Clinical trial NCT06143891: 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.
Official title: A Randomized, Double-blind, Multicenter, Phase 3 Study to Evaluate Efficacy and Safety of Belumosudil in Combination With Corticosteroids Versus Placebo in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease (cGVHD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Graft Versus Host Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-11-22
Enrollment: 260
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Up to 5 years

Eligibility criteria: 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

Primary outcomes:
measure: Event-Free Survival (EFS)
timeFrame: Until the end of the study (up to 5 years since first patient in).
Secondary outcomes:
measure: Modified Lee Symptom Scale (mLSS)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Durable overall response rate
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Rate of corticosteroid withdrawal
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Overall response rate (ORR)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: ORR by 24 weeks
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Duration of response (DOR)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Dose reduction in corticosteroid
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Failure Free Survival (FFS)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Change in patient reported outcome (PRO)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Overall survival
timeFrame: Until the end of the study (up to 5 years since first patient in).
measure: Time to response (TTR)
timeFrame: Until the end of study (up to 5 years since first patient in)
measure: Response by organ
timeFrame: Until the end of study (up to 5 years since first patient in)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences-Site Number : 8400019
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center- Site Number : 8400001
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Parnassus Heights- Site Number : 8400035
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando- Site Number : 8400023
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine - Atlanta- Site Number : 8400020
state: Georgia
city: Chicago
country: United States
facility: Northwestern University- Site Number : 8400017
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital- Site Number : 8400006
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center- Site Number : 8400024
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital- Site Number : 8400033
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute Site Number : 8400005
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute - Detroit- Site Number : 8400013
state: Michigan
city: Chapel Hill
country: United States
facility: UNC Children's Hospital- Site Number : 8400025
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center - Winston-Salem - Medical Center Boulevard- Site Number : 8400007
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care - Kenwood- Site Number : 8400030
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute- Site Number : 8400026
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University- Site Number : 8400027
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center- Site Number : 8400008
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Site Number : 8400003
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center- Site Number : 8400002
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas - Worth Street- Site Number : 8400010
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute - Methodist Hospital- Site Number : 8400037
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center-Site Number : 8400031
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center- Site Number : 8400004
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center-Site Number : 8400029
state: Wisconsin
city: Pilar
country: Argentina
facility: Investigational Site Number : 0320006
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320005
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Córdoba
country: Argentina
facility: Investigational Site Number : 0320004
city: Westmead
country: Australia
facility: Investigational Site Number : 0360005
state: New South Wales
city: Brisbane
country: Australia
facility: Investigational Site Number : 0360003
state: Queensland
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: Murdoch
country: Australia
facility: Investigational Site Number : 0360004
state: Western Australia
city: Graz
country: Austria
facility: Investigational Site Number : 0400003
city: Linz
country: Austria
facility: Investigational Site Number : 0400001
city: Wien
country: Austria
facility: Investigational Site Number : 0400004
city: Woluwe
country: Belgium
facility: Cliniques Universitaires St. Luc-Investigational Site Number : 0560005
state: Brussels
city: Leuven
country: Belgium
facility: UZ Leuven-Investigational Site Number : 0560001
state: Vlaams-Brabant
city: Bruges
country: Belgium
facility: Investigational Site Number : 0560006
city: Gent
country: Belgium
facility: UZ Gent-Investigational Site Number : 0560003
city: Liège
country: Belgium
facility: CHU de Liège-Investigational Site Number : 0560004
city: Roeselare
country: Belgium
facility: AZ Delta-Investigational Site Number : 0560002
city: Curitiba
country: Brazil
facility: Hospital de Clinicas da Universidade Federal do Parana- Site Number : 0760008
state: Paraná
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760006
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: INCA - Hospital do Câncer - Rio de Janeiro - Praça Da Cruz Vermelha- Site Number : 0760007
city: São Paulo
country: Brazil
facility: Hospital das Clinicas FMUSP- Site Number : 0760004
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein- Site Number : 0760003
city: Calgary
country: Canada
facility: Investigational Site Number : 1240007
state: Alberta
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Maisonneuve Rosemont-Investigational Site Number : 1240001
state: Quebec
city: Montreal
country: Canada
facility: CHU Sainte-Justine-Site Number : 1240003
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Saskatoon
country: Canada
facility: Investigational Site Number : 1240008
state: Saskatchewan
city: Beijing
country: China
facility: Investigational Site Number : 1560019
city: Changchun
country: China
facility: Investigational Site Number : 1560012
city: Changsha
country: China
facility: Investigational Site Number : 1560010
city: Fuzhou
country: China
facility: Investigational Site Number : 1560011
city: Guangzhou
country: China
facility: Investigational Site Number : 1560005
city: Hangzhou
country: China
facility: Investigational Site Number : 1560002
city: Hefei
country: China
facility: Investigational Site Number : 1560014
city: Jinan
country: China
facility: Investigational Site Number : 1560008
city: Jinan
country: China
facility: Investigational Site Number : 1560007
city: Suzhou
country: China
facility: Investigational Site Number : 1560001
city: Suzhou
country: China
facility: Investigational Site Number : 1560006
city: Tianjin
country: China
facility: Investigational Site Number : 1560003
city: Tianjin
country: China
facility: Investigational Site Number : 1560004
city: Wuhan
country: China
facility: Investigational Site Number : 1560013
city: Wuhan
country: China
facility: Investigational Site Number : 1560015
city: Zhengzhou
country: China
facility: Investigational Site Number : 1560009
city: Brno
country: Czechia
facility: Interni hematologicka a onkologicka klinika Fakultni nemocnice Brno-Site Number : 2030003
city: Hradec Kralove
country: Czechia
facility: IV. Interni hematologicka klinika, Fakultni nemocnice Hradec Kralove-Site Number : 2030002
city: Ostrava
country: Czechia
facility: Klinika hematoonkologie, Fakultni nemocnice Ostrava-Site Number : 2030001
city: Praha
country: Czechia
facility: Ustav hematologie a krevni transfuze-Site Number : 2030004
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen University Hospital-Investigational Site Number : 2080002
state: Capital
city: Odense
country: Denmark
facility: Odense University Hospital-Investigational Site Number : 2080003
state: Funen
city: Aarhus
country: Denmark
facility: Department of hematology-Investigational Site Number : 2080001
state: Jutland
city: Marseille
country: France
facility: Institut Paoli Calmettes-Investigational Site Number : 2500004
city: Nantes
country: France
facility: CHU Hotel Dieu-Investigational Site Number : 2500005
city: Paris
country: France
facility: Investigational Site Number : 2500003
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Pessac
country: France
facility: CHU Bordeaux-Hôpital Haut-Lévêque-Investigational Site Number : 2500002
city: Pierre Benite
country: France
facility: Hôpital Lyon Sud-Investigational Site Number : 2500007
city: Rennes
country: France
facility: Hôpital Pontchaillou - CHU de Rennes-Investigational Site Number : 2500008
city: Vandœuvre-lès-nancy
country: France
facility: Investigational Site Number : 2500006
city: Berlin
country: Germany
facility: Investigational Site Number : 2760007
city: Cologne
country: Germany
facility: Investigational Site Number : 2760003
city: Dresden
country: Germany
facility: Investigational Site Number : 2760001
city: Freiburg
country: Germany
facility: Investigational Site Number : 2760005
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760002
city: Kiel
country: Germany
facility: Investigational Site Number : 2760010
city: Münster
country: Germany
facility: Investigational Site Number : 2760009
city: Regensburg
country: Germany
facility: Investigational Site Number : 2760006
city: Tübingen
country: Germany
facility: Investigational Site Number : 2760008
city: Athens
country: Greece
facility: Nosokomeio Paidon I Agia Sofia-Site Number : 3000002
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "George Papanikolaou"-Site Number : 3000001
city: Pok Fu Lam
country: Hong Kong
facility: Investigational Site Number : 3440001
city: Haifa
country: Israel
facility: Investigational Site Number : 3760002
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760005
city: Petah Tikva
country: Israel
facility: Investigational Site Number : 3760006
city: Ramat Gan
country: Israel
facility: Investigational Site Number : 3760003
city: Ramat Gan
country: Israel
facility: Investigational Site Number : 3760004
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760001
city: Torette
country: Italy
facility: Investigational Site Number : 3800012
state: Ancona
city: Genoa
country: Italy
facility: Investigational Site Number : 3800005
state: Genova
city: Milan
country: Italy
facility: Investigational Site Number : 3800009
state: Milano
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800002
state: Milano
city: Rome
country: Italy
facility: Investigational Site Number : 3800001
state: Roma
city: Turin
country: Italy
facility: Investigational Site Number : 3800007
state: Torino
city: Bergamo
country: Italy
facility: Investigational Site Number : 3800003
city: Bologna
country: Italy
facility: Investigational Site Number : 3800004
city: Pavia
country: Italy
facility: Investigational Site Number : 3800011
city: Perugia
country: Italy
facility: Investigational Site Number : 3800010
city: Reggio Calabria
country: Italy
facility: Investigational Site Number : 3800006
city: Udine
country: Italy
facility: Investigational Site Number : 3800008
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medisch Centrum-Site Number : 5280005
city: Groningen
country: Netherlands
facility: Investigational Site Number : 5280003
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280001
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160001
state: Pomorskie
city: Szczecin
country: Poland
facility: Investigational Site Number : 6160008
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200003
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200002
city: Santander
country: Spain
facility: Investigational Site Number : 7240011
state: Cantabria
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240005
state: Catalunya [Cataluña]
city: Barcelona
country: Spain
facility: ICO Institut Català d'Oncologia-Site Number : 7240006
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240004
city: Madrid
country: Spain
facility: Hospital Niño Jesús-Site Number : 7240002
city: Málaga
country: Spain
facility: Hospital Regional Universitarioa de Malaga-Site Number : 7240003
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca-Site Number : 7240007
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío.-Site Number : 7240008
city: Valencia
country: Spain
facility: Investigational Site Number : 7240012
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe-Site Number : 7240001
city: Gothenburg
country: Sweden
facility: Investigational Site Number : 7520003
city: Huddinge
country: Sweden
facility: Investigational Site Number : 7520001
city: Lund
country: Sweden
facility: Investigational Site Number : 7520002
city: Adana
country: Turkey
facility: Investigational Site Number : 7920006
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920002
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920005
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
city: London
country: United Kingdom
facility: Investigational Site Number : 8260002
state: London, City Of
city: Cardiff
country: United Kingdom
facility: Investigational Site Number : 8260006
state: Vale Of Glamorgan, The
city: Leeds
country: United Kingdom
facility: Investigational Site Number : 8260003
city: Manchester
country: United Kingdom
facility: Investigational Site Number : 8260001
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number : 8260004
Study officials:
References: