Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function

NCT ID: NCT01837043

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2017-06-30

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant.

Research Hypotheses:

Primary Hypotheses:

• Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity
• Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR.

Key Secondary Hypotheses:

• Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant
• Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.

Conditions

Delayed Graft Function; Kidney Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belatacept

Subjects will be converted from standard of care CNI therapy to Belatacept 10 mg/kg IV on post renal transplant Day 7 (+/- 3 days). As suggested in the package insert for de novo dosing, further dosing of belatacept will be given as 10 mg/kg IV at weeks 2, 4, 8 and 12 then 5 mg/kg at week 16 and then every 4 weeks (+/- 5 days) through week 52. CNI will be stopped during the first belatacept infusion.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Calcineurin Inhibitor

Patients randomized to this arm will remain on the current CNI as prescribed by post-transplant standard of care therapy.

Group Type: ACTIVE_COMPARATOR

Calcineurin Inhibitor

Intervention Type: DRUG

Interventions

Belatacept

Intervention Type: DRUG

Calcineurin Inhibitor

Intervention Type: DRUG

Other Intervention Names

Nulojix; Prograf, Tacrolimus, Cyclosporine

Eligibility Criteria

Inclusion Criteria

• Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
• All patients (> 18 years) who have received a deceased donor transplant and are at risk for SGF/DGF will be studied
• All gender and ethnicities will be considered in this study
• At risk for SGF/DGF is defined as:

• ECD (Extended Criteria Donor) donor kidney recipients
• ECD is defined as a donor over the age of 60 or age 50 to 60 with 2 of the following risk factors:
• Terminal creatinine > 1.5 mg/dL
• History of Hypertension
• Death due to cerebrovascular accident

• Donations after cardiac death (DCD) kidney recipients
• Donor organs with an actual cold ischemia time (CIT) > 19 hours
• Recipients of donor organs with a terminal creatinine > 1.5 mg/dL
• Only patients who receive Thymoglobulin induction and CNI maintenance at time of randomization will be considered for the study
• Men and women, 18 to 70 years of age
• Reproductive status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal.

Post-menopause is defined as:

• Women who have had amenorrhea for >= 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH)level > 35 mIU/mL
• Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL
• Women who are taking hormone replacement therapy

The following are WOCBP:

• Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
• Women who are practicing abstinence
• Women who have a partner who is sterile (due to vasectomy)
• WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized
• WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug.
• Women must not be breast-feeding
• Sexually active fertile men must use effective birth control if their partners are WOCBP

Exclusion Criteria

• Seronegative or unknown EBV (Epstein Barr Virus) serostatus (due to the risk of posttransplant lymphoproliferative disorder, PTLD) predominantly involving the central nervous system
• Patients with tuberculosis who have not been treated for latent infection
• Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
• Rejection episode before randomization
• Anatomic cause of SGF/DGF such as urinary leak, obstruction or thrombosis
• Patients with a prior or concurrent non-renal solid organ transplant
• Patients with living donor kidneys
• Patients with pediatric kidneys (age of less than 5 years)
• Dual kidney transplants (from the same donor)
• Immunologically high risk patients with a positive crossmatch pre- transplantation or donor specific antibody (DSA) > 5000 MFI
• ABO Incompatible transplantation
• Patients with HIV
• Subjects with any active infection or other contraindication that would normally exclude transplantation
• Patients with a history of malignancy in the last 5 years except non- melanoma skin cancer
• Baseline white blood cell count less than 2,000
• Baseline hemoglobin less than 8 g/dL
• Patients with prior allergic reactions to belatacept
• Patients with prior allergic reactions to thymoglobulin
• Sex and Reproductive status - see WOCBP information in inclusion above
• Subjects currently receiving immunosuppressive agent(s) for other indications such as an autoimmune disease or subjects with comorbidities that treatment with such agents are likely during the trial.
• Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
• Subjects previously treated with belatacept
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Nair, Vinay, D.O.

INDIV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vinay Nair, D.O.

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai School of Medicine Recanati/Miller Transplantation Institute

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Vinay Nair, D.O.

Role: CONTACT

Vinay.Nair@mountsinai.org

212-659-8086

Brandy M Haydel, CCRC

Role: CONTACT

Brandy.Haydel@mountsinai.org

212-241-0255

Facility Contacts

Vinay Nair, D.O.

Role: primary

Vinay.Nair@mountsinai.org

212-659-8086

Brandy Haydel, CCRC

Role: backup

Brandy.Haydel@mountsinai.org

212-241-0255

Other Identifiers

13-00174

Identifier Type: OTHER

Identifier Source: secondary_id

IM103-057

Identifier Type: -

Identifier Source: org_study_id