Immune Monitoring to Facilitate Belatacept Monotherapy

Immunosuppression Clinical Trial

Official title:

Immune Monitoring to Facilitate Belatacept Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04177095
• Other study ID #: 2019P002608
• Status: Completed
• Phase: Phase 4
• Start date: February 11, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: December 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 1, 2023
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immunosuppression
• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Allosure
Monthly monitoring of dd-cfDNA levels in blood

Drug:
• Immunosuppression reduction
Stepwise reduction in the dose, and ultimate discontinuation of, all non-belatacept immunosuppression (mycophenolate, sirolimus, everolimus, prednisone) guided by monitoring of Allosure and Trugraf results

Diagnostic Test:
• Trugraf
Monthly monitoring of Trugraf result

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	CareDx, Transplant Genomics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Acute Rejection	Biopsy-proven according to Banff 2017 criteria	Enrollment through 12 months
Primary	Incidence of Acute Rejection	Biopsy-proven according to Banff 2017 criteria	Through study completion, 1 year
Secondary	Increase in eGFR	Calculated using CKD-EPI formula	From baseline to 12 months
Secondary	Rate of New-onset Proteinuria	Defined as g/g creatinine, measured on random urine sample	At 12 months
Secondary	Incidence of de Novo Donor Specific Antibodies	Screened for using Luminex platform	At 12 months
Secondary	Survival	Overall and death-censored graft survival	At 12 months