Clinical trial NCT01025193: Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant
Official title: One Year Exploratory Study to Evaluate the Efficacy and Safety of Belimumab for Normalization of Alloantibody Levels in Sensitized Patients Awaiting Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Desensitization
Keywords: belimumab
Benlysta
LymphoStat B
BLyS specific inhibitors
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Human Genome Sciences Inc.
First posted: 2009-12-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: There was only one group in this trial. All participants received belimumab.
Primary purpose: TREATMENT

Brief 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.

Detailed description: Approximately one third of patients awaiting kidney transplant at our transplant center have significant levels of antibodies in their blood leading to a longer wait time for a kidney transplant and death. Antibodies in the blood may be due to prior transplants, pregnancy, or blood transfusions. These antibodies sensitize a patient and make it more difficult for the patient to get a compatible kidney transplant. The measure of these antibodies is called panel reactive antibodies (PRA) and can range from 0-100%, with 100% being most sensitized. The waiting time for patients with a PRA in the range of 20%-79% is over 5 years as compared to patients with low PRA (0%-19%) which is 3-4 years. Patients with a PRA greater than 80% are likely to be granted extra points to increase the chances of transplantation. Antibodies in these patients may be due to prior transplants, pregnancy, or blood transfusions. To date, no trials with belimumab have been performed in patients with pre-existing antibodies awaiting kidney transplantation. This study is undertaken to assess the effectiveness and safety of using belimumab to normalize antibody levels in sensitized patients awaiting kidney transplantation. It is hoped that decreasing these antibodies will decrease the waiting time on the kidney transplant list, and allow the patient to become compatible with a donor kidney for transplant.

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.

Primary outcomes:
measure: Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.
timeFrame: up to one year pre-transplant
measure: Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
timeFrame: one year pre-transplant
Secondary outcomes:
measure: Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
timeFrame: Belimumab serum drug dilution factors were measured in patients at at timepoints 0 (first day of belimumab), day 14, day 56, day 168, 364, at any unscheduled visits, and at 8 weeks post completion of belimumab therapy.
measure: B and T Lymphocyte Subsets
timeFrame: 8 weeks after the last dose of belimumab
measure: BLyS Levels Before and After Treatment With Belimumab
timeFrame: up to 8 weeks after completion of therapy
measure: Hepatitis B