Belumosudil + Corticosteroids for Chronic Graft Versus Host Disease

(ROCKnrol-1 Trial)

Not currently recruiting at 258 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Corticosteroids

Must not be taking: Belumosudil

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with moderate to severe chronic graft versus host disease (cGVHD), a condition that can occur after a stem cell transplant. The study compares the effects of the drug belumosudil (also known as Rezurock, Rholistiq, KD025, or SLx-2119) with a placebo to determine its effectiveness in managing symptoms when combined with standard corticosteroids. Participants should have recently been diagnosed with cGVHD following a stem cell transplant and should not have received systemic treatments for this condition. The trial aims to find better ways to control cGVHD and improve patients' quality of life. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on other immunosuppressive agents for acute GVHD, the dose must be below a certain level. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that belumosudil is generally well-tolerated by people with chronic graft-versus-host disease (cGVHD). Studies have found that patients taking belumosudil did not experience severe or unexpected side effects. The treatment is considered safe for long-term use, with some patients experiencing long-lasting positive responses.

In earlier studies, most people tolerated the drug well, even those also taking other medications that weaken the immune system. No reports of serious side effects raised concerns about its safety. This suggests that belumosudil could be a safe option for those seeking new treatments for cGVHD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic GVHD?

Researchers are excited about belumosudil for chronic graft versus host disease (cGVHD) because it offers a unique mechanism of action compared to standard treatments like corticosteroids. While most treatments for cGVHD focus on suppressing the immune response broadly, belumosudil specifically targets the Rho-associated coiled-coil containing protein kinase 2 (ROCK2) pathway. This targeted approach may help modulate the immune system more precisely, potentially reducing side effects and improving outcomes for patients. Additionally, the convenience of oral administration once daily makes it a patient-friendly option.

What evidence suggests that this trial's treatments could be effective for chronic GVHD?

Research has shown that Belumosudil, which participants in this trial may receive, offers promising results for treating chronic graft-versus-host disease (cGVHD). Studies indicate that Belumosudil achieves high success rates in treatment and improves survival outcomes for patients with cGVHD. It outperforms the best available treatments, even for those who have tried other options. Additionally, Belumosudil reduces inflammation and improves symptoms by lowering harmful proteins in the body. These findings suggest that Belumosudil could effectively manage cGVHD symptoms and enhance patient health. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people at least 12 years old with a body weight of ≥40kg who have moderate to severe chronic Graft Versus Host Disease (cGVHD) after an allogeneic HCT. They must need systemic corticosteroid treatment and not have had prior cGVHD treatments, except possibly corticosteroids within the last 7 days. Participants should be able to consent and follow contraception guidelines.

Inclusion Criteria

I have had a stem cell transplant and now have moderate to severe chronic graft-versus-host disease.

I need steroids for chronic graft-versus-host disease.

I have not had any treatment for chronic GVHD.

Exclusion Criteria

Your total bilirubin levels in the blood are higher than the normal range.

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)

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive Belumosudil or placebo in combination with corticosteroids until clinically meaningful cGVHD progression or other discontinuation criteria are met

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including at least 30 days follow-up of adverse events

At least 30 days

Long-term follow-up

Participants are followed until death or study close-out

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Belumosudil
• Placebo
• Prednisolone
• Prednisone

Trial Overview

The study tests Belumosudil combined with corticosteroids against a placebo plus corticosteroids in treating newly diagnosed cGVHD. It's a Phase 3 trial where participants are randomly assigned to one of two groups and treated until their condition progresses or they experience unacceptable side effects.

How Is the Trial Designed?

Group I: Belumosudil Experimental Treatment 3 Interventions

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)

Group II: Placebo Placebo Group 3 Interventions

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

Belumosudil is already approved in United States, Canada for the following indications:

Approved in United States as Rezurock for:

• Chronic graft-versus-host disease (cGVHD) in patients aged 12 years and older after failure of at least two prior lines of systemic therapy

Approved in Canada as Rholistiq for:

• Chronic graft-versus-host disease (cGVHD) in adult and pediatric patients 12 years or older

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

Belumosudil, an oral medication targeting ROCK2, showed a high overall response rate of 74% for the 200 mg daily dose and 77% for the 200 mg twice daily dose in patients with chronic graft-versus-host disease (cGVHD) after multiple prior treatments, indicating its efficacy in this challenging condition.

The treatment was well tolerated, with a median duration of response of 54 weeks and significant symptom reduction in 59% to 62% of subjects, while adverse events were consistent with those expected in cGVHD patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Cutler, C., Lee, SJ., Arai, S., et al.[2022]

Ibrutinib, belumosudil, and ruxolitinib have been recently approved by the FDA as effective treatments for chronic graft-versus-host disease (cGVHD), a serious complication following allogeneic hematopoietic cell transplantation.

These new therapies offer alternative mechanisms of action compared to traditional glucocorticoids, potentially reducing the severe side effects associated with long-term steroid use in cGVHD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three US Food and Drug Administration-approved therapies for chronic GVHD. Zeiser, R., Lee, SJ.[2023]

In a multicenter trial involving 138 patients with chronic graft-versus-host disease, the combination of prednisone and sirolimus showed similar effectiveness to the traditional treatment that includes a calcineurin-inhibitor, with no significant differences in response rates after 6 months or 2 years.

The prednisone/sirolimus treatment resulted in fewer kidney-related side effects and better physical functioning scores compared to the calcineurin-inhibitor group, suggesting it may be a safer and more tolerable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801. Carpenter, PA., Logan, BR., Lee, SJ., et al.[2021]

In a study of 50 patients with oral symptoms of chronic graft-versus-host disease (cGVHD), topical budesonide showed a greater reduction in cGVHD examination scores compared to dexamethasone after one month, indicating it may be more effective for this condition.

Both treatments significantly reduced oral pain severity, but while budesonide had a higher overall treatment response rate (53.8%) compared to dexamethasone (29.2%), the difference was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease. Park, AR., La, HO., Cho, BS., et al.[2019]

In a clinical trial involving 12 patients with chronic oral graft versus host disease (GVHD), budesonide mouthwash demonstrated positive responses in all participants, with 7 achieving 'good' or 'complete' recovery within 3 months.

The treatment showed an early response within 2 to 3 weeks, indicating its potential effectiveness as an alternative therapy for chronic oral GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide: a novel treatment for oral chronic graft versus host disease. Elad, S., Or, R., Garfunkel, AA., et al.[2004]

Belumosudil (REZUROCK™) is a newly approved ROCK inhibitor specifically designed for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior treatments.

The drug has received regulatory approval in the USA and is currently under review in several other countries, with ongoing clinical development for systemic sclerosis, highlighting its potential as a significant therapeutic option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil: First Approval. Blair, HA.[2022]

In a study of 164 patients with chronic graft-v-host disease (GVHD), treatment with prednisone alone resulted in better survival rates and fewer infections compared to the combination of prednisone and azathioprine, particularly in standard-risk patients.

However, patients with thrombocytopenia (low platelet counts) showed poorer outcomes with prednisone alone, indicating that alternative treatment strategies are needed for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Sullivan, KM., Witherspoon, RP., Storb, R., et al.[2021]

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The long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained ...