Belumosudil for Lung Transplant

(CLAD Trial)

Recruiting at 11 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Calcineurin inhibitors

Must not be taking: Sirolimus, Everolimus

Disqualifiers: Multi-organ transplants, HIV, Hepatitis B, others

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

Duration: 52 weeks

234 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug Belumosudil to determine its effectiveness in preventing Chronic Lung Allograft Dysfunction (CLAD) in lung transplant patients with signs of rejection or inflammation. The study aims to assess whether Belumosudil, when combined with regular medication, can stop or slow lung damage compared to a placebo. Suitable candidates for this trial include lung transplant recipients who recently had a biopsy showing issues like Acute Rejection or Organizing Pneumonia and are experiencing inflammation or rejection signs. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. In fact, it mentions that you will continue your usual care and medication along with the study drug, Belumosudil.

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

Research shows that Belumosudil is generally safe for patients. Previous studies have not identified any new safety issues. For example, long-term studies with patients who have chronic graft-versus-host disease (cGVHD) reported no unexpected side effects. This is reassuring because cGVHD and lung transplant rejection share some similarities. The FDA has already approved Belumosudil for treating cGVHD, indicating its safety has been reviewed for that condition. However, every treatment can have side effects, so staying informed and discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

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

Unlike the standard of care for lung transplant recipients, which typically involves immunosuppressive drugs to prevent organ rejection, Belumosudil offers a unique approach by targeting the ROCK2 pathway. This pathway is associated with immune cell regulation, and Belumosudil is designed to modulate immune responses more precisely. Researchers are excited about this treatment because it could potentially minimize the side effects commonly associated with traditional immunosuppressants while maintaining effective protection against organ rejection. Additionally, Belumosudil's mechanism may offer improved outcomes by addressing specific cellular pathways not targeted by current therapies.

What evidence suggests that Belumosudil might be an effective treatment for CLAD?

In this trial, participants will receive either Belumosudil (Rezurock®) or a placebo, alongside maintenance immunosuppression. Research has shown that Belumosudil yields promising results in treating chronic graft-versus-host disease (cGVHD), which resembles a lung condition called chronic lung allograft dysfunction (CLAD). Studies have found that patients with cGVHD improved when treated with Belumosudil, particularly in the early stages of the disease. This drug blocks a molecule in the body, reducing inflammation and scarring, which are crucial in the development of CLAD. Although Belumosudil is already approved for cGVHD, its potential to prevent CLAD remains under investigation. Early findings suggest that the drug might help lessen lung-related symptoms and improve overall health in patients with lung transplants. ^{4 5 6 7 8}

Who Is on the Research Team?

Scott M. Palmer, M.D., M.H.S.

Principal Investigator

Duke University Medical Center: Transplantation

Are You a Good Fit for This Trial?

This trial is for lung transplant recipients at high risk of developing CLAD, who have had a recent biopsy showing rejection or inflammation. Participants must be on usual care and medication post-transplant. Specific conditions like Acute Rejection, Lymphocytic Bronchiolitis, Organizing Pneumonia, or Acute Lung Injury in the biopsy qualify them.

Inclusion Criteria

Participant and/or parent or guardian must be able to understand the purpose of the study, willing to participate, sign the informed consent, and if applicable assent.

In the absence of contraindications, must have received adult vaccinations or documented immunity as outlined in current National Institute of Allergy and Infectious Diseases (NIAID) Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials

Meeting hematologic laboratory criteria: absolute neutrophil count (ANC) ≥ 0.5 x 10(9)/L and platelet count ≥ 50 x 10(9)/L

Exclusion Criteria

Recipient human immunodeficiency virus (HIV) positive.

Pregnant or breastfeeding

I received a lung transplant from a donor with EBV, but I don't have EBV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Belumosudil or placebo plus maintenance immunosuppression for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-3 years

What Are the Treatments Tested in This Trial?

Interventions

• Belumosudil

Trial Overview The study tests if Belumosudil can prevent Chronic Lung Allograft Dysfunction (CLAD) when taken for 52 weeks alongside standard post-transplant care. It compares the effectiveness of Belumosudil plus maintenance immunosuppression against a placebo with maintenance immunosuppression.

