Belumosudil for Chronic Renal Rejection

Overseen By Shondra Word

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Immunosuppressants

Must not be taking: High intensity statins

Disqualifiers: Heart disease, Severe liver disease, Malignancies, Infections, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop anticoagulation therapy one week before and after a kidney biopsy. You also need to follow FDA guidelines for contraception while using mycophenolic acid.

How is the drug Belumosudil different from other treatments for chronic renal rejection?

Belumosudil is unique because it targets a specific pathway involved in immune response, potentially offering a novel approach to managing chronic renal rejection. Unlike traditional treatments that may have significant side effects like nephrotoxicity (kidney damage), Belumosudil's mechanism of action could provide a more targeted and potentially safer option. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled trial in de novo kidney transplant patients to determine if the addition of belumosudil (brand name- REZUROCK®) on the background of standard immunosuppression will prevent fibrosis in the kidney transplant. Interstitial expansion is the precursor of interstitial fibrosis and graft loss. The hypothesis underlying the study is that abgrogating the fibrogenic effects of the RhoA pathway with belumosudil will reduce structural damage in transplanted kidneys and possible subsequent transplant failure.

Eligibility Criteria

This trial is for new kidney transplant patients. It's testing if a drug called belumosudil can prevent scarring and damage in the transplanted kidneys, which could lead to graft loss. Participants must be on standard immunosuppression therapy.

Inclusion Criteria

I am getting my first or second kidney transplant, and my first wasn't lost to rejection or disease in the first year.

I agree to follow specific lifestyle guidelines for the study.

I am a woman who can have children and have a negative pregnancy test.

Exclusion Criteria

I have been diagnosed with focal segmental glomerulosclerosis.

My kidney donor is a perfect match or completely different.

I received a kidney transplant with both kidneys from one donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 200mg/day of belumosudil or placebo for 12 months to prevent interstitial fibrosis and tubular atrophy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in eGFR and biomarkers of fibrosis

4-8 weeks

Treatment Details

Interventions

• Belumosudil

Trial Overview The study compares two groups: one taking the drug belumosudil (200 mg daily) and another taking a placebo, with both groups also receiving standard care post-transplant. The goal is to see if belumosudil reduces kidney scarring.

Participant Groups

Group I: Belumosudil Experimental Treatment 1 Intervention

200mg/day belumosudil for 12 months

Group II: Placebo Placebo Group 1 Intervention

Daily placebo for 12 months

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

In a proof-of-concept study involving 12 kidney transplant recipients, a regimen combining belatacept, mycophenolic acid, steroids, and rabbit anti-thymocyte globulin significantly reduced acute rejection rates, with only 2 out of 12 patients experiencing rejection.

The study demonstrated that this treatment approach was safe, as no patients developed serious complications like post-transplant lymphoproliferative disorder, and all patients maintained their grafts without any deaths during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study. Cicora, F., Mos, F., Petroni, J., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Belatacept prophylaxis against organ rejection in adult kidney-transplant recipients. [2016]

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

Novel immunosuppressive agents in kidney transplantation. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study. [2015]

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

Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept. [2021]

5. Canada pubmed.ncbi.nlm.nih.gov

Ten years experience with belatacept-based immunosuppression after kidney transplantation. [2021]