A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.
Phase 3 – large-scale trial before approval
Conditions:
Chronic Graft Versus Host Disease
Sponsor: Sanofi
trial.available_in:
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Overview
This is a parallel, Phase 3, two-arm study for the treatment of newly diagnosed moderate or severe chronic GVHD.
The study duration for a participant includes up to 4 weeks for screening; a treatment period until clinically meaningful cGVHD progression (defined as progression requiring addition of new systemic treatment for cGVHD), relapse/recurrence of the underlying disease, participant starts new systemic treatment for cGVHD or experiences an unacceptable toxicity, at the request of the participants or the investigators, or until the end of study is reached, whichever comes first; at least 30 days follow-up of adverse events (AEs) after the last dose until resolution or stabilization, if applicable; and long-term follow-up until death or study close-out, whichever comes first.
Description
Up to 2.5 years
Who can participate
Inclusion Criteria:
* Patients must be at least 12 years of age inclusive, at the time of signing the informed consent
* Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014)
* Participants who require systemic treatment with corticosteroids for cGVHD
* Participants who have not received any prior systemic treatment for cGVHD (including ECP)
* If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol
* For adult participants, the body weight should be ≥40 kg. For adolescent participants, the body weight should be ≥30 kg
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Participants or their legally authorized representative must be capable of giving signed informed consent
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
* Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of progressive or relapsed underlying disease after the most recent allogeneic HCT
* Post-transplant lymphoproliferative disease within 4 weeks prior to randomization
* Female participants who are pregnant or breastfeeding
* Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day Prior/concomitant therapy
* Participant has had previous exposure to belumosudil.
* Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant.
Prior/concurrent clinical study experience
* Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer Diagnostic assessments
* Karnofsky (if aged ≥16 years)/Lansky (if aged \<16 years) Performance Score of \< 60
* Platelets \<25 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
* Absolute neutrophil count (ANC) \<0.5 x 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening
* Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged \<18 years)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>3 x ULN without liver cGVHD or\>5 × ULN with liver) cGVHD
* Total bilirubin \>1.5 × (ULN) (\>3 × ULN if Gilbert syndrome)
* Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014)
* History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease)
* Known history of human immunodeficiency virus (HIV)
* Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator's judgement
* Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
* Unable to swallow tablets
* Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
* Any active, uncontrolled infections assessed to be clinically significant by the Investigator
Locations
21
Argentina (1)
Investigational Site Number : 0320006
Pilar , Buenos Aires
Australia (1)
Investigational Site Number : 0360005
Westmead , New South Wales
Belgium (1)
Cliniques Universitaires St. Luc-Investigational Site Number : 0560005
Woluwe , Brussels Capital
Brazil (1)
Hospital de Clinicas da Universidade Federal do Parana- Site Number : 0760008
Curitiba , Paraná
Canada (1)
Investigational Site Number : 1240007
Calgary , Alberta
China (1)
Investigational Site Number : 1560019
Beijing
Czech Republic (1)
Interni hematologicka a onkologicka klinika Fakultni nemocnice Brno-Site Number : 2030003
Brno
Denmark (1)
Rigshospitalet Copenhagen University Hospital-Investigational Site Number : 2080002
Copenhagen , Capital
France (1)
Institut Paoli Calmettes-Investigational Site Number : 2500004
Marseille
Greece (1)
Nosokomeio Paidon I Agia Sofia-Site Number : 3000002
Athens
Hong Kong (1)
Investigational Site Number : 3440001
Pok Fu Lam
Israel (1)
Investigational Site Number : 3760002
Haifa
Italy (1)
Investigational Site Number : 3800012
Torette , Ancona
Netherlands (1)
Amsterdam Universitair Medisch Centrum-Site Number : 5280005
Amsterdam
Poland (1)
Investigational Site Number : 6160001
Gdansk , Pomeranian Voivodeship
South Korea (1)
Investigational Site Number : 4100002
Seoul , Seoul-teukbyeolsi
Spain (1)
Investigational Site Number : 7240011
Santander , Cantabria
Sweden (1)
Investigational Site Number : 7520003
Gothenburg
Turkey (1)
Investigational Site Number : 7920006
Adana
United Kingdom (1)
Investigational Site Number : 8260006
Cardiff , Cardiff [Caerdydd Gb-crd]
United States (1)
University of Arkansas for Medical Sciences-Site Number : 8400019