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)

Sanofi

Status and phase: Enrolling; Phase 3

Conditions: Chronic Graft Versus Host Disease

Treatments: Drug: Prednisone; Drug: Prednisolone; Drug: Placebo; Drug: Belumosudil

Study type: Interventional

Funder types: Industry

Identifiers

NCT06143891

2023-505394-32 (Registry Identifier)

EFC17757

U1111-1280-4918 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

Up to 5 years

Enrollment: 260 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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260 participants in 2 patient groups, including a placebo group

Belumosudil

Experimental group

Description:

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)

Treatment:

Drug: Belumosudil

Drug: Prednisolone

Drug: Prednisone

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Prednisolone

Drug: Prednisone