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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of an oral medication called belumosudil for individuals with chronic graft-versus-host disease (cGVHD). This condition can occur after a stem cell or bone marrow transplant when donor cells attack the recipient's body. The trial seeks participants who are Black, African American, American Indian, Alaska Native, Native Hawaiian, or Pacific Islander and have tried at least two different treatments for their cGVHD without success. Participants should have ongoing cGVHD symptoms and be on a stable dose of glucocorticoids (a type of steroid medication). As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that belumosudil is likely to be safe for humans?

Research shows that belumosudil is generally well-tolerated. In previous studies, patients with chronic graft-versus-host disease (cGVHD) experienced positive results with few serious side effects. Evidence indicates that belumosudil was effective and safe, even for those who had many prior treatments. While side effects can occur, they are usually manageable and not severe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic graft-versus-host disease (GVHD), which often include steroids and immunosuppressive drugs, belumosudil offers a novel approach by targeting the ROCK2 signaling pathway. This unique mechanism of action helps regulate immune responses and inflammation, potentially improving outcomes for patients who don't respond well to existing therapies. Researchers are excited about belumosudil because it provides a more targeted treatment option that could lead to better control of symptoms and reduce the long-term side effects associated with traditional immunosuppressive therapies.

What evidence suggests that belumosudil might be an effective treatment for chronic graft-versus-host disease?

Research has shown that Belumosudil, which participants in this trial will receive, effectively treats chronic graft-versus-host disease (cGVHD). In one study, 90% of patients responded positively to the treatment. Belumosudil blocks a protein called ROCK2, involved in inflammation and tissue damage, helping to reduce symptoms. The FDA has approved it for patients with cGVHD who have not had success with other treatments. The treatment is generally well-tolerated, and patients have experienced long-lasting benefits. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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, 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]

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 (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 (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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40318736/

Belumosudil for Chronic Graft-Versus-Host Disease - PubMed This pooled analysis reports the long-term follow-up (overall median follow-up duration of 31.4 months) results from these studies in patients ...

2. astctjournal.org astctjournal.org/article/S2666-6367(25)01159-5/fulltext

Analysis of Long-Term Results from the KD025-208 and ... Durability of response was shown through an increase in DOR, FFS, and TTNT. •. Belumosudil was well tolerated in patients with cGVHD after long-term follow-up.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3479/537087/Belumosudil-reduces-oral-chronic-graft-versus-host

Belumosudil reduces oral chronic graft-versus-host disease ... In a murine model of induced liver fibrosis, belumosudil was effective in reducing liver fibrosis through direct and indirect effects on ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41087183/

[Effectiveness and safety of belumosudil in 20 patients with ... All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8 ...

5. nature.com nature.com/articles/s41409-024-02507-9

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in ... Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD).

6. astctjournal.org astctjournal.org/article/S2666-6367(25)01520-9/fulltext

Efficacy And Safety Of Belumosudil In The Treatment ... Efficacy And Safety Of Belumosudil In The Treatment Of Refractory Chronic Graft-Versus-Host Disease: A Systematic Review And Meta-analysis.

7. nature.com nature.com/articles/s41409-025-02554-w

Efficacy and safety of belumosudil for treatment of cGVHD Median failure-free survival (FFS) was not reached, with 6- and 12-month FFS rates of 89.1% and 80.4%, respectively. Nine patients died, mainly ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02841995

NCT02841995 | A Study to Evaluate the Safety, Tolerability ... This study was been conducted to evaluate the safety, tolerability, and activity of belumosudil (formerly known as KD025) in adult participants with chronic ...

9. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7332/528161/Effectiveness-and-Safety-of-Belumosudil-in-Heavily

Effectiveness and Safety of Belumosudil in Heavily-Treated ... In this real-world study, belumosudil showed rapid, meaningful response with acceptable tolerability in a group of patients with heavily pretreated severe ...