A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of wAIHA
- Conditions
- Warm Antibody Autoimmune Hemolytic Anemia
- Interventions
- Drug: Placebo
- Registration Number
- NCT03764618
- Lead Sponsor
- Rigel Pharmaceuticals
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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.
- 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).
- Have haptoglobin <LLN or total bilirubin >ULN or lactate dehydrogenase (LDH) >ULN.
- 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).
- Karnofsky performance status (KPS) ≥70.
- 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
- 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).
- 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.
- 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.
- 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.
- Has documented active hepatitis B or hepatitis C infection or HIV infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fostamatinib Fostamatinib disodium 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. Placebo 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 \[N of items in subscale\] ÷ \[N of items answered\].
Trial Locations
- Locations (102)
Piedmont Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Concord Repatriation General Hospital
🇦🇺Sydney, New South Wales, Australia
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Marshfield Clinic Cancer Center - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Hanusch-Krankenhaus
🇦🇹Vienna, Austria
Ziekenhuis Network Antwerp, Stuivenberg
🇧🇪Antwerpen, Belgium
"Prof. Dr. Ion Chiricuta" Institute of Oncology Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
University of Washington
🇺🇸Seattle, Washington, United States
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Aalborg University Hopital
🇩🇰Aalborg, Denmark
Moores UC San Diego Cancer Center
🇺🇸La Jolla, California, United States
Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico di Milano - UO Ematologia
🇮🇹Milano, Italy
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Aarhus University Hospital - Dept of Hematology
🇩🇰Aarhus N, Denmark
Herlev and Gentofte Hospital
🇩🇰Herlev, Denmark
Vitebsk Regional Clinical Hospital
🇧🇾Vitebsk, Belarus
Institut d'hématologie de Basse Normandie, CHU Caen
🇫🇷Caen, France
Clear Lake Specialties, Research Dept.
🇺🇸Webster, Texas, United States
Ustav Hematologie a Krevni Transfuze
🇨🇿Praha, Czechia
American Oncology Network Vista Oncology Division
🇺🇸Olympia, Washington, United States
Princess Alexandra Hospital - Cancer Trials Unit
🇦🇺Brisbane, Queensland, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Medizinsche Universität Wien
🇦🇹Wien, Austria
SCDU Ematologia AOU "Maggiore della Carità"
🇮🇹Novara, Italy
M. Zodelava Hematology Centre, Tbilisi
🇬🇪Tbilisi, Georgia
Universitätsklinikum Essen
🇩🇪Essen, Germany
Fakultni nemocnice Ostrava Klinika hematoonkologie
🇨🇿Ostrava, Czechia
Semmelweis Egyetem, Általános Orvostudományi Kar, I.sz. Belgyógyászati Klinika, Haematológiai Osztály,
🇭🇺Budapest, Hungary
Vitebsk Regional Clinical Oncology Dispensary
🇧🇾Vitebsk, Belarus
Hôpital Saint Antoine
🇫🇷Paris, France
Pécsi Tudományegyetem, Klinikai Központ, I.számú Belgyógyászati Klinikai, Hematológiai Tanszék
🇭🇺Pécs, Hungary
CHU Toulouse, IUCT Oncopôle
🇫🇷Toulouse, France
CHU Henri Mondor
🇫🇷Créteil, France
Fakultni nemocnice Brno Interni hematologicka a onkologicka klinika
🇨🇿Brno, Czechia
University of Leipzig Medical Center, Medical Department I - Haematology and Cell Therapy, Medical Oncology, Hemophilia
🇩🇪Leipzig, Germany
CHU Estaing - Chirurgie digestive et Médecine interne
🇫🇷Clermont-Ferrand, France
CHU de Bordeaux - GH Sud- Hôpital Haut Lévêque Service Médecine Interne et Maladies Infectieuses
🇫🇷Pessac, France
Ålesund Hospital
🇳🇴Ålesund, Norway
Emergency University Hospital Bucharest
🇷🇴Bucharest, Romania
Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
National Research Center for Hematology
🇷🇺Moscow, Russian Federation
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
The Royal London Hospital, Bart's Health NHS Trust
🇬🇧London, United Kingdom
Botkin Moscow City Clinical Hospital
🇷🇺Moscow, Russian Federation
East Kent Haemophilia Centre, Kent and Canterbury Hospital
🇬🇧Canterbury, Kent, United Kingdom
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
Clinical Center Nis, Clinic for Hematology
🇷🇸Niš, Serbia
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Cherkasy Regional Oncology Dispensary, Hematology Center
🇺🇦Cherkasy, Ukraine
State Budgetary Healthcare Institution of Moscow city "City Clinical Hospital No 40 Department of Healthcare of Moscow city"
🇷🇺Moscow, Russian Federation
Banner MD Anderson Cancer Center at North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Harbor UCLA - Lundquist Institute
🇺🇸Torrance, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Georgetown University - Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Affiliated Oncologists
🇺🇸Chicago Ridge, Illinois, United States
Rutgers - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
John Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Texas Oncology - Baylor Research Institute
🇺🇸Dallas, Texas, United States
Universitätsklinik Innsbruck - Innere Medizin V
🇦🇹Innsbruck, Austria
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
University Multiprofile Hospital for Active Treatment 'Alexandrovska' EAD, Clinic of Clinical Haematology
🇧🇬Sofia, Bulgaria
Hamilton Health Sciences- McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
LTD Multiprofile Clinic Consilium Medulla
🇬🇪Tbilisi, Georgia
CHU Angers
🇫🇷Angers, France
Haukeland University Hospital
🇳🇴Bergen, Norway
ASST degli Spedali Civili di Brescia, Ematologia UOC
🇮🇹Brescia, Italy
Ospedale Maggiore, SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina
🇮🇹Trieste, Italy
ULSS8 Berica Ospedale San Bortolo - Unità Operativa Complessa di Ematologia
🇮🇹Vicenza, Italy
State Budgetary Healthcare Institution Oncology Dispensary No. 2 of the Ministry of Health of the Krasnodar Territory
🇷🇺Sochi, Russian Federation
University Hospital Medical Center "Bezanijska Kosa", Department of Hematology
🇷🇸Belgrade, Serbia
State Budgetary Healthcare Institution of Novosibirsk Region "City Clinical Hospital №2"
🇷🇺Novosibirsk, Russian Federation
Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"
🇷🇺Tomsk, Russian Federation
Hospital Universitario Puerta de Hierro de Majadahonda
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario y Politecnico La Fe - Servicio de Hematología
🇪🇸Valencia, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hammersmith Hospital
🇬🇧London, United Kingdom
City Clinical Hospital № 4, Hematology Center
🇺🇦Dnipro, Ukraine
Sandwell and West Birmingham NHS Trust
🇬🇧West Bromwich, United Kingdom
Duke Cancer Network
🇺🇸Clayton, North Carolina, United States
Arizona Oncology Associates, PC--HOPE Division
🇺🇸Tucson, Arizona, United States
AZ Nikolaas
🇧🇪Sint-Niklaas, Belgium
Østfold Hopital
🇳🇴Grålum, Norway
Universitätsklinikum Salzburg, 3.Medizin/Onkologie
🇦🇹Salzburg, Austria
Universitair Ziekenhuis Antwerpen - Hematologie
🇧🇪Edegem, Belgium
University Multiprofile Hospital for Active Treatment 'Sv. Ivan Rilski' EAD, Clinic of Clinical Hematology, Department of Clinical Hematology
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment - Dr Georgi Stranski EAD, Pleven, Clinic of Clinical Haematology
🇧🇬Pleven, Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases EAD, Sofia, Clinic of Clinical Haematology
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment 'Sveta Marina' EAD, Varna, Clinic of Clinical Haematology
🇧🇬Varna, Bulgaria
Szabolcs-Szatmár- Bereg Megyei Kórházak és Egyetemi Oktatókórház, Jósa András Oktatókórház
🇭🇺Nyíregyháza, Hungary
Clinical Centre of Vojvodina, Clinic for Hematology
🇷🇸Novi Sad, Serbia
Kyiv City Clinical Hospital №9, hematology department №1
🇺🇦Kyiv, Ukraine
Versiti Wisconsin, Inc.
🇺🇸Milwaukee, Wisconsin, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Montefiore Medical Center
🇺🇸Bronx, New York, United States