Belumosudil for Lung Transplant Rejection

(ROCKaspire Trial)

Recruiting at 121 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

Trial Summary

What is the purpose of this trial?

This double-blind, randomized, placebo-controlled, multinational, multicenter, parallel-group, Phase 3, 2-arm, study will investigate the efficacy and safety of belumosudil compared with placebo, both administered on top of azithromycin and standard-of-care regimen of immunosuppression in male or female participants at least 1 year after bilateral lung transplant, who are at least 18 years of age and who have evidence of progressive CLAD despite azithromycin therapy. Study details include: The study duration will be up to 31 weeks for participants not entering the open-label extension (OLE) period and up to 57 weeks for participants entering the OLE period but not the long-term OLE. The treatment duration will be up to 26 weeks for participants not entering the OLE period and up to 52 weeks for participants entering the OLE period but not the long-term OLE. The number of visits will be up to 10 visits for participants not entering the OLE period and up to 16 visits for participants entering the OLE period but not the long-term OLE. For participants who enter the long-term OLE, treatment and study participation will continue with visits every 12 weeks per protocol specifications.

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.

What evidence supports the effectiveness of the drug Belumosudil for lung transplant rejection?

The research highlights the effectiveness of new immunosuppressive drugs like tacrolimus and sirolimus in preventing transplant rejection, suggesting that novel drugs targeting immune responses can be beneficial. Although Belumosudil is not specifically mentioned, its role as an immunosuppressant may offer similar benefits in managing lung transplant rejection. ^{1 2 3 4 5}

How is the drug Belumosudil unique for lung transplant rejection?

Belumosudil is unique because it offers a novel approach to treating lung transplant rejection, potentially differing from traditional immunosuppressive regimens that often include drugs like calcineurin inhibitors and mycophenolate mofetil. While traditional treatments focus on broad immunosuppression, Belumosudil may provide a more targeted mechanism, although specific details about its action in lung transplant rejection are not provided in the available research. ^{1 3 4 6 7}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

Evidence for immunosuppression in lung transplantation. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

[New immunosuppressive therapies in kidney transplantation]. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

New immunosuppressive regimens in lung transplantation. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2019]

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

Early outcomes using alemtuzumab induction in lung transplantation. [2017]