Belumosudil for Lung Transplant

(CLAD Trial)

Recruiting at 9 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

Trial Summary

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.

How is the drug Belumosudil unique for lung transplant patients?

Belumosudil is unique because it targets a specific pathway involved in immune response, potentially offering a different mechanism of action compared to traditional immunosuppressive drugs used in lung transplants, which often rely on calcineurin inhibitors that can cause kidney damage. ^{1 2 3 4 5}

What is the purpose of this trial?

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 Lung Allograft Dysfunction (CLAD) in participants who have a lung biopsy that shows evidence of rejection or inflammation to the transplanted lung(s). For this study, biopsies that show evidence of Acute Rejection (AR), Lymphocytic Bronchiolitis (LB), Organizing Pneumonia (OP) or Acute Lung Injury (ALI) are referred to as "Qualifying Biopsies"; patients who had evidence of one or more of these conditions on a recent biopsy are eligible for enrollment in this study. Belumosudil is an investigational drug that blocks a molecule in the body that reduces inflammation and scarring and may play a role in the development and progression of CLAD. Belumosudil is a drug approved by the FDA to treat adults and children 12 years and older with chronic graft-versus-host disease (cGVHD), a condition with some similarities to CLAD. The primary objective it to determine the efficacy of treatment with Belumosudil + maintenance immunosuppression (IS) versus placebo + maintenance IS on preventing the subsequent development of probable or definite CLAD, lung retransplant, or death.

Research Team

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

Principal Investigator

Duke University Medical Center: Transplantation

Eligibility Criteria

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

My biopsy after lung transplant shows signs of rejection or injury.

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

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

Treatment Details

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.

Participant Groups

Group I: Belumosudil plus maintenance IS Experimental Treatment 1 Intervention

Eligible lung transplant recipients who experience a qualifying biopsy 90 to 410 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 90 to 410 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+

Findings from Research

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]

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 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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Belatacept for renal rescue in lung transplant patients. [2022]

2. Iran pubmed.ncbi.nlm.nih.gov

The Effect of Monthly Anti-CD25+ Treatment with Basiliximab on the Progression of Chronic Renal Dysfunction after Lung Transplantation. [2022]

3. United States 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. [2022]

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

Belatacept for Maintenance Immunosuppression in Lung Transplantation. [2018]

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

Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors. [2022]