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

NCT01837043 | Unknown Phase 2 DMC

• 2 other identifiers: IM103-05713-00174
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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

Keywords

Delayed Graft Function; Renal Transplantation; Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• cGFR

  Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.

  12 months

Secondary Outcomes (9)

• Renal Histology

  12 months

• Biomarker profile

  12 months

• Duration of Delayed (or slow) Graft Function

  12 months

• Incidence of Acute Rejection

  12 months

• New Onset Diabetes

  12 months

Study Arms (2)

Belatacept

EXPERIMENTAL

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.

Drug: Belatacept

Calcineurin Inhibitor

ACTIVE COMPARATOR

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

Drug: Calcineurin Inhibitor

Interventions

Belatacept DRUG

Also known as: Nulojix

Belatacept

Calcineurin Inhibitor DRUG

Also known as: Prograf, Tacrolimus, Cyclosporine

Calcineurin Inhibitor

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nair, Vinay, D.O.: lead
• Icahn School of Medicine at Mount Sinai: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Mount Sinai School of Medicine Recanati/Miller Transplantation Institute

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Delayed Graft Function

Interventions

Abatacept; Calcineurin Inhibitors; Tacrolimus; Cyclosporine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Study Officials

• Vinay Nair, D.O.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vinay Nair, D.O.

CONTACT

212-659-8086; Vinay.Nair@mountsinai.org

Brandy M Haydel, CCRC

CONTACT

212-241-0255; Brandy.Haydel@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2013
• First Posted: April 22, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: January 30, 2017

Record last verified: 2017-01

Locations

US (1)