Belumosudil for Lung Transplant Rejection

(ROCKaspire Trial)

Recruiting at 137 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Azithromycin

Disqualifiers: Lung function decline, 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: 26

Duration: 26 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment, belumosudil, for individuals experiencing lung transplant rejection. The study compares belumosudil to a placebo, both administered alongside azithromycin and other standard treatments, to determine if it benefits those whose lung function continues to decline despite azithromycin use. It targets individuals who had a lung transplant over a year ago and still face lung issues despite current treatment. Those who have undergone a bilateral lung transplant and experience reduced lung function may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to access a potentially effective treatment early.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants will continue their standard-of-care immunosuppression and azithromycin therapy during the study.

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

Past studies have shown belumosudil to be safe. Research on this treatment for various conditions suggests that most patients tolerate it well. Data from earlier clinical trials revealed no unexpected safety issues. Common side effects included tiredness, nausea, and diarrhea, but these were usually mild.

Additionally, the FDA has already approved belumosudil for another condition, supporting its known safety. This approval indicates thorough testing and monitoring. While no treatment is entirely free of side effects, available data suggest that belumosudil is generally safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung transplant rejection?

Belumosudil is unique because it targets an entirely different mechanism than typical treatments for lung transplant rejection, such as immunosuppressants. Most treatments aim to broadly suppress the immune system to prevent rejection, but Belumosudil specifically inhibits the Rho-associated coiled-coil containing protein kinase 2 (ROCK2) pathway. This targeted action could mean fewer side effects and improved outcomes by directly modulating the immune response. Researchers are excited about Belumosudil because it offers a more precise approach, potentially leading to better transplant longevity and quality of life for patients.

What evidence suggests that belumosudil might be an effective treatment for lung transplant rejection?

Research has shown that belumosudil, one of the treatments studied in this trial, may help treat chronic graft-versus-host disease (cGVHD), which resembles lung transplant rejection. It works by targeting parts of the immune system that cause inflammation and damage. In studies on cGVHD, belumosudil improved symptoms and led to better patient outcomes. This trial will test belumosudil with azithromycin to determine if it can also manage chronic lung allograft dysfunction (CLAD) by reducing harmful immune responses. Although belumosudil is not yet proven for lung transplant rejection, its success with similar conditions is promising. Participants in another arm of this trial will receive a placebo with azithromycin for comparison. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

Adults over 18 who've had a bilateral lung transplant at least a year ago and are experiencing chronic rejection despite taking azithromycin can join. They should have been on azithromycin for at least 8 weeks.

Inclusion Criteria

I have been taking azithromycin for at least 8 weeks.

I have been diagnosed with chronic lung allograft dysfunction.

I had a lung transplant more than a year ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either belumosudil or placebo on top of azithromycin and standard-of-care regimen of immunosuppression

26 weeks

Up to 10 visits

Open-label extension

Participants may continue treatment with belumosudil in an open-label extension

26 weeks

Up to 16 visits

Long-term open-label extension

Participants who enter the long-term OLE will continue treatment with visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin
• Belumosudil
• Placebo

Trial Overview The trial is testing the effectiveness of Belumosudil tablets against a placebo, in addition to standard immunosuppression and azithromycin therapy, for treating lung transplant rejection. It's randomized and double-blind, meaning neither participants nor researchers know who gets the real drug or placebo.

How Is the Trial Designed?

Group I: Belumosudil + Azithromycin Experimental Treatment 2 Interventions

Participants will receive 200 mg belumosudil orally once daily

Group II: Placebo + Azithromycin Placebo Group 2 Interventions

Participants will receive placebo orally once daily

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

Current lung transplant immunosuppression typically relies on a combination of a calcineurin inhibitor, an antimetabolite, and corticosteroids, which remains the standard despite the introduction of newer agents.

Recent evidence indicates that while newer regimens with tacrolimus and mycophenolate are being adopted, they do not reduce the risk of chronic allograft rejection (bronchiolitis obliterans syndrome) compared to traditional therapies, and antibody-based induction therapies have not shown a survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for immunosuppression in lung transplantation. Hopkins, PM., McNeil, K.[2021]

New biological immunosuppressants, including monoclonal antibodies targeting specific T cell molecules and interleukin receptors, show promise in preventing transplant rejection by effectively modulating the immune response.

Several novel drugs, such as FK 506 and rapamycin, have been identified as effective immunosuppressants, each working through different mechanisms like inhibiting lymphokine production or blocking signal transduction, which are crucial for lymphocyte activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New immunosuppressive therapies in kidney transplantation]. Pomer, S.[2021]

The review covers the immunosuppressive effects and mechanisms of action of novel drugs like tacrolimus, sirolimus, mycophenolic acid, and leflunomide, highlighting their potential in managing immune responses.

It also discusses innovative strategies for using conventional immunosuppressants, such as methotrexate and aerosolized immunosuppression, which may enhance treatment outcomes for patients experiencing recurrent rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of immunosuppression for lung transplantation. Novel drugs, new uses for conventional immunosuppressants, and alternative strategies. Hausen, B., Morris, RE.[2019]

Lung transplantation has a survival rate of less than 50% after 5 years, primarily due to complications like infection and obliterative bronchiolitis, highlighting the urgent need for improved immunosuppressive therapies.

The article reviews promising new immunosuppressive agents, including monoclonal antibodies and novel compounds like cyclosporine microemulsion and tacrolimus, and suggests a potential new regimen to enhance long-term survival in lung transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New immunosuppressive regimens in lung transplantation. Briffa, N., Morris, RE.[2021]

Recent advances in understanding the mechanisms of four key immunosuppressive drugs—tacrolimus, sirolimus, mycophenolate mofetil, and leflunomide—have highlighted their distinct actions at molecular and atomic levels.

Clinical trials have shown that these drugs are highly effective in preventing graft rejection and treating autoimmune diseases, confirming their importance in regulating immune cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Brazelton, TR., Morris, RE.[2019]

In a study involving 20 lung transplant patients, the use of alemtuzumab induction with reduced maintenance immunosuppression showed comparable patient and graft survival rates to standard high-dose immunosuppression, with no significant differences at 6 and 12 months.

The rates of acute rejection and infections were similar between the alemtuzumab group and the control group, suggesting that this approach may effectively maintain safety while potentially reducing the toxicity associated with traditional immunosuppressive regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes using alemtuzumab induction in lung transplantation. van Loenhout, KC., Groves, SC., Galazka, M., et al.[2017]

The anti-T cell receptor R73 monoclonal antibody combined with the drug brequinar significantly prolonged the survival of small bowel allografts in a study with Lewis recipients, increasing mean survival from 10.6 days to 83.8 days with optimal dosing.

A triple-drug regimen using lower doses of brequinar, cyclosporine, and sirolimus also achieved indefinite survival of small bowel allografts, indicating that effective immunosuppression can be maintained even with subtherapeutic doses, promoting transplantation tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effect of graft perfusion with anti-T cell receptor monoclonal antibodies on survival of small bowel allografts in rat recipients treated with brequinar alone or in combination with cyclosporine and sirolimus. Wang, M., Qu, X., Stepkowski, SM., et al.[2019]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604459/

Clinical Review - Belumosudil (Rezurock) - NCBI Bookshelf It is likely that there were differences in outcome definitions and assessment time points between the belumosudil studies and the claims data. The sponsor ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20564623

A Study to Test How Effective Belumosudil Tablets Are for ... A Study to Test How Effective Belumosudil Tablets Are for Treating Adult Participants With Chronic Lung Allograft Dysfunction (ROCKaspire).

3. news.sanofi.us news.sanofi.us/2022-04-21-Rezurock-R-belumosudil-patient-reported-outcomes-correlated-with-clinical-response-in-chronic-graft-versus-host-disease

Rezurock® (belumosudil) patient-reported outcomes ... Results from a pooled analysis of Rezurock® (belumosudil) for the treatment of chronic graft-versus-host disease (cGVHD) show certain organ ...

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

Analysis of Long-Term Results from the KD025-208 and ... The median TTNT was 22.1 months (range, 15.2 to 40.3 months), where 47% of patients received a new systemic therapy for cGVHD by 36 months. When compared with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06476132

NCT06476132 | Belumosudil to Block Chronic Lung ... The purpose of this study is to see if taking the study drug, Belumosudil, for 52 weeks in addition to your usual care and medication, will prevent Chronic ...

6. rezurockhcp.com rezurockhcp.com/rezurock-safety-data

Safety Data - REZUROCK® (belumosudil) The safety and tolerability data for REZUROCK are based on results from a pooled analysis of 2 open-label clinical trials.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11971036/

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in ... In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725011595

Analysis of Long-Term Results from the KD025-208 and ... Based on previously published safety data from the primary KD025-208 and ROCKstar publications, there were no new safety concerns observed [8,9]. Overall ...

9. rezurock.com rezurock.com/chronic-gvhd

Clinical Studies & Side Effects Know how REZUROCK® (belumosudil) may help different types of people with cGVHD. Learn about its side effects. See Important Safety Information.