Belumosudil for Chronic Graft-Versus-Host Disease

Recruiting at 12 trial locations

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

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Kadmon, a Sanofi Company

Must be taking: Glucocorticoids

Must not be taking: Ibrutinib, Ruxolitinib

Disqualifiers: Cancer relapse, Severe illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure safety and efficacy of oral belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander male and female participants with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy aged 12 years and above. The duration of participants participation will be up to 4 weeks for screening, treatment until clinically significant progression of disease, and 4 weeks of safety follow-up, and then long-term follow-up every 12 weeks.1 Cycle = 28 days.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you need to be on a stable dose of your current cGVHD treatments for at least 2 weeks before screening. If you are taking ibrutinib or ruxolitinib, you must stop them at least 28 days before joining the trial.

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

Belumosudil has shown effectiveness in treating chronic graft-versus-host disease (cGVHD) with a high overall response rate of 74-77% in patients who had tried at least two other treatments. It was well tolerated and led to symptom reduction in over half of the patients, with many maintaining their response for a year or more. ^{1 2 3 4 5}

Is Belumosudil safe for human use?

Belumosudil has been approved for use in patients with chronic graft-versus-host disease (cGVHD) and has been generally well tolerated in clinical trials. Common side effects include infections, fatigue, nausea, diarrhea, and high blood pressure, and some patients discontinued due to possible drug-related adverse effects. ^{1 4 5 6 7}

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

Belumosudil is unique because it is an oral medication that specifically inhibits ROCK2, a protein involved in immune response, helping to restore balance in the immune system and reduce symptoms in patients who have not responded to at least two other treatments. ^{1 4 5 8 9}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for Black, African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander individuals aged 12+ with chronic Graft Versus Host Disease (cGVHD) who have tried at least two systemic therapies. Participants must be in stable condition with a certain performance score and not on specific treatments like ibrutinib or ruxolitinib recently.

Inclusion Criteria

I have been on a stable dose of glucocorticoid therapy for the last 2 weeks.

I am using two forms of birth control and am not pregnant or breastfeeding.

I have ongoing symptoms from a chronic graft-versus-host disease needing systemic treatment.

Exclusion Criteria

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)

I haven't changed my chronic GVHD treatment in the last 2 weeks.

I am currently on ibrutinib or ruxolitinib, or stopped it at least 28 days ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive oral belumosudil once daily or twice daily until clinically significant progression of disease

Safety Follow-up

Participants are monitored for safety after treatment

4 weeks

Long-term Follow-up

Participants are monitored every 12 weeks for long-term outcomes

Treatment Details

Interventions

• Belumosudil

Trial Overview The study tests the safety and effectiveness of an oral drug called Belumosudil in patients with cGVHD. The treatment period includes up to four weeks of screening, ongoing treatment until disease progression, followed by a safety check-up after four weeks and long-term follow-ups every three months.

Participant Groups

Group I: Belumosudil Experimental Treatment 1 Intervention

Participants will receive belumosudil orally, once daily (QD) or twice daily (BID) if they are taking strong CYP3A4 inducers or proton pump inhibitors.

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?

Kadmon, a Sanofi Company

Lead Sponsor

Trials

14

Recruited

670+

Findings from Research

Belumosudil, a kinase inhibitor, was approved by the FDA for treating chronic GvHD in patients aged 12 and older after failing at least two prior therapies, showing a 75% overall response rate in a study of 65 patients.

While 69% of patients achieved a partial response, the treatment was associated with common side effects such as infections and nausea, indicating the need for further studies to assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. Przepiorka, D., Le, RQ., Ionan, A., et al.[2022]

Belumosudil mesylate is the first and only FDA-approved selective ROCK2 inhibitor 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 shown both safety and efficacy in clinical studies, targeting the dysregulated ROCK pathway that contributes to inflammation and fibrosis in cGvHD, a condition affecting up to 70% of patients after allogeneic hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease. Taylor, B., Cohen, J., Tejeda, J., et al.[2022]

In a study of 37 patients with chronic graft-versus-host disease, the addition of the ROCK2 inhibitor Belumosudil (BEL) significantly increased the concentration-dose (C/D) ratios of sirolimus by 160% and tacrolimus by 113%, indicating that dosage adjustments for these immunosuppressive drugs are necessary when starting BEL.

A notable percentage of patients experienced supratherapeutic levels of sirolimus (57%) and tacrolimus (19%) after initiating BEL, highlighting the potential risk for toxicity and the need for close monitoring and possible dose reductions of 25% for tacrolimus and 25% to 50% for sirolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil Impacts Immunosuppression Pharmacokinetics in Patients with Chronic Graft-versus-Host Disease. Gonzalez, R., Gaskill, E., Padilla, M., et al.[2023]

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]

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]

Sirolimus (SRL) significantly reduces the incidence of grade II-IV acute graft-versus-host disease (GVHD) in patients following allogeneic hematopoietic stem cell transplantation, based on a meta-analysis of 1,673 cases from seven studies.

While SRL-based regimens do not increase the risk of common infections, they are associated with a higher incidence of thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD), indicating potential safety concerns despite their efficacy in preventing GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety. Chen, X., Sun, H., Cassady, K., et al.[2022]

Belumosudil, a new oral medication, showed a 32% overall response rate in treating lung cGVHD (bronchiolitis obliterans syndrome) in 59 patients, with better outcomes in those with less severe disease.

Response rates were significantly higher in patients with lower NIH lung scores at enrollment, indicating that earlier intervention may lead to better treatment results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. DeFilipp, Z., Kim, HT., Yang, Z., et al.[2023]

Belumosudil (BLM) is a ROCK inhibitor approved by the FDA for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior therapies, highlighting its efficacy in a challenging patient population.

BLM received breakthrough therapy designation and orphan drug status, indicating its potential significance in treating rare diseases like cGVHD and systemic sclerosis, and it is currently undergoing further regulatory assessments and clinical trials for additional indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease. Ali, F., Ilyas, A.[2022]

Belumosudil, a selective Rho-associated protein kinase 2 inhibitor, shows promise in treating chronic graft-versus-host disease by restoring immune balance and reducing fibrosis, with no significant adverse events reported during the study.

The pharmacokinetics of belumosudil are significantly affected by other medications, such as itraconazole and rifampicin, indicating that dosage adjustments may be necessary when coadministered with proton pump inhibitors like rabeprazole and omeprazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. Schueller, O., Willson, A., Singh, N., et al.[2022]

References

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

FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease. [2022]

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

Belumosudil Impacts Immunosuppression Pharmacokinetics in Patients with Chronic Graft-versus-Host Disease. [2023]

4. 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]

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

Belumosudil: First Approval. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety. [2022]

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

Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. [2023]

8. France pubmed.ncbi.nlm.nih.gov

Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease. [2022]

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

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. [2022]