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. (ROCKnrol-1)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Drug: Belumosudil; Drug: Prednisone; Drug: Prednisolone; Drug: Placebo

Detailed Description

Up to 5 years

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Investigational Site Number : 0360005
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Recruiting
      • Investigational Site Number : 0360003
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Investigational Site Number : 0360001
  • Western Australia
    • Murdoch, Western Australia, Australia, 6961
      • Recruiting
      • Investigational Site Number : 0360004
• Belgium
  • Gent, Belgium, 9000
    • Recruiting
    • Investigational Site Number : 0560003
  • Roeselare, Belgium, 8800
    • Recruiting
    • Investigational Site Number : 0560002
  • Sint-Lambrechts-Woluwe, Belgium, 1200
    • Recruiting
    • Investigational Site Number : 0560005
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • Investigational Site Number : 1240001
    • Montreal, Quebec, Canada, H4A3J1
      • Recruiting
      • Investigational Site Number : 1240002
    • Montreal, Quebec, Canada, H3T1C5
      • Recruiting
      • Investigational Site Number : 1240003
• Czechia
  • Hradec Kralove, Czechia, 50005
    • Recruiting
    • Investigational Site Number : 2030002
• Denmark
  • Odense C, Denmark, 5000
    • Recruiting
    • Investigational Site Number : 2080003
• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • Investigational Site Number : 2760002
  • Münster, Germany, 48149
    • Recruiting
    • Investigational Site Number : 2760009
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Investigational Site Number : 3760002
  • Jerusalem, Israel, 91120
    • Recruiting
    • Investigational Site Number : 3760005
  • Petach Tikva, Israel
    • Recruiting
    • Investigational Site Number : 3760006
  • Ramat Gan, Israel, 5266202
    • Recruiting
    • Investigational Site Number : 3760004
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Investigational Site Number : 3760001
  • Tel HaShomer, Israel, 52621
    • Recruiting
    • Investigational Site Number : 3760003
• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • Investigational Site Number : 3800003
  • Bologna, Italy, 40138
    • Recruiting
    • Investigational Site Number : 3800004
  • Genova, Italy, 16132
    • Recruiting
    • Investigational Site Number : 3800005
  • Reggio Calabria, Italy, 89133
    • Recruiting
    • Investigational Site Number : 3800006
  • Roma, Italy, 00168
    • Recruiting
    • Investigational Site Number : 3800001
  • Torino, Italy, 10126
    • Recruiting
    • Investigational Site Number : 3800007
  • Lombardia
    • Rozzano, Lombardia, Italy, 20089
      • Recruiting
      • Investigational Site Number : 3800002
• Spain
  • Málaga, Spain, 29010
    • Recruiting
    • Investigational Site Number : 7240003
  • Salamanca, Spain, 37007
    • Recruiting
    • Investigational Site Number : 7240007
  • Sevilla, Spain, 41013
    • Recruiting
    • Investigational Site Number : 7240008
  • Valencia, Spain, 46026
    • Recruiting
    • Investigational Site Number : 7240001
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Recruiting
      • Investigational Site Number : 7240005
• Sweden
  • Göteborg, Sweden, 413 45
    • Recruiting
    • Investigational Site Number : 7520003
  • Lund, Sweden, 221 85
    • Recruiting
    • Investigational Site Number : 7520002
  • Stockholm, Sweden, 14186
    • Recruiting
    • Investigational Site Number : 7520001
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Investigational Site Number : 8260003
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • Investigational Site Number : 8260001
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Investigational Site Number : 8260004
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Site Number : 8400001
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute-4100 John R St Site Number : 8400013
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Recruiting
      • Oncology Hematology Care Inc Site Number : 8400030
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute at Tennessee Oncology Site Number : 8400003
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • Sarah Cannon Research Institute Site Number : 8400002
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology, PA Site Number : 8400010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belumosudil; Participants will receive belumosudil 200 mg tablets Per os(PO) once daily (QD) per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study note: 200mg two times a day (BID) is used in some cases, when the subject is taking a proton pump inhibitor or a strong CYP3A4 inducer)	Drug: Belumosudil; Pharmaceutical form:Tablet-Route of administration:oral; Other Names: REZUROCK; SAR445761/ KD025; Drug: Prednisone; Pharmaceutical form:Tablet-Route of administration:oral; Drug: Prednisolone; Pharmaceutical form:Tablet-Route of administration:oral
Placebo Comparator: Placebo; Participants will receive matching placebo tablets PO QD per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study	Drug: Prednisone; Pharmaceutical form:Tablet-Route of administration:oral; Drug: Prednisolone; Pharmaceutical form:Tablet-Route of administration:oral; Drug: Placebo; Pharmaceutical form:Table-Route of administration:oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): September 29, 2028
• Study Completion (Estimated): September 29, 2028

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Prednisolone; Prednisone; Belumosudil
• Other Study ID Numbers: EFC17757; 2023-505394-32 (Registry Identifier: CTIS); U1111-1280-4918 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No