Precision Medicine Offers Belatacept Monotherapy

NCT ID: NCT02939365

Last Updated: 2022-12-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-28
• Study Completion Date: 2022-12-31

Brief Summary

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.

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.

Conditions

Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Nulojix®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Flavio Vincenti

Professor of Clinical Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Flavio Vincenti, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Other Identifiers

IM103-382

Identifier Type: -

Identifier Source: org_study_id