Belumosudil + Corticosteroids for Chronic Graft Versus Host Disease

(ROCKnrol-1 Trial)

Recruiting in Palo Alto (17 mi)

+224 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Sanofi

Must be taking: Corticosteroids

Must not be taking: Belumosudil

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for people with moderate or severe chronic GVHD. It targets newly diagnosed patients who may not respond well to existing treatments. The goal is to manage or reduce the symptoms of chronic GVHD.

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.

What data supports the effectiveness of the drug Belumosudil for chronic graft versus host disease?

Belumosudil has shown promising results in treating chronic graft-versus-host disease (cGVHD) with a high overall response rate of 74-77% in patients who had previously tried other treatments. It was well tolerated and led to symptom reduction in a significant number of patients. ^{1 2 3 4 5}

What makes the drug Belumosudil unique for treating chronic graft-versus-host disease?

Belumosudil is unique because it is an oral drug that specifically targets and inhibits ROCK2, a protein involved in immune cell regulation, which helps reduce harmful immune responses in chronic graft-versus-host disease. It has shown high response rates and symptom reduction in patients who have not responded to at least two other treatments. ^{1 2 3 6 7}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Belumosudil (Other)
• Placebo (Other)
• Prednisolone (Corticosteroid)
• Prednisone (Corticosteroid)

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.

Participant Groups

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 Canada for the following indications:

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

Findings from Research

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, 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Budesonide: a novel treatment for oral chronic graft versus host disease. [2004]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Belumosudil: First Approval. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. [2022]

4. Italy 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. [2021]

5. United States 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Three US Food and Drug Administration-approved therapies for chronic GVHD. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease. [2019]