How Is the Trial Designed?

Group I: Belumosudil plus maintenance IS Experimental Treatment 1 Intervention

Eligible lung transplant recipients who experience a qualifying biopsy 60 to 550 days posttransplant will be randomized into the study. 200 mg of Belumosudil (increased to 200 mg twice daily in participants receiving concurrent strong CYP3A inducers or PPIs) + maintenance IS will be administered daily for one year from randomization.

Group II: Placebo + maintenance IS Placebo Group 1 Intervention

Eligible lung transplant recipients who experience a qualifying biopsy 60 to 550 days posttransplant will be randomized into the study. Placebo plus maintenance immunosuppression (IS) will be administered for one year

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?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Monthly treatment with basiliximab (BSX) in lung transplant recipients with chronic renal dysfunction (CRD) led to stabilization of renal function in 78% of patients over 6-12 months, as indicated by an increase in creatinine clearance.

The treatment allowed for a reduction in calcineurin inhibitor (CNI) exposure, which is associated with nephrotoxicity, while maintaining spirometric stability in lung function for some patients, although the presence of chronic lung allograft dysfunction (CLAD) complicated the assessment of BSX's overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Monthly Anti-CD25+ Treatment with Basiliximab on the Progression of Chronic Renal Dysfunction after Lung Transplantation. Ross, DJ., Belperio, J., Natori, C., et al.[2022]

In a retrospective study of 8 lung transplant patients with severe renal insufficiency, the use of belatacept allowed for a safe reduction in nephrotoxic immunosuppressant drugs without causing moderate or severe acute rejection.

Belatacept treatment was associated with stable or improved renal function in most patients, with glomerular filtration rate (GFR) remaining stable in 2 patients and increasing in 5, suggesting it may be a beneficial alternative for managing renal insufficiency in lung transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for renal rescue in lung transplant patients. Timofte, I., Terrin, M., Barr, E., et al.[2022]

In a study involving 11 lung and heart-lung transplant recipients diagnosed with bronchiolitis obliterans syndrome (BOS), switching from calcineurin inhibitor-based immunosuppression to a regimen including sirolimus (Sir) and mycophenolate (MMF) showed mixed results, with some patients experiencing stable graft function and slowed progression of BOS.

Despite the potential benefits, the overall lung function (measured by FEV1) decreased after conversion, indicating that while some patients may benefit, the approach needs further investigation in randomized trials to determine its effectiveness in managing BOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation. Groetzner, J., Wittwer, T., Kaczmarek, I., et al.[2022]

In a study of 11 lung transplant recipients who switched from traditional immunosuppressive regimens to belatacept due to severe side effects, the incidence of acute cellular rejection remained stable, indicating that belatacept may be a safe alternative.

Post-conversion to belatacept, patients showed a significant improvement in kidney function, as measured by estimated glomerular filtration rate, suggesting that belatacept may offer renal benefits without increasing the risk of infections or affecting blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors. Iasella, CJ., Winstead, RJ., Moore, CA., et al.[2022]

Belatacept, an immunosuppressant approved for kidney transplants, was used in a lung transplant recipient who had complications from other medications, but its safety and efficacy in lung transplantation are still not established.

The patient did not experience cellular rejection while on belatacept, but he did face complications like anemia and recurrent pneumonias, highlighting the need for further research on belatacept's use in lung transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for Maintenance Immunosuppression in Lung Transplantation. Hui, C., Kern, R., Wojciechowski, D., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9792394/

Clinical response to belumosudil in bronchiolitis obliterans ... Belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease.

2. 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 ...

3. 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 ...

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. rezurock.com rezurock.com/chronic-gvhd

Clinical Studies & Side Effects REZUROCK has been shown to help many different types of people with chronic GVHD after failure of any 2 other types of treatment.

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

Clinical Review - Belumosudil (Rezurock) - NCBI Bookshelf Efficacy and Safety Results for Naive Indirect Comparison of Belumosudil, Ruxolitinib, and Ibrutinib. Go to: Appendix 2. Summary and Appraisal of Pooled ...

7. 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 ...

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

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.