Belumosudil for Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation

NCT06751602 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 2 other identifiers: PRO00037984U1111-1291-6888
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rejection Chronic Renal

Keywords

kidney transplantation; RhoA/Rock pathway; interstitial fibrosis/tubular atrophy

Outcome Measures

Primary Outcomes (1)

• Difference in Severe Treatment-Emergent Adverse Events within 12 Months

  The difference in the proportion of cumulative treatment-emergent adverse events determined to be ≥ grade 3 severity that occur during 12 months from the first dose of belumosudil compared to the placebo group

  Time of first dose to 12 months after first dose (study drug/placebo)

Secondary Outcomes (1)

• Proportion of Participants Developing IFTA Progression from Baseline

  12 months after first dose (study drug/placebo)

Other Outcomes (10)

• Change in Urinary Albumin-to-Creatinine Ratio

  12 months after first dose of study drug or placebo

• Urinary Albumin-to-Creatinine Ratio

  12 months after first dose of study drug or placebo

• Change in estimated glomerular filtration rate

  12 months after first dose of study drug or placebo

Study Arms (2)

Belumosudil

EXPERIMENTAL

200mg/day belumosudil for 12 months

Drug: Belumosudil 200 mg QD

Placebo

PLACEBO COMPARATOR

Daily placebo for 12 months

Drug: Placebo

Interventions

Belumosudil 200 mg QD DRUG

Belumosudil 200 mcg oral daily

Also known as: Rezurock, Belumosudil

Belumosudil

Placebo DRUG

Placebo (once daily)

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Receiving a first or second kidney, except those whose first kidney transplant was lost during year 1 due to rejection or recurrent disease
• Male or female, aged ≥18 to ≤75
• Women of child bearing potential who have a negative serum pregnancy test prior to treatment
• Women of child bearing potential (including perimenopausal women who have had a menstrual period within the previous 1 year) who agree to use 2 forms of effective birth control regimen (at least one of which is a barrier method) throughout the study period and for 6 weeks following the end of the study or the last dose of mycophenolic acid, whichever comes first.
• Sexually active male patients who agree to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment with mycophenolic acid.
• Panel of reactive antibodies (PRA) \<80% based on the most recent PRA results that are closest to the date of transplant
• Able to take oral medication
• Agreement to adhere to Lifestyle Considerations throughout study duration (refraining from consumption of grapefruit or grapefruit juice; stopping anticoagulation therapy one week prior through one week post-kidney biopsy procedure; agree to follow FDA guidelines regarding contraception while using mycophenolic acid)

You may not qualify if:

• Transplantation of any organ other than kidney
• Living donor kidney recipients having a 6-antigen match with their donor or a 0-antigen mismatch
• Planned use of non-calcineurin inhibitor immunosuppression maintenance therapy (eg, belatacept)
• Patients with primary focal segmental glomerulosclerosis
• Recipients of en-bloc kidneys
• Patients who have received or are expected to receive alemtuzumab
• Presence of any donor-specific antibody observed during the current or historical crossmatch assessment
• Presence of primary (or familial) dyslipidemia
• Presence of an increased QTc interval \> 480 ms on screening ECG, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
• Patients with a history of CABG, cardiac stent placement, or MI within 1 year prior to enrollment
• Patients taking high intensity statin therapy (ie, atorvastatin 40 or 80mg, rosuvastatin 20-40mg)
• Diagnosed with severe liver disease, including abnormal liver enzymes greater than 3 times the upper limit of normal or total bilirubin greater than 1.5 times the upper limit of normal.
• Diagnosed with any past or present malignancies except squamous or basal cell carcinoma of the skin excised prior to randomization.
• Diagnosed with active acute or chronic infection, or febrile illness, including absolute neutrophil count less than 1.5 K/µL that, in the Principal Investigator's opinion, would impact the patient's safety or any assessments of this study
• Diagnosed with a genetic disease that leads to excessive bleeding (eg, hemophilia A or factor VIII deficiency, hemophilia B or factor IX deficiency, and von Willebrand disease), genetic or acquired disease that leads to excessive clotting (eg, anti-phospholipid syndrome, factor V Leiden thrombophilia, factor II mutation), or a medical condition requiring uninterrupted long-term systemic anticoagulation after transplantation, which would interfere with obtaining biopsies.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Chen W, Chen W, Chen S, Uosef A, Ghobrial RM, Kloc M. Fingolimod (FTY720) prevents chronic rejection of rodent cardiac allografts through inhibition of the RhoA pathway. Transpl Immunol. 2021 Apr;65:101347. doi: 10.1016/j.trim.2020.101347. Epub 2020 Oct 24.

  PMID: 33131698 BACKGROUND

• Chen W, Chen S, Chen W, Li XC, Ghobrial RM, Kloc M. Screening RhoA/ROCK inhibitors for the ability to prevent chronic rejection of mouse cardiac allografts. Transpl Immunol. 2018 Oct;50:15-25. doi: 10.1016/j.trim.2018.06.002. Epub 2018 Jun 6.

  PMID: 29885441 BACKGROUND

• Subuddhi A, Uosef A, Zou D, Ubelaker HV, Ghobrial RM, Kloc M. Comparative transcriptome profile of mouse macrophages treated with the RhoA/Rock pathway inhibitors Y27632, Fingolimod (Gilenya), and Rezurock (Belumosudil, SLx-2119). Int Immunopharmacol. 2023 May;118:110017. doi: 10.1016/j.intimp.2023.110017. Epub 2023 Mar 15.

  PMID: 36931169 BACKGROUND

MeSH Terms

Conditions

Pulmonary Fibrosis

Interventions

belumosudil

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Surgery

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: December 30, 2024
• Study Start: September 11, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)