Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores

End-Stage Renal Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01496417
• Other study ID #: HP00048573
• Status: Completed
• Phase: N/A
• Start date: March 2012
• Est. completion date: March 1, 2018

Study information

• Verified date: June 2018
• Source: University of Maryland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 1, 2018
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Failure, Chronic

Intervention

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.

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. doi: 10.1097/TP.0b013e3181ff87cd. — View Citation

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. doi: 10.1681/ASN.2009111109. Epub 2010 Jul 15. — View Citation

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. doi: 10.1111/j.1600-6143.2009.03005.x. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Function	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.	12 months
Secondary	Rejection rate	Secondary objectives include the biopsy proven rejection rates at 12 months and comparison to existing cohorts of calcineurin inhibitor treated patients.	12 months
Secondary	Graft survival	Secondary objectives include renal allograft survival at 12 months.	12 months
Secondary	MAPI biopsy score	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.	12 months
Secondary	Patient survival	Secondary objectives include patient survival at 12 months.	12 months

External Links

•   University of Maryland Division of Transplantation