Rejection Chronic RenalPhase 2NCT06751602
Belumosudil for Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation
A Phase 2 study testing Belumosudil 200 mg QD in people with Rejection Chronic Renal, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rejection Chronic Renal
- What is being tested?
- Belumosudil 200 mg QD
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2025to 30 Mar 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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
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- 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.
- Patient with platelet count less than 50 K/µL.
- Ever diagnosed with Post-Transplant Lymphoproliferative Disorder (PTLD) if a previous kidney transplant was received
- Use of any investigational drug during the 4 weeks prior to enrolling in this study
- Women of child bearing potential who are breastfeeding
- Women of childbearing potential not practicing reliable methods of contraception. Reliable methods for contraception include surgical sterilization (hysterectomy, bilateral tubal ligation), double-barrier method (such as condom and diaphragm). To be considered as post-menopausal and not of childbearing potential, female participants must have experienced 12 consecutive months of amenorrhea.
- Men who are sexually active but do not practice reliable birth control.
- Known allergic reactions to components of REZUROCK®, specifically belumosudil mesylate, microcrystalline cellulose, hypromellose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide or yellow iron oxide.
- Any participant whose surgeon expects they will not perform a baseline biopsy pre- or post-reperfusion of the transplanted organ
- Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Houston Methodist Research Institute
Houston, Texas, 77030
About this study
Official title: A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Belumosudil for the Abrogation of Interstitial Fibrosis and Tubular Atrophy in de Novo Kidney Transplant Recipients
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.
Read the detailed description
Of the 16,521 adult kidney transplants in 2008, death-censored graft loss occurred in 16% of deceased donor kidneys and 7% of living donor kidneys in the ensuing 5 years and has not largely changed in a decade. A majority of this graft loss is presumed to be from IF/TA, previously termed chronic allograft nephropathy. Various causes of injury to the kidney stimulate inflammatory processes. When the inflammation continues (ie, becomes chronic), changes occur in the kidney structure, specifically in the glomerulus and tubular interstitium which leads to fibrosis and a progressive decline in kidney function.
Interstitial fibrosis and tubular atrophy almost invariably occur together and are present in approximately 45% of early indication kidney biopsies by the first year posttransplant. No risk factors have been identified to predict who will experience IF/TA. Combined, IF/TA contributes to renal graft dysfunction or the decline in kidney function after transplantation and may be a factor in the 20.6% of total grafts lost (including death) by 5 years post-transplant.
Expansion of the interstitial compartment is a major component of IF/TA. Protocol and for-cause biopsies have provided evidence of the worsening of IF/TA with time in kidney transplant recipients and demonstrated a direct relationship between interstitial expansion and renal allograft functional decline and graft failure. Interstitial expansion will be assessed as the overall proportion of cortical tissue area associated with IF/TA.
Previous work has shown that chronic rejection depends on macrophage movement to the graft, which is regulated by actin cytoskeleton controlled by the small GTPase RhoA/Rock pathway. Pharmacologic inhibition or macrophage-specific deletion of RhoA prevents chronic rejection in the rodent cardiac transplantation model, and belumosudil was superior in preventing fibrosis.
Controlling hypertension and prevention and treatment of acute rejection are standard approaches to kidney function preservation in kidney transplant recipients. Additionally, the use of CNI-sparing protocols has been reported with various approaches but data are insufficient to equivocally demonstrate consistently lower IF/TA in the approaches reported to date. Thus, it is important to examine additional approaches for prevention of IF/TA in this population.
This study will test the hypothesis that abrogating the fibrogenic effects of the RhoA pathway with belumosudil would abbrograte IF/TA and that reducing this structural damage in transplanted kidneys would result in improved or preserved kidney function and reduced graft loss.
The purpose of this study is to demonstrate that 200mg/day of belumosudil for 12 months administered to de novo kidney transplant recipients will be safe and to examine the course of IF/TA over a 1-year period by testing the ability of 200mg/day belumosudil for 12 months to abrograte the development of IF/TA in de novo kidney transplant recipients compared to placebo.
- Conditions
- Rejection Chronic Renal
- Being tested
- Belumosudil 200 mg QD, Placebo
- Keywords
- kidney transplantation, RhoA/Rock pathway, interstitial fibrosis/tubular atrophy
- Medical subject headings
- Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belumosudil 200 mg QDDrug
Also called Rezurock, Belumosudil
Belumosudil 200 mcg oral daily
PlaceboDrug
Placebo (once daily)
| Study group | Role | What they receive |
|---|---|---|
| Belumosudil | Experimental | 200mg/day belumosudil for 12 months Receives: Drug: Belumosudil 200 mg QD |
| Placebo | Placebo comparator | Daily placebo for 12 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Time of first dose to 12 months after first dose (study drug/placebo)
Secondary outcomes (1)
Proportion of Participants Developing IFTA Progression from Baseline
The proportion of participants developing progression of interstitial fibrosis/tubular atrophy (IFTA) from baseline assessed on pathology using Banff criteria at 1-year following the first dose of belumosudil or placebo
Measured: 12 months after first dose (study drug/placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2024
- Study start11 Sep 2025
- Primary completionDec 2027 (estimated)
- Study completion30 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rejection Chronic RenalStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Caroline Simon, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06751602
- Sponsor's protocol ID
- PRO00037984
- Other IDs
- U1111-1291-6888
- Status last verified
- Nov 2025
- First submitted
- 20 Dec 2024
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33131698Chen 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.
PubMed 29885441Subuddhi 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.
PubMed 36931169
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Belumosudil for the Abrogation of Interstitial Fibrosis and Tubular Atrophy in de Novo Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT06751602
- Acronym / sponsor ID
- PRO00037984
- Conditions
- Rejection Chronic Renal
- Keywords
- kidney transplantation, RhoA/Rock pathway, interstitial fibrosis/tubular atrophy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- 11 Sep 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- 30 Mar 2028 (estimated)
- First posted
- 30 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Of the 16,521 adult kidney transplants in 2008, death-censored graft loss occurred in 16% of deceased donor kidneys and 7% of living donor kidneys in the ensuing 5 years and has not largely changed in a decade. A majority of this graft loss is presumed to be from IF/TA, previously termed chronic allograft nephropathy. Various causes of injury to the kidney stimulate inflammatory processes. When the inflammation continues (ie, becomes chronic), changes occur in the kidney structure, specifically in the glomerulus and tubular interstitium which leads to fibrosis and a progressive decline in kidney function.
Interstitial fibrosis and tubular atrophy almost invariably occur together and are present in approximately 45% of early indication kidney biopsies by the first year posttransplant. No risk factors have been identified to predict who will experience IF/TA. Combined, IF/TA contributes to renal graft dysfunction or the decline in kidney function after transplantation and may be a factor in the 20.6% of total grafts lost (including death) by 5 years post-transplant.
Expansion of the interstitial compartment is a major component of IF/TA. Protocol and for-cause biopsies have provided evidence of the worsening of IF/TA with time in kidney transplant recipients and demonstrated a direct relationship between interstitial expansion and renal allograft functional decline and graft failure. Interstitial expansion will be assessed as the overall proportion of cortical tissue area associated with IF/TA.
Previous work has shown that chronic rejection depends on macrophage movement to the graft, which is regulated by actin cytoskeleton controlled by the small GTPase RhoA/Rock pathway. Pharmacologic inhibition or macrophage-specific deletion of RhoA prevents chronic rejection in the rodent cardiac transplantation model, and belumosudil was superior in preventing fibrosis.
Controlling hypertension and prevention and treatment of acute rejection are standard approaches to kidney function preservation in kidney transplant recipients. Additionally, the use of CNI-sparing protocols has been reported with various approaches but data are insufficient to equivocally demonstrate consistently lower IF/TA in the approaches reported to date. Thus, it is important to examine additional approaches for prevention of IF/TA in this population.
This study will test the hypothesis that abrogating the fibrogenic effects of the RhoA pathway with belumosudil would abbrograte IF/TA and that reducing this structural damage in transplanted kidneys would result in improved or preserved kidney function and reduced graft loss.
The purpose of this study is to demonstrate that 200mg/day of belumosudil for 12 months administered to de novo kidney transplant recipients will be safe and to examine the course of IF/TA over a 1-year period by testing the ability of 200mg/day belumosudil for 12 months to abrograte the development of IF/TA in de novo kidney transplant recipients compared to placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Belumosudil | Experimental | Drug: Belumosudil 200 mg QD200mg/day belumosudil for 12 months |
| Placebo | Placebo comparator | Drug: PlaceboDaily placebo for 12 months |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belumosudil 200 mg QDAlso: Rezurock, BelumosudilBelumosudil 200 mcg oral daily | Drug | Belumosudil |
| PlaceboPlacebo (once daily) | Drug | Placebo |
Primary outcome
Difference in Severe Treatment-Emergent Adverse Events within 12 Months
Time frame: Time of first dose to 12 months after first dose (study drug/placebo)
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
1 secondary outcome
Proportion of Participants Developing IFTA Progression from Baseline
Time frame: 12 months after first dose (study drug/placebo)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
- Background: PubMed 33131698Chen 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.
- Background: PubMed 29885441Chen 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.
- Background: PubMed 36931169Subuddhi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belumosudil 200 mg QD in people with Rejection Chronic Renal, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Severe Treatment-Emergent Adverse Events within 12 Months (time frame: Time of first dose to 12 months after first dose (study drug/placebo)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06751602, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2025.