Immune Monitoring to Facilitate Belatacept Monotherapy

• 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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Rejection; Immunosuppression
• Intervention / Treatment: Diagnostic test: Allosure; Drug: Immunosuppression reduction; Diagnostic test: Trugraf

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Belatacept treated patients; Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone

Diagnostic test: Allosure; Monthly monitoring of dd-cfDNA levels in blood; Other Names: donor-derived cell-free DNA (dd-cfDNA); 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; Other Names: sirolimus; mycophenolate; prednisone; everolimus; Belatacept; Diagnostic test: Trugraf; Monthly monitoring of Trugraf result

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Rejection	Biopsy-proven according to Banff 2017 criteria	Enrollment through 12 months
Incidence of Acute Rejection	Biopsy-proven according to Banff 2017 criteria	Through study completion, 1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Transplant Genomics, Inc.; CareDx
• Investigators: Principal Investigator: Hannah Gilligan, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2020
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: November 22, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Immune Checkpoint Inhibitors; MTOR Inhibitors; Prednisone; Everolimus; Sirolimus; Abatacept
• Other Study ID Numbers: 2019P002608

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes