Immune Monitoring to Facilitate Belatacept Monotherapy

Phase 4

Completed

• Conditions: Kidney Transplant Rejection; Immunosuppression
• Interventions: Diagnostic Test: Allosure; Drug: Immunosuppression reduction; Diagnostic Test: Trugraf

• Registration Number: NCT04177095
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

* To determine the utility of novel blood-based immune monitoring tools (Allosure and Trugraf) to facilitate belatacept monotherapy.

* To determine the percent of belatacept-treated renal transplant patients that can be safely converted to belatacept monotherapy.

Detailed Description

This study will examine whether renal transplant recipients treated with a belatacept-based immunosuppressive regimen can safely be weaned off all non-belatacept immunosuppression (mycophenolate, mTORi, prednisone) in a stepwise fashion. To this end, participants will undergo monthly "immune monitoring" using the Allosure (dd-cfDNA) and Trugraf (RNA profiling) blood tests to determine if they are in a state of immune quiescence. Only patients who are deemed to be immune quiescent, will continue to be weaned of non-belatacept immunosuppression.

Study Timeline

• Study First Submitted: 2019-11-22
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-26
• Study Start: 2020-02-11
• Primary Completion: 2021-09-30
• Study Completion: 2023-06-01
• Results First Submitted: 2023-10-06
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-01
• Last Update Submitted: 2023-12-01
• Results First Posted: 2023-12-04
• Last Update Posted: 2023-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Age minimum 18 years
• Written informed consent
• Single kidney transplant recipient (i.e. no combined organ transplants)
• Treated with de novo belatacept since transplantation (i.e. no previous use of calcineurin inhibitor or mTOR inhibitor for the current transplant)
• At least 1 year after transplantation or after initiation of belatacept
• Stable renal function (eGFR > 40 ml/min continuously during previous 6 months)
• Blood biomarkers indicate immune quiescence (for Allosure this corresponds to dd-cfDNA < 1%; for Trugraf this corresponds to "TX" signature)
• No history of BK viremia in current allograft

Exclusion Criteria

• History of biopsy-proven acute rejection
• Presence of donor-specific antibodies (at any MFI)
• Spot urine protein/creatinine ratio > 0.5 g/g

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Belatacept treated patients	Allosure	Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone
Belatacept treated patients	Immunosuppression reduction	Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone
Belatacept treated patients	Trugraf	Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone

Primary Outcome Measures

Name	Time	Method
Incidence of Acute Rejection	Through study completion, 1 year	Biopsy-proven according to Banff 2017 criteria

Secondary Outcome Measures

Name	Time	Method
Increase in eGFR	From baseline to 12 months	Calculated using CKD-EPI formula
Survival	At 12 months	Overall and death-censored graft survival
Rate of New-onset Proteinuria	At 12 months	Defined as g/g creatinine, measured on random urine sample
Incidence of de Novo Donor Specific Antibodies	At 12 months	Screened for using Luminex platform

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States