Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores - Full Text View

Purpose

This will be a pilot study to investigate the use of belatacept (BMS) therapy in kidney transplant patients who have a MAPI score of greater than or equal to 8. The MAPI (Maryland Aggregate Pathology Index) score is a preimplantation donor scoring system which has five histopathological parameters that impact long-term kidney outcomes. Many kidney transplant recipients use calcineurin inhibitors (CNIs) as one of their anti-rejection medi cations. Kidney function may be affected by anti-rejection medications known as calcineurin inhibitors (CNIs). Sometimes CNIs can lead to toxicities and eventually loss of the kidney or episodes of chronic allograft nephropathy (CAN). Avoiding CNI immunosuppression and using belatacept therapy (BMS) instead, may be associated with improved kidney transplant outcomes.

Condition	Intervention
End-Stage Renal Disease	Drug: Belatacept

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 12 Month, Single-center, Non-randomized, Open-label Study of Outcomes of Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores in de Novo Renal Transplant Recipients

Resource links provided by NLM:

MedlinePlus related topics: Kidney Failure Kidney Transplantation

Drug Information available for: Belatacept

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Renal Function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
To evaluate renal function in Belatacept treated recipients of intermediate risk MAPI score allografts in terms of estimated glomerular filtration rate (eGFR, calculated using the MDRD formula) assessed at 12 months. The 12 month eGFR will be compared to existing cohorts of calcineurin inhibitor treated patients with MAPI scores above 8.

Secondary Outcome Measures:

Rejection rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Secondary objectives include the biopsy proven rejection rates at 12 months and comparison to existing cohorts of calcineurin inhibitor treated patients.
Graft survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Secondary objectives include renal allograft survival at 12 months.
MAPI biopsy score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Secondary objectives include the MAPI score at 3 and 12 months. The MAPI score change compared to baseline in the study group will be important in comparison to existing cohorts of calcineurin inhibitor treated patients, to determine whether calcineurin free-regimens are associated with both functional and histologic differences as compared to calcineurin based therapies.
Patient survival [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Secondary objectives include patient survival at 12 months.

Estimated Enrollment:	20
Study Start Date:	March 2012
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Belatacept therapy 20 Patients receiving belatacept based immunosuppressive protocol for 12 months post-transplantation.	Drug: Belatacept Belatacept infusion intravenous at 10 mg/kg on post-operative days 1, 5, and weeks 2, 4, 8, 12; 5mg/kg intravenous dose at weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48. Other Name: Nulojix

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female renal recipients 18-70 years of age undergoing primary kidney transplantation.
Recipients of deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death) with MAPI score ≥ 8.
Cold ischemic time less than 40 hours at time of reperfusion.
Negative serum pregnancy test for female patients.
Patients who can understand the purposes and risks of the study, provide informed consent, and can comply with the treatment and follow-up requirements.

Exclusion Criteria:

Cold ischemic time (CIT) > 40 hours
Patients who are sensitized with current PRA>40%, ABO incompatible transplants, or T, or B cell crossmatch positive transplant.
Patients without antibody to EBV
Patients receiving multiple organ transplants.
Patients unable to take oral medication at time of randomization
Patient with a history of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of carcinoma in situ
Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen.
Recipients of organs from donors who test positive for HIV, Hepatitis C or Hepatitis B surface antigen
Patients with a clinically significant systemic infection within 30 days prior to transplant
Patients who have cardiac failure at time of screening or any other severe cardiac disease as determined by the investigator
Patients with abnormal laboratory findings of clinical significance within 2 weeks of randomization which would interfere with the objectives of the study.
Females, pregnant or lactating, or are of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant.
Patient with active tuberculosis infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496417

Contacts

Contact: Rolf N Barth, MD	4438412222	rbarth@smail.umaryland.edu
Contact: Ilze Sikorski, RN	4103280303	isikorski@smail.umaryland.edu

Locations

United States, Maryland
University of Maryland Medical Center	Not yet recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Rolf N Barth, MD
Sub-Investigator: Benjamin Philosophe, MD, PhD

Sponsors and Collaborators

University of Maryland

Bristol-Myers Squibb

Investigators

Principal Investigator:

Rolf N Barth, MD

University of Maryland

More Information

Additional Information:

University of Maryland Division of Transplantation This link exits the ClinicalTrials.gov site

Publications:

Vincenti F, Blancho G, Durrbach A, Friend P, Grinyo J, Halloran PF, Klempnauer J, Lang P, Larsen CP, Mühlbacher F, Nashan B, Soulillou JP, Vanrenterghem Y, Wekerle T, Agarwal M, Gujrathi S, Shen J, Shi R, Townsend R, Charpentier B. Five-year safety and efficacy of belatacept in renal transplantation. J Am Soc Nephrol. 2010 Sep;21(9):1587-96. Epub 2010 Jul 15.

Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B; Belatacept Study Group. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Aug 25;353(8):770-81.

Vincenti F, Charpentier B, Vanrenterghem Y, Rostaing L, Bresnahan B, Darji P, Massari P, Mondragon-Ramirez GA, Agarwal M, Di Russo G, Lin CS, Garg P, Larsen CP. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010 Mar;10(3):535-46.

Larsen CP, Grinyó J, Medina-Pestana J, Vanrenterghem Y, Vincenti F, Breshahan B, Campistol JM, Florman S, Rial Mdel C, Kamar N, Block A, Di Russo G, Lin CS, Garg P, Charpentier B. Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies. Transplantation. 2010 Dec 27;90(12):1528-35.

Responsible Party:	Rolf Barth, MD, Principal Investigator, University of Maryland
ClinicalTrials.gov Identifier:	NCT01496417 History of Changes
Other Study ID Numbers:	HP00048573
Study First Received:	December 14, 2011
Last Updated:	December 20, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Maryland:

Kidney Transplantation
Biopsy
Belatacept

Additional relevant MeSH terms:

Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Abatacept

Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013