Precision Medicine Offers Belatacept Monotherapy (PROBE)

Precision Medicine Offers Belatacept Monotherapy (PROBE)

The purpose of this study is to determine the safety and feasibility of converting patients to Belatacept monotherapy (receiving just one immunosuppression drug), and to see what percentage of those patients can be safely converted to once every 8 week administration of Belatacept. Belatacept has been approved by the Food and Drug Administration (FDA) for kidney transplant recipients.

Study Overview

• Status: Withdrawn
• Conditions: Transplantation
• Intervention / Treatment: Drug: Belatacept

Detailed Description

Patients on belatacept who fulfill the entry criteria will be screened to determine if they have a quiescent molecular immunologic profile with kSORT and uCRM. Patients who screen negative on all 2 tests will undergo stepwise withdrawal first of steroids then of MMF or mTor inhibitors. Prior to each withdrawal the 2 screening molecular tests will be performed and advancement to the next withdrawal phase will be performed if both are negative. Patients who are maintained on belatacept monotherapy with quiescent kSORT and uCRM and elevated kSPOT will be transitioned to q 8 weeks belatacept administration.

Forty patients who are previously enrolled in belatacept based regimens with a minimum of 7 years of follow up at 4 transplant centers and who are maintained on belatacept, an antiproliferative ± steroids will be approached for enrollment.

Drug withdrawal of steroids (in patients on steroids) and of antiproliferatives (MPAs or mTor inhibitors) will follow the design shown in the Study Schema. Patients who continue to be stable for 3 months on belatacept monotherapy will be converted from q 4 weeks to q 8 weeks belatacept administrations.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stable renal function with a GFR ≥ 35 ml/min
• No history of acute rejection
• A spot urine protein creatinine ratio of 0.5 or less
• No DSA

Entry: Biomarker criteria

• Blood kSORT and urine CRM tests that are quiescent at entry and following each drug withdrawal.
• A third biomarker KSPOT will be used to assess if any patients has achieved tolerance.

Eligibility for 8 week Belatacept Administration

• Trough levels of belatacept at 4 weeks of greater than 2 µg/ml
• Trough levels of belatacept at 8 weeks of equal or greater than 1 µg/ml

Exclusion Criteria:

• Patients with < eGFR (35 ml/min)
• History of rejection
• Protein/creatinine rate >0.5
• Presence of DSA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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 patients; Forty patients who are previously enrolled in belatacept based regimens with a minimum of 7 years of follow up at 4 transplant centers and who are maintained on belatacept, an antiproliferative ± steroids will be approached for enrollment. Drug withdrawal of steroids (in patients on steroids) and of antiproliferatives (MPAs or mTor inhibitors). Patients who continue to be stable for 3 months on belatacept monotherapy will be converted from q 4 weeks to q 8 weeks belatacept administrations.

Drug: Belatacept; The transition to belatacept monotherapy and possibly to q 8 weeks administration can be safely done by applying personalized (i.e. precision) medicine. This includes phenotypic analysis of lymphocyte subsets, a quiescent molecular profiling of blood and urine prior to drug withdrawal and immune monitoring with KSORT after stepwise withdrawal of steroids and antiproliferatives. Furthermore, trough PK of belatacept will be measured for conversion to q 8 week therapy for discovering research purposes.; Other Names: Nulojix®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent patients converted to belatacept	To determine the percent of patients that can be safely converted to belatacept monotherapy	12 months
Percent patients safely converted to q8 week administration	2. To determine the percent of patients on belatacept monotherapy that can be safely converted to 8 week administration of belatacept	12 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Flavio Vincenti, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: October 18, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (Estimate): October 20, 2016

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM103-382

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No