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

Warm Antibody Autoimmune Hemolytic Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03764618
• Other study ID #: C-935788-057
• Status: Completed
• Phase: Phase 3
• Start date: April 24, 2019
• Est. completion date: April 11, 2022

Study information

• Verified date: May 2023
• Source: Rigel Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: April 11, 2022
• Est. primary completion date: April 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• 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.
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital - Cancer Trials Unit	Brisbane	Queensland
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Concord Repatriation General Hospital	Sydney	New South Wales
Austria	Universitätsklinik Innsbruck - Innere Medizin V	Innsbruck
Austria	Universitätsklinikum Salzburg, 3.Medizin/Onkologie	Salzburg
Austria	Hanusch-Krankenhaus	Vienna
Austria	Medizinsche Universität Wien	Wien
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk
Belarus	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk
Belgium	Ziekenhuis Network Antwerp, Stuivenberg	Antwerpen
Belgium	Universitair Ziekenhuis Antwerpen - Hematologie	Edegem
Belgium	AZ Nikolaas	Sint-Niklaas
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 'Alexandrovska' EAD, Clinic of Clinical Haematology	Sofia
Bulgaria	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 'Sveta Marina' EAD, Varna, Clinic of Clinical Haematology	Varna
Canada	Hamilton Health Sciences- McMaster University Medical Centre	Hamilton	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Brno Interni hematologicka a onkologicka klinika	Brno
Czechia	Fakultni nemocnice Ostrava Klinika hematoonkologie	Ostrava
Czechia	Ustav Hematologie a Krevni Transfuze	Praha
Denmark	Aalborg University Hopital	Aalborg
Denmark	Aarhus University Hospital - Dept of Hematology	Aarhus N
Denmark	Herlev and Gentofte Hospital	Herlev
France	CHU Angers	Angers
France	Institut d'hématologie de Basse Normandie, CHU Caen	Caen
France	CHU Estaing - Chirurgie digestive et Médecine interne	Clermont-Ferrand
France	CHU Henri Mondor	Créteil
France	Hôpital Saint Antoine	Paris
France	CHU de Bordeaux - GH Sud- Hôpital Haut Lévêque Service Médecine Interne et Maladies Infectieuses	Pessac
France	CHU Toulouse, IUCT Oncopôle	Toulouse
Georgia	LTD Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	M. Zodelava Hematology Centre, Tbilisi	Tbilisi
Germany	Universitätsklinikum Essen	Essen
Germany	University of Leipzig Medical Center, Medical Department I - Haematology and Cell Therapy, Medical Oncology, Hemophilia	Leipzig
Hungary	Semmelweis Egyetem, Általános Orvostudományi Kar, I.sz. Belgyógyászati Klinika, Haematológiai Osztály,	Budapest
Hungary	Szabolcs-Szatmár- Bereg Megyei Kórházak és Egyetemi Oktatókórház, Jósa András Oktatókórház	Nyíregyháza
Hungary	Pécsi Tudományegyetem, Klinikai Központ, I.számú Belgyógyászati Klinikai, Hematológiai Tanszék	Pécs
Italy	ASST degli Spedali Civili di Brescia, Ematologia UOC	Brescia
Italy	Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico di Milano - UO Ematologia	Milano
Italy	SCDU Ematologia AOU "Maggiore della Carità"	Novara
Italy	Ospedale Maggiore, SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina	Trieste
Italy	ULSS8 Berica Ospedale San Bortolo - Unità Operativa Complessa di Ematologia	Vicenza
Netherlands	Academisch Medisch Centrum	Amsterdam
Norway	Ålesund Hospital	Ålesund
Norway	Haukeland University Hospital	Bergen
Norway	Østfold Hopital	Grålum
Romania	Coltea Clinical Hospital	Bucharest
Romania	Emergency University Hospital Bucharest	Bucharest
Romania	"Prof. Dr. Ion Chiricuta" Institute of Oncology Cluj-Napoca	Cluj-Napoca
Russian Federation	Botkin Moscow City Clinical Hospital	Moscow
Russian Federation	National Research Center for Hematology	Moscow
Russian Federation	State Budgetary Healthcare Institution of Moscow city "City Clinical Hospital No 40 Department of Healthcare of Moscow city"	Moscow
Russian Federation	State Budgetary Healthcare Institution of Novosibirsk Region "City Clinical Hospital ?2"	Novosibirsk
Russian Federation	State Budgetary Healthcare Institution Oncology Dispensary No. 2 of the Ministry of Health of the Krasnodar Territory	Sochi
Russian Federation	Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"	Tomsk
Serbia	University Hospital Medical Center "Bezanijska Kosa", Department of Hematology	Belgrade
Serbia	Clinical Center Nis, Clinic for Hematology	Niš
Serbia	Clinical Centre of Vojvodina, Clinic for Hematology	Novi Sad
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	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
Ukraine	Cherkasy Regional Oncology Dispensary, Hematology Center	Cherkasy
Ukraine	City Clinical Hospital ? 4, Hematology Center	Dnipro
Ukraine	Kyiv City Clinical Hospital ?9, hematology department ?1	Kyiv
United Kingdom	East Kent Haemophilia Centre, Kent and Canterbury Hospital	Canterbury	Kent
United Kingdom	Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	Hammersmith Hospital	London
United Kingdom	The Royal London Hospital, Bart's Health NHS Trust	London
United Kingdom	Sandwell and West Birmingham NHS Trust	West Bromwich
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	John Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Affiliated Oncologists	Chicago Ridge	Illinois
United States	Duke Cancer Network	Clayton	North Carolina
United States	Texas Oncology - Baylor Research Institute	Dallas	Texas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Banner MD Anderson Cancer Center at North Colorado Medical Center	Greeley	Colorado
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Moores UC San Diego Cancer Center	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Southern California	Los Angeles	California
United States	Versiti Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Rutgers - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	American Oncology Network Vista Oncology Division	Olympia	Washington
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Marshfield Clinic Cancer Center - Stevens Point	Stevens Point	Wisconsin
United States	Harbor UCLA - Lundquist Institute	Torrance	California
United States	Arizona Oncology Associates, PC--HOPE Division	Tucson	Arizona
United States	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia
United States	Clear Lake Specialties, Research Dept.	Webster	Texas
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Rigel Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	A Hemoglobin Response by Week 24	Proportion of subjects with a hemoglobin response by Week 24.	24 weeks
Secondary	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
Secondary	Change in Hemoglobin From Baseline to End of Treatment	Change in mean hemoglobin from baseline to end of treatment.	24 weeks
Secondary	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
Secondary	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