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

NCT01496417 | Completed DMC

• 1 other identifier: HP00048573
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

End-Stage Renal Disease

Keywords

Kidney Transplantation; Biopsy; Belatacept

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Rejection rate

  12 months

• Graft survival

  12 months

• MAPI biopsy score

  12 months

• Patient survival

  12 months

Study Arms (1)

Belatacept therapy

EXPERIMENTAL

20 Patients receiving belatacept based immunosuppressive protocol for 12 months post-transplantation.

Drug: Belatacept

Interventions

Belatacept DRUG

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.

Also known as: Nulojix

Belatacept therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Related Publications (5)

• Vincenti F, Blancho G, Durrbach A, Friend P, Grinyo J, Halloran PF, Klempnauer J, Lang P, Larsen CP, Muhlbacher 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.

  PMID: 20634298 BACKGROUND

• 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. doi: 10.1056/NEJMoa050085.

  PMID: 16120857 BACKGROUND

• 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.

  PMID: 20415897 BACKGROUND

• Larsen CP, Grinyo 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.

  PMID: 21076381 BACKGROUND

• Sparkes T, Ravichandran B, Opara O, Ugarte R, Drachenberg CB, Philosophe B, Bromberg JS, Barth RN. Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts. Clin Transplant. 2019 Jun;33(6):e13531. doi: 10.1111/ctr.13531. Epub 2019 Apr 11.

  PMID: 30866104 DERIVED

Related Links

• University of Maryland Division of Transplantation

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Rolf N Barth, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: December 21, 2011
• Study Start: March 1, 2012
• Primary Completion: February 28, 2017
• Study Completion: March 1, 2018
• Last Updated: June 14, 2018

Record last verified: 2018-06

Locations

US (1)