • Antwerpen, Belgium, 2060
    • Ziekenhuis Network Antwerp, Stuivenberg
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen - Hematologie
  • Sint-Niklaas, Belgium, 9100
    • AZ Nikolaas
• Bulgaria
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment - Dr Georgi Stranski EAD, Pleven, Clinic of Clinical Haematology
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment 'Alexandrovska' EAD, Clinic of Clinical Haematology
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment 'Sv. Ivan Rilski' EAD, Clinic of Clinical Hematology, Department of Clinical Hematology
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment of Hematological Diseases EAD, Sofia, Clinic of Clinical Haematology
  • Varna, Bulgaria, 9010
    • University Multiprofile Hospital for Active Treatment 'Sveta Marina' EAD, Varna, Clinic of Clinical Haematology
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Hamilton Health Sciences- McMaster University Medical Centre
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno Interni hematologicka a onkologicka klinika
  • Ostrava, Czechia, 70852
    • Fakultni nemocnice Ostrava Klinika hematoonkologie
  • Praha, Czechia, 128 00
    • Ustav hematologie a krevni transfuze
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hopital
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital - Dept of Hematology
  • Herlev, Denmark, DK-2730
    • Herlev and Gentofte Hospital
• France
  • Angers, France, 49100
    • Chu Angers
  • Caen, France, 14033
    • Institut d'hématologie de Basse Normandie, CHU Caen
  • Clermont-Ferrand, France, 63003
    • CHU Estaing - Chirurgie digestive et Médecine interne
  • Créteil, France, 94000
    • Chu Henri Mondor
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Pessac, France, 33603
    • CHU de Bordeaux - GH Sud- Hôpital Haut Lévêque Service Médecine Interne et Maladies Infectieuses
  • Toulouse, France, 31100
    • CHU Toulouse, IUCT Oncopôle
• Georgia
  • Tbilisi, Georgia, 0186
    • ltd Multiprofile Clinic Consilium Medulla
  • Tbilisi, Georgia, 0112
    • M. Zodelava Hematology Centre, Tbilisi
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Leipzig, Germany, 04103
    • University of Leipzig Medical Center, Medical Department I - Haematology and Cell Therapy, Medical Oncology, Hemophilia
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem, Általános Orvostudományi Kar, I.sz. Belgyógyászati Klinika, Haematológiai Osztály,
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmár- Bereg Megyei Kórházak és Egyetemi Oktatókórház, Jósa András Oktatókórház
  • Pécs, Hungary, 7624
    • Pécsi Tudományegyetem, Klinikai Központ, I.számú Belgyógyászati Klinikai, Hematológiai Tanszék
• Italy
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia, Ematologia UOC
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico di Milano - UO Ematologia
  • Novara, Italy, 28100
    • SCDU Ematologia AOU "Maggiore della Carità"
  • Trieste, Italy, 34125
    • Ospedale Maggiore, SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina
  • Vicenza, Italy, 36100
    • ULSS8 Berica Ospedale San Bortolo - Unità Operativa Complessa di Ematologia
• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Grålum, Norway, 1714
    • Østfold Hopital
  • Ålesund, Norway, 6017
    • Ålesund Hospital
• Romania
  • Bucharest, Romania, 030171
    • Coltea Clinical Hospital
  • Bucharest, Romania, 050098
    • Emergency University Hospital Bucharest
  • Cluj-Napoca, Romania, 400015
    • "Prof. Dr. Ion Chiricuta" Institute of Oncology Cluj-Napoca
• Russian Federation
  • Moscow, Russian Federation, 125167
    • National Research Center for Hematology
  • Moscow, Russian Federation, 125284
    • Botkin Moscow City Clinical Hospital
  • Moscow, Russian Federation, 129301
    • State Budgetary Healthcare Institution of Moscow city "City Clinical Hospital No 40 Department of Healthcare of Moscow city"
  • Novosibirsk, Russian Federation, 630051
    • State Budgetary Healthcare Institution of Novosibirsk Region "City Clinical Hospital №2"
  • Sochi, Russian Federation, 354057
    • State Budgetary Healthcare Institution Oncology Dispensary No. 2 of the Ministry of Health of the Krasnodar Territory
  • Tomsk, Russian Federation, 634063
    • Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"
• Serbia
  • Belgrade, Serbia, 11080
    • University Hospital Medical Center "Bezanijska Kosa", Department of Hematology
  • Niš, Serbia, 18000
    • Clinical Center Nis, Clinic for Hematology
  • Novi Sad, Serbia, 21000
    • Clinical Centre of Vojvodina, Clinic for Hematology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Madrid, Spain, 28009
    • Hospital Universitario Gregorio Maranon
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe - Servicio de Hematología
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Regional Oncology Dispensary, Hematology Center
  • Dnipro, Ukraine, 49102
    • City Clinical Hospital № 4, Hematology Center
  • Kyiv, Ukraine, 04112
    • Kyiv City Clinical Hospital №9, hematology department №1
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, Liverpool University Hospitals NHS Foundation Trust
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • The Royal London Hospital, Bart's Health NHS Trust
  • West Bromwich, United Kingdom, B71 4HJ
    • Sandwell and West Birmingham NHS Trust
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • East Kent Haemophilia Centre, Kent and Canterbury Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC--HOPE Division
  • California
    • La Jolla, California, United States, 92037
      • Moores UC San Diego Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Torrance, California, United States, 90502
      • Harbor UCLA - Lundquist Institute
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Greeley, Colorado, United States, 80538
      • Banner MD Anderson Cancer Center at North Colorado Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University - Lombardi Comprehensive Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Affiliated Oncologists
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • John Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers - Robert Wood Johnson Medical School
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Clayton, North Carolina, United States, 27520
      • Duke Cancer Network
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Research Institute
    • Webster, Texas, United States, 77598
      • Clear Lake Specialties, Research Dept.
  • Washington
    • Olympia, Washington, United States, 98506
      • American Oncology Network Vista Oncology Division
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98109
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Versiti Wisconsin, Inc.
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Clinic Cancer Center - Stevens Point

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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
Placebo Comparator: 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.	Drug: Placebo; Placebo

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

Collaborators and Investigators

• Sponsor: Rigel Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2019
• Primary Completion (Actual): April 11, 2022
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: wAIHA; Warm Antibody Autoimmune Hemolytic Anemia; Warm Autoimmune Hemolytic Anemia
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: C-935788-057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No