Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant
Condition: Desensitization
Intervention: Belimumab
Intervention description: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
Intervention MeSH terms: Belimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: There was only one group in this trial. All participants received belimumab.
Masking: None (Open Label)
Masking description: There was no masking in this single group trial. The patients, providers and investigators were all aware that the patient were on belimumab therapy.
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: belimumab; Benlysta; LymphoStat B; BLyS specific inhibitors

Summary:

      If subjects are listed for kidney transplant and are considered sensitized, this means they
      have a high amount of antibodies in their blood that could react to a kidney transplant
      offered for them. Antibodies are protein substances made by the body that fight anything that
      the body considers as a threat to it, such as infection or a kidney transplant. Sensitization
      may be due to prior transplants, pregnancy, or blood transfusions. Being sensitized can
      increase the subject's kidney transplant waiting time as it is more difficult to find a
      suitable kidney transplant for them that their antibodies will not react to. The purpose of
      this research study is to see if giving the investigational drug belimumab up to one year
      pre-transplant can de-sensitize the subjects, or decrease the amount of antibodies in their
      blood. This may help make the subjects eligible to receive a kidney transplant more quickly.
      If after receiving belimumab, the subjects are compatible with a donor kidney offered and are
      medically suitable for transplant at that time, a kidney transplant will be performed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients aged 18 -75 years.

          -  Patients denied a kidney transplant because of a prior positive crossmatch

          -  Patients awaiting a first or second kidney transplant from a living or deceased donor

          -  Patients who have given written informed consent to participate in all aspects of the
             study.

          -  Patients with no potential living donors should have accumulated at least 12 months
             waiting time in our organ procurement organization

          -  And one of the following criteria:

          -  Pre-sensitized patients defined by Luminex antibody assays and whose panel reactive
             antibody (PRA) is 20% or greater

          -  Patients with a PRA of less than 20% but who have HLA antibody specificities to
             HLA-Cw, DP or allele-specific antigens

        Exclusion Criteria:

          -  Patients with known hypersensitivity to belimumab or who have received biologics,
             within the last 90 days

          -  Patients receiving corticosteroids, intravenous immunoglobulin, cyclophosphamide,
             mycophenolate mofetil, or azathioprine from 90 days prior to study entry until day of
             transplant.

          -  Patients with a history of anaphylaxis to parenteral administration of contrast
             agents, foreign proteins, or monoclonal antibodies.

          -  Patients with multi-organ transplant

          -  Patients who have received any investigational immunosuppressive drug within 1 month
             of inclusion into this study or if use of such a product is anticipated.

          -  Patients who have received any live vaccine within 30 days of study entry.

          -  Female patients who are pregnant, lactating.

          -  Female patients of child bearing potential and not willing to practice an approved
             method of birth control for 1 month prior to the start of the study agent and 8 weeks
             after the last dose of study agent.

          -  Male patients who are not agreeable to using effective contraception throughout the
             study and for 3 months after the last dose of study agent.

          -  Patients with a known malignancy or history of malignancy other than excised basal or
             squamous cell carcinoma of the skin.

          -  Patients who are positive for Hepatitis B infection, Hepatitis C infection or Human
             Immunodeficiency Virus (HIV)-positive patients.

          -  Patients with evidence of severe liver disease, including abnormal liver profile tests
             > 3 times upper limit of normal at screening.

          -  Patients with current severe infection.

          -  Patients with any surgical or medical condition, which in the opinion of the
             investigator precludes enrollment in this trial

          -  Patients who live far from the transplant center and are unable to comply with all
             study visits.