Kidney Transplant RejectionPhase 2/3BELA-M-RNCT06291103
Screening for Subclinical Antibody Mediated Rejection and Efficacy of Belatacept in the Context of de Novo Donor Specific Antibody After Kidney Transplantation (BELA-M-R)
A Phase 2/3 study testing Conversion to Belatacep in people with Kidney Transplant Rejection, run by University Hospital, Rouen at 1 site in France.
Trial summary
Antibody mediated rejection (ABMR) is a major cause of graft loss after kidney transplantation (KT) and is mainly associated with preformed anti-HLA donor specific antibodies (DSAs) (phenotype 1) or de novo DSAs (dnDSAs) (phenotype 2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Rejection
- What is being tested?
- Conversion to Belatacep
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 290 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jul 2026to 1 Aug 2032
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Screening inclusion criteria:
- Kidney transplant recipient
- Adult
- De novo DSA (MFI > 1000 using the Luminex single antigen beads assay or positive with the manufacturer criteria according to the Luminex assay) absent on the day of kidney transplantation and in the sera prior to kidney transplantation
- No clinical graft dysfunction at time of DSA detection (< 20 % variation of eGFR compared to last 3 months before detection and < 0,5 g/g proteinuria/creatinuria ratio)
- Affiliation with, or beneficiary of a Social security (national health insurance) category
Show all 12Show fewer
- Person having read and understood the information letter and signed the consent form
- Women of childbearing potential with effective contraception/very-effective contraception (Cf. CTFG) (oestro-progestatives or intra-uterine device or tubal ligation) and a negative blood pregnancy test.
- Women surgically sterile (absence of ovaries and/or uterus)
- Postmenopausal women: confirmation diagnostic (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit)
- Randomization inclusion criteria:
- Patients with active sABMR, according Banff 2019 classification, with very slight transplant glomerulogathy (cg = 0 or 1).
Who cannot join
- Screening exclusion criteria:
- Minor
- Specific treatment for DSA occurrence before kidney graft biopsy: IVIG or rituximab or plasmapheresis or immunoabsorption
- ABO incompatible kidney transplantation
- Combined transplantation
- Transplant recipients who are Epstein-Barr virus (EBV) seronegative or serostatus unknown.
Show all 17Show fewer
- Hypersensitivity to the active substance or to any of the excipients - Pregnant or parturient or breastfeeding woman or absence of contraception
- Person deprived of liberty by an administrative or judiciary decision or person placed under judicial protection, under guardianship or supervision
- Person consenting to the research participating to another trial
- Medical history or psychological or sensorial abnormality prone to inhibit the subject to understand the conditions required for his/her participation to the protocol or unable him/her to give an informed consent
- No signed ICF
- Randomization exclusion criteria:
- No sABMR or chronic active sABMR (cg > 1) on initial biopsy
- History of severe opportunistic infection before randomization
- Acute or chronic infection with HBV, HCV or HIV
- EBV negative serology
- History of post-transplant lymphoproliferative disorder.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
CHU de ROUEN
Rouen, 76031
Dominique Bertrand, Dr, 02 32 88 54 52, Dominique.Bertrand@chu-rouen.fr
Dominique Bertrand, Dr
About this study
Antibody mediated rejection (ABMR) is a major cause of graft loss after kidney transplantation (KT) and is mainly associated with preformed anti-HLA donor specific antibodies (DSAs) (phenotype 1) or de novo DSAs (dnDSAs) (phenotype 2). Preexisting DSA-associated ABMR have superior graft survival compared with dnDSA-associated ABMR, which could partly be explained by the fact that patients with de novo DSA-associated ABMR have biopsy later, when graft dysfunction and/or proteinuria are already present. ABMR is a progressive process with an early stage called subclinical ABMR (sABMR), in which histological lesions are present in the kidney graft without clinical graft dysfunction. These early lesions are now well recognized as risk factors for transplant glomerulopathy and poor graft survival in phenotype 1 ABMR (ref 5). The impact of sABMR associated with dnDSA at any time post-transplant has been less studied and reported. Recently, a retrospective multicenter study was published, within the Spiesser Group that included 123 patients without graft dysfunction who underwent graft biopsy because of the presence of dnDSA (One Lambda, MFI > 1000). Performing a kidney graft biopsy after dnDSA indentification without renal dysfunction leads to the diagnosis of active sABMR in 35 % of cases. Nevertheless, no effect of standard of care treatment in active sABMR was observed. Very recently, an expert consensus for the recommended treatment for ABMR after KT was published. It was conclude that the clear lack of evidence but a standard of care for ABMR was nevertheless defined. Therefore, the current proposal is to evaluate a new strategy for active sABMR, testing a conversion from calcineurin inhibitor (CNI) to belatacept associated with the recently recommended standard of care (SOC) compared to continuing CNI. Belatacept might help to manage nonadherence, decrease the toxicity of CNI on an endothelium already affected by microvascular inflammation, and reduce DSA titers.
The monitoring of dnDSA after KT and an indication graft biopsy in case of appearance, even in the absence of graft dysfunction, is not part of a routine clinical practice in all KT centers. This strategy could be a valuable option, in order to begin treatment of ABMR before graft dysfunction occurs, and therefore to improve prognosis associated with phenotype 2 ABMR. Parajuli et al.4 suggested that early diagnosis and treatment of sABMR with SOC, using DSA monitoring may improve outcomes after KT, but this is a retrospective and no-randomized study. This study will be the first prospective randomized study in the context of de novo DSA. The objective is to evaluate a new combination of treatment for ABMR in the context of dnDSA with subclinical lesions and in the same time may help to determine the real incidence of sABMR in KT recipients with subclinical dnDSA. The use of belatacept in the context of sABMR to improve the non-adherence and to decrease the endothelial toxicity had never been evaluated in a prospective way.
- Conditions
- Kidney Transplant Rejection
- Being tested
- Conversion to Belatacep, Standard of care treatment (SOC regimen) with Tacrolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conversion to BelatacepDrug
CNI will be tapered within 3 months: 75 % of initial dose on the first month, 50 % on the second month, 25 % on the third month, and stopped and a conversion to Belatacept will be performed. It will be administered (6mg/kg) every 2W for the first 2 months and then every month until kidney graft survival.
Standard of care treatment (SOC regimen) with TacrolimusDrug
Tacrolimus will be continued until kidney graft survival with objective of whole blood through levels between 6 and 8 ng/mL
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | - Experimental arm: conversion to Belatacept CNI will be tapered within 3 months: 75 % of initial dose on the first month, 50 % on the second month, 25 % on the third month, and stopped and a conversion to Belatacept will be performed. It will be administered (6mg/kg) every 2W for the first 2 months and then every month until kidney graft survival. Receives: Drug: Conversion to Belatacep |
| Control | Active comparator | - Control arm: Standard of care treatment (SOC regimen) with Tacrolimus Tacrolimus will be continued until kidney graft survival with objective of whole blood through levels between 6 and 8 ng/mL Receives: Drug: Standard of care treatment (SOC regimen) with Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The efficacy of belatacept combined with standard of care, compared to calcineurin inhibitors (CNI) combined with standard of care, among kidney transplant recipients with sABMR
Proportion in each arm, at 12 months post randomization, of patients with:
- decrease eGFR > 20% at 12 months post randomization, according to CKD-EPI formula
- or bad features on 12-month protocol biopsy: cg > 1
- or chronic active ABMR according Banff 2019 classification,
- or < 50 % MFI reduction of DSA,
- or proteinuria/creatinuria ratio > 0.5 g/g,
- or death,
- or graft loss.
Measured: over 12 months post-biopsy
Secondary outcomes (13)
Presence of chronic active ABMR
Presence of ABMR defined according to the Banff 2019 classification, assessed on the kidney graft biopsy
Measured: at 12 months post biopsy
Serum creatinine and calculation of eGFR
Assessment of renal function based on serum creatinine levels and estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI formula
Measured: 12 months and 36 months post biopsy
Proteinuria/creatininuria ratio
Evaluation of proteinuria using the proteinuria-to-creatininuria ratio measured on urine samples
Measured: 12 months and 36 months post biopsy
Significant Proteinuria
Proportion of patients presenting significant proteinuria, defined as a proteinuria-to-creatininuria ratio > 0.5
Measured: 12 months and 36 months post biopsy
Presence of Poor Prognostic Histological Features
Presence of unfavorable histological features, defined as transplant glomerulopathy with cg score > 1 according to Banff 2019 classification
Measured: 12 months post biopsy
Biopsy-Proven Acute T Cell-Mediated Rejection
Incidence of biopsy-proven acute T cell-mediated rejection, classified according to the Banff 2019 criteria
Measured: From biopsy to 36 months post biopsy
Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI)
Assessment of DSA MFI measured using a Luminex single antigen assay at 12 months post-V0 and collected from medical charts at 36 months post-randomization
Measured: 12 months post-biopsy and 36 months post-randomization
Insufficient Reduction in DSA MFI
Proportion of patients presenting a reduction in DSA MFI of less than 50% compared to baseline values.
Measured: 12 months post biopsy
Evaluation of Safety Outcomes (Adverse Events)
Collection and analysis of adverse events, including but not limited to viral reactivations (BK virus, CMV, EBV viremia), cardiovascular events, and other clinically significant adverse events.
Measured: Until the end of the study
Graft Loss and Death
Occurrence of graft loss and all-cause mortality, collected from medical charts.
Measured: 12 months and 36 months post biopsy
Renal Function and Proteinuria According to Initial Biopsy Groups
Comparison of serum creatinine, eGFR (CKD-EPI), and proteinuria-to-creatininuria ratio between patient groups defined according to the initial biopsy findings.
Measured: 12 months and 36 months post biopsy
Graft Loss and Death According to Initial Biopsy Groups
Comparison of graft loss and all-cause mortality between patient groups defined according to the initial biopsy findings.
Measured: 12 months and 36 months post biopsy
Incidence Rate of de novo Subclinical ABMR (sABMR)
Incidence rate of biopsy-proven subclinical ABMR (sABMR), defined according to Banff 2019 classification, in patients without sABMR at initial biopsy. The incidence will be expressed as the number of patients developing sABMR divided by the time elapsed between the initial biopsy and the first biopsy demonstrating sABMR.
Measured: From initial biopsy up to 12 months post biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2024
- Study start1 Jul 2026 (estimated)
- Primary completion1 Aug 2032 (estimated)
- Study completion1 Aug 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant RejectionStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06291103
- Sponsor's protocol ID
- 2022/0342/HP
- Acronym
- BELA-M-R
- Status last verified
- Jun 2026
- First submitted
- 26 Feb 2024
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Screening for Subclinical Antibody Mediated Rejection and Efficacy of Belatacept in the Context of de Novo Donor Specific Antibody After Kidney Transplantation (BELA-M-R)
- ClinicalTrials.gov ID
- NCT06291103
- Acronym / sponsor ID
- BELA-M-R / 2022/0342/HP
- Conditions
- Kidney Transplant Rejection
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 1 Aug 2032 (estimated)
- Study completion
- 1 Aug 2032 (estimated)
- First posted
- 4 Mar 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.
Antibody mediated rejection (ABMR) is a major cause of graft loss after kidney transplantation (KT) and is mainly associated with preformed anti-HLA donor specific antibodies (DSAs) (phenotype 1) or de novo DSAs (dnDSAs) (phenotype 2). Preexisting DSA-associated ABMR have superior graft survival compared with dnDSA-associated ABMR, which could partly be explained by the fact that patients with de novo DSA-associated ABMR have biopsy later, when graft dysfunction and/or proteinuria are already present. ABMR is a progressive process with an early stage called subclinical ABMR (sABMR), in which histological lesions are present in the kidney graft without clinical graft dysfunction. These early lesions are now well recognized as risk factors for transplant glomerulopathy and poor graft survival in phenotype 1 ABMR (ref 5). The impact of sABMR associated with dnDSA at any time post-transplant has been less studied and reported. Recently, a retrospective multicenter study was published, within the Spiesser Group that included 123 patients without graft dysfunction who underwent graft biopsy because of the presence of dnDSA (One Lambda, MFI > 1000). Performing a kidney graft biopsy after dnDSA indentification without renal dysfunction leads to the diagnosis of active sABMR in 35 % of cases. Nevertheless, no effect of standard of care treatment in active sABMR was observed. Very recently, an expert consensus for the recommended treatment for ABMR after KT was published. It was conclude that the clear lack of evidence but a standard of care for ABMR was nevertheless defined. Therefore, the current proposal is to evaluate a new strategy for active sABMR, testing a conversion from calcineurin inhibitor (CNI) to belatacept associated with the recently recommended standard of care (SOC) compared to continuing CNI. Belatacept might help to manage nonadherence, decrease the toxicity of CNI on an endothelium already affected by microvascular inflammation, and reduce DSA titers.
The monitoring of dnDSA after KT and an indication graft biopsy in case of appearance, even in the absence of graft dysfunction, is not part of a routine clinical practice in all KT centers. This strategy could be a valuable option, in order to begin treatment of ABMR before graft dysfunction occurs, and therefore to improve prognosis associated with phenotype 2 ABMR. Parajuli et al.4 suggested that early diagnosis and treatment of sABMR with SOC, using DSA monitoring may improve outcomes after KT, but this is a retrospective and no-randomized study. This study will be the first prospective randomized study in the context of de novo DSA. The objective is to evaluate a new combination of treatment for ABMR in the context of dnDSA with subclinical lesions and in the same time may help to determine the real incidence of sABMR in KT recipients with subclinical dnDSA. The use of belatacept in the context of sABMR to improve the non-adherence and to decrease the endothelial toxicity had never been evaluated in a prospective way.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Conversion to Belatacep- Experimental arm: conversion to Belatacept CNI will be tapered within 3 months: 75 % of initial dose on the first month, 50 % on the second month, 25 % on the third month, and stopped and a conversion to Belatacept will be performed. It will be administered (6mg/kg) every 2W for the first 2 months and then every month until kidney graft survival. |
| Control | Active comparator | Drug: Standard of care treatment (SOC regimen) with Tacrolimus- Control arm: Standard of care treatment (SOC regimen) with Tacrolimus Tacrolimus will be continued until kidney graft survival with objective of whole blood through levels between 6 and 8 ng/mL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Screening inclusion criteria:
- Randomization inclusion criteria:
Key exclusion criteria (17 listed)
- Screening exclusion criteria:
- Randomization exclusion criteria:
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 |
|---|---|---|
| Conversion to BelatacepCNI will be tapered within 3 months: 75 % of initial dose on the first month, 50 % on the second month, 25 % on the third month, and stopped and a conversion to Belatacept will be performed. It will be administered (6mg/kg) every 2W for the first 2 months and then every month until kidney graft survival. | Drug | Experimental |
| Standard of care treatment (SOC regimen) with TacrolimusTacrolimus will be continued until kidney graft survival with objective of whole blood through levels between 6 and 8 ng/mL | Drug | Control |
Primary outcome
The efficacy of belatacept combined with standard of care, compared to calcineurin inhibitors (CNI) combined with standard of care, among kidney transplant recipients with sABMR
Time frame: over 12 months post-biopsy
Proportion in each arm, at 12 months post randomization, of patients with: * decrease eGFR > 20% at 12 months post randomization, according to CKD-EPI formula * or bad features on 12-month protocol biopsy: cg > 1 * or chronic active ABMR according Banff 2019 classification, * or < 50 % MFI reduction of DSA, * or proteinuria/creatinuria ratio > 0.5 g/g, * or death, * or graft loss.
13 secondary outcomes
Presence of chronic active ABMR
Time frame: at 12 months post biopsy
Serum creatinine and calculation of eGFR
Time frame: 12 months and 36 months post biopsy
Proteinuria/creatininuria ratio
Time frame: 12 months and 36 months post biopsy
Significant Proteinuria
Time frame: 12 months and 36 months post biopsy
Presence of Poor Prognostic Histological Features
Time frame: 12 months post biopsy
Biopsy-Proven Acute T Cell-Mediated Rejection
Time frame: From biopsy to 36 months post biopsy
Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI)
Time frame: 12 months post-biopsy and 36 months post-randomization
Insufficient Reduction in DSA MFI
Time frame: 12 months post biopsy
Evaluation of Safety Outcomes (Adverse Events)
Time frame: Until the end of the study
Graft Loss and Death
Time frame: 12 months and 36 months post biopsy
Renal Function and Proteinuria According to Initial Biopsy Groups
Time frame: 12 months and 36 months post biopsy
Graft Loss and Death According to Initial Biopsy Groups
Time frame: 12 months and 36 months post biopsy
Incidence Rate of de novo Subclinical ABMR (sABMR)
Time frame: From initial biopsy up to 12 months post biopsy
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 9 Jun 2026.
Related trials for Kidney Transplant Rejection
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Not yet recruitingPhase 2
(TNX-1500) in Kidney Transplant Recipients
Kidney Transplant, Kidney Transplant Failure and Rejection
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
Not yet recruitingObservational study
Assessment of Perceived Stress in an Observational Study Evaluating a Biopsy-sparing Surveillance Strategy in Kidney Transplant Recipients With Blood and Urinary Biomarkers Predictive of the Absence of Rejection
Renal Transplantation; Complication, Renal Transplant
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Conversion to Belatacep in people with Kidney Transplant Rejection, run by University Hospital, Rouen at 1 site in France.
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 12 inclusion and 17 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: opening soon, as of the sponsor's last update on 9 Jun 2026. 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 France. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Dominique Bertrand, Dr (02 32 88 54 52, Dominique.Bertrand@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The efficacy of belatacept combined with standard of care, compared to calcineurin inhibitors (CNI) combined with standard of care, among kidney transplant recipients with sABMR (time frame: over 12 months post-biopsy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2026.