Belatacept (Nulojix) in Renal Transplant Recipient With Mild Immunologic Risk Factor: a Pilot Prospective Study. (BELACOR)

July 1, 2019 updated by: Assistance Publique - Hôpitaux de Paris

Belatacept (Nulojix) in Renal Transplant Recipient With Mild Immunologic Risk Factor: a Pilot Prospective Study

BACKGROUND: Antibody-mediated humoral rejection is currently a critical question in renal transplant recipient with immunological risk factors such as pre transplant donor-specific anti HLA antibodies (DSA). The immunosuppressive management of the patients is still not well defined and improving both short and long-term graft outcome remains a challenging question. Recent experimental data suggest that Belatacept could induce B cell anergy , induce regulatory B cell and decrease Ig production. These findings are strengthened by the results of both phase II and III clinical studies, showing a significant lower incidence of DSA in patients treated with Belatacept compared to recipients receiving a conventional immunosuppressive regimen with calcineurin inhibitors (CNI).

Primary objective will be the incidence of clinical and subclinical humoral rejection (According to BANFF 2011 Criteria). Secondary objectives will include one-year graft and patient survival, renal function at M12 (MDRD), incidence of cellular rejection (M 12), level of proteinuria (M3 and M12) and DSA outcome (outcome of DSA MFI at JO, M3 and M12). Inclusion period will be of two years. DSA identification and quantitative analysis before and after transplantation will be centralized in only one HLA laboratory Unit (Hospital Saint Louis) for providing results homogeneity.

According to previous clinical studies, the incidence of Acute Antibody Mediated Humoral Rejection is close to 20% in patients with mild immunological risk defined by the presence of DSA at the time of transplant with mean fluorescence intensity (MFI) between 1000 and 3000 (Luminex). In order to demonstrate a significant reduction (40%) of AAMR and sAAMR incidence, 91 patients will be included in this study. Results will be compared to a cohort matched for age, sex, immunological risk factor (DSA), time of transplant, transplant center and grafted with a similar immunosuppressive regimen including CNI instead of Belatacept

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Creteil, France, 94010
        • Henri Mondor Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed Written Informed Consent

    a) 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.

  2. Target Population

    a) Renal transplant recipients aged over 18 with DSA at the time of transplant and or on historic serum with mean fluorescence intensity (MFI) between 500 and 3000 (Luminex), available at the time of the transplant.

  3. Age and Sex

    1. Men and women, ages >18
    2. Women of childbearing potential (WOCBP) must be using two adequate methods of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug to minimize the risk of pregnancy.

    WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:

    • Amenorrhea that has lasted for 12 consecutive months or more without another cause, or
    • For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.

    Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.

    WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product.

    A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 8 weeks after the last dose of study drug to minimize the risk of pregnancy.

    Exclusion Criteria:

  4. Sex and Reproductive Status

    1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug.
    2. Women who are pregnant or breastfeeding.
    3. Women with a positive pregnancy test.
    4. Sexually active fertile men not using effective birth control if their partners are WOCBP.

  5. Target Disease Exceptions

    1. Subjects who are EBV-negative or whose EBV status is unknown..
    2. Renal Transplantation of Focal and Segmental Glomerulosclerosis
  6. Medical history and concomitant diseases
  7. Patient with past history of malignancy
  8. Physical and Laboratory Test Findings: DSA <500 or>3000
  9. Allergies and Adverse Drug Reactions to Nulojix

  10. Other Exclusion Criteria

    1. Prisoners, or subjects who are involuntarily incarcerated.
    2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nulojix
Drug: Nulojix (Belatacept)
Nulojix Administration will start the day of transplantation (day 1 and first dosing day);10 mg/kg : (day1, 5,14,28 ), Week 8 and 12 and then 5 mg/kg every 4 weeks until Month 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Acute Antibody Mediated Rejection (AAMR) (According to BANFF 2011 Criteria)
Time Frame: 12 months (+/- 3 months)
12 months (+/- 3 months)

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of subclinical AAMR diagnosed on protocol biopsy
Time Frame: 3 months (+/- 1 month), 12 months (+/- 3 month)
3 months (+/- 1 month), 12 months (+/- 3 month)
Number of patient survival
Time Frame: 12 months (+/- 3 months)
12 months (+/- 3 months)
Number of graft survival
Time Frame: 12 months (+/- 3 months)
12 months (+/- 3 months)
Renal function measure by creatinine clearance (ml/min) (MDRD formula)
Time Frame: 3 months (+/- 1 month), 12 months (+/- 3 months)
3 months (+/- 1 month), 12 months (+/- 3 months)
Incidence of clinical and subclinical cellular rejection
Time Frame: 12 months (+/- 3 months)
12 months (+/- 3 months)
Renal function by level of proteinuria (in g/l)
Time Frame: 3 months (+/- 1 month), 12 months (+/- 3 months)
3 months (+/- 1 month), 12 months (+/- 3 months)
Donor Specific Antibody (DSA) level, evaluate by the measure of maximal Mean Fluorescence Intensity (MFI)by Luminex Single Antigen
Time Frame: 3 months (+/- 1 month), 12 months (+/- 3 months)
3 months (+/- 1 month), 12 months (+/- 3 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Philippe GRIMBERT, PU-PH, Assistance Publique - Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2014

Primary Completion (Actual)

September 18, 2017

Study Completion (Actual)

September 18, 2017

Study Registration Dates

First Submitted

January 5, 2016

First Submitted That Met QC Criteria

April 11, 2016

First Posted (Estimate)

April 14, 2016

Study Record Updates

Last Update Posted (Actual)

July 5, 2019

Last Update Submitted That Met QC Criteria

July 1, 2019

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P121203

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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