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.

Chronic Graft Versus Host Disease Clinical Trial

— ROCKnrol-1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06143891
• Other study ID #: EFC17757
• Secondary ID: 2023-505394-32U1
• Status: Recruiting
• Phase: Phase 3
• Start date: January 23, 2024
• Est. completion date: September 29, 2028

Study information

• Verified date: June 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Up to 5 years

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: September 29, 2028
• Est. primary completion date: September 29, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

• Body weight = 40kg

• 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

• Histological relapse of the underlying disease after 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 <50 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test

• Absolute neutrophil count (ANC) <1.0 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 if due to cGVHD 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

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Belumosudil
Pharmaceutical form:Tablet-Route of administration:oral
• Placebo
Pharmaceutical form:Table-Route of administration:oral
• Prednisone
Pharmaceutical form:Tablet-Route of administration:oral
• Prednisolone
Pharmaceutical form:Tablet-Route of administration:oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Australia	Investigational Site Number : 0360003	Herston	Queensland
Australia	Investigational Site Number : 0360001	Melbourne	Victoria
Australia	Investigational Site Number : 0360004	Murdoch	Western Australia
Australia	Investigational Site Number : 0360005	Westmead	New South Wales
Belgium	Investigational Site Number : 0560003	Gent
Belgium	Investigational Site Number : 0560001	Leuven
Belgium	Investigational Site Number : 0560002	Roeselare
Belgium	Investigational Site Number : 0560005	Sint-Lambrechts-Woluwe
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP Site Number : 0760004	Sao Paulo	São Paulo
Canada	Investigational Site Number : 1240001	Montreal	Quebec
Canada	Investigational Site Number : 1240002	Montreal	Quebec
Canada	Investigational Site Number : 1240003	Montreal	Quebec
Czechia	Investigational Site Number : 2030002	Hradec Kralove
Czechia	Investigational Site Number : 2030001	Ostrava - Poruba
Czechia	Investigational Site Number : 2030004	Praha 2
Denmark	Investigational Site Number : 2080001	Aarhus N
Denmark	Investigational Site Number : 2080002	Copenhagen
Denmark	Investigational Site Number : 2080003	Odense C
Germany	Investigational Site Number : 2760001	Dresden
Germany	Investigational Site Number : 2760002	Hamburg
Germany	Investigational Site Number : 2760003	Köln
Germany	Investigational Site Number : 2760009	Münster
Germany	Investigational Site Number : 2760008	Tübingen
Israel	Investigational Site Number : 3760002	Haifa
Israel	Investigational Site Number : 3760005	Jerusalem
Israel	Investigational Site Number : 3760006	Petach Tikva
Israel	Investigational Site Number : 3760004	Ramat Gan
Israel	Investigational Site Number : 3760001	Tel Aviv
Israel	Investigational Site Number : 3760003	Tel HaShomer
Italy	Investigational Site Number : 3800003	Bergamo
Italy	Investigational Site Number : 3800004	Bologna
Italy	Investigational Site Number : 3800005	Genova
Italy	Investigational Site Number : 3800009	Milano
Italy	Investigational Site Number : 3800006	Reggio Calabria
Italy	Investigational Site Number : 3800001	Roma
Italy	Investigational Site Number : 3800002	Rozzano	Lombardia
Italy	Investigational Site Number : 3800007	Torino
Netherlands	Investigational Site Number : 5280003	Groningen
Spain	Investigational Site Number : 7240005	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240003	Málaga
Spain	Investigational Site Number : 7240007	Salamanca
Spain	Investigational Site Number : 7240008	Sevilla
Spain	Investigational Site Number : 7240001	Valencia
Sweden	Investigational Site Number : 7520003	Göteborg
Sweden	Investigational Site Number : 7520002	Lund
Sweden	Investigational Site Number : 7520001	Stockholm
Turkey	Investigational Site Number : 7920006	Adana
Turkey	Investigational Site Number : 7920001	Ankara
Turkey	Investigational Site Number : 7920002	Ankara
Turkey	Investigational Site Number : 7920004	Ankara
Turkey	Investigational Site Number : 7920005	Istanbul
Turkey	Investigational Site Number : 7920003	Izmir
United Kingdom	Investigational Site Number : 8260003	Leeds
United Kingdom	Investigational Site Number : 8260001	Manchester
United Kingdom	Investigational Site Number : 8260004	Newcastle upon Tyne
United States	Sarah Cannon Research Institute Site Number : 8400002	Austin	Texas
United States	Dana Farber Cancer Institute Site Number : 8400005	Boston	Massachusetts
United States	University of Virginia, Emily Couric Clinical Cancer Center Site Number : 8400031	Charlottesville	Virginia
United States	Robert H. Lurie Comprehensive Cancer Cancer Site Number : 8400017	Chicago	Illinois
United States	Oncology Hematology Care Inc Site Number : 8400030	Cincinnati	Ohio
United States	James Cancer Hospital & Wexner Medical Center at the Ohio State University Comprehensive Cancer Center Site Number : 8400026	Columbus	Ohio
United States	Texas Oncology, PA Site Number : 8400010	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute-4100 John R St Site Number : 8400013	Detroit	Michigan
United States	City of Hope Site Number : 8400001	Duarte	California
United States	University of Wisconsin Carbone Cancer Center Site Number : 8400029	Madison	Wisconsin
United States	Sarah Cannon Research Institute Site Number : 8400003	Nashville	Tennessee
United States	University of Pittsburgh Medical Center - Hillman Cancer Ctr Site Number : 8400008	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Germany,  Israel,  Italy,  Netherlands,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS)	from the date of randomization to the date of any predefined event, whichever occurs first	Until the end of the study (up to 5 years since first patient in).
Secondary	modified Lee Symptom Scale (mLSS)	Proportion of participants who achieve a clinically relevant reduction in mLSS of at least 6 points from baseline (Only in participants at least 18 years of age)	Until the end of the study (up to 5 years since first patient in).
Secondary	overall response rate (ORR)	Proportion of participants who achieve an overall response (PR or CR) as per 2014 NIH consensus response criteria by 48 weeks and maintained the response for a duration of at least 6 months	Until the end of the study (up to 5 years since first patient in).
Secondary	rate of corticosteroid withdrawal	Proportion of participants who successfully discontinue all systemic corticosteroids for cGVHD for at least 30 days before the occurrence of cGVHD progression, or start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or unacceptable toxicity	Until the end of the study (up to 5 years since first patient in).
Secondary	Overall response rate (ORR)	Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHD	Until the end of the study (up to 5 years since first patient in).
Secondary	ORR by 24 weeks	Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria by 24 weeks (Cycle 7 Day 1) before the start of new systemic treatment for cGVHD	Until the end of the study (up to 5 years since first patient in).
Secondary	Duration of response (DOR)	Time from the date of the first response to the date of cGVHD progression as defined by 2014 NIH consensus response criteria, start of new systemic treatment for cGVHD, or death, whichever occurs first. DOR is determined only for participants who achieved overall response (PR or CR) as per 2014 NIH consensus response criteria	Until the end of the study (up to 5 years since first patient in).
Secondary	Dose reduction in corticosteroid	Proportion of participants with a reduction in daily corticosteroid dose	Until the end of the study (up to 5 years since first patient in).
Secondary	Failure Free Survival (FFS)	Failure Free Survival (FFS) is defined as the time from the date of randomization to the date of start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first.	Until the end of the study (up to 5 years since first patient in).
Secondary	Change in patient reported outcome (PRO)	Change from baseline in Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) (Only in participants at least 18 years of age) and the European Quality of Life Group Questionnaire with 5 Dimensions and 5 Levels (EQ5D5L)	Until the end of the study (up to 5 years since first patient in).
Secondary	Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)		Until the end of the study (up to 5 years since first patient in).
Secondary	Overall survival	The time from the date of randomization to the date of death due to any cause	Until the end of the study (up to 5 years since first patient in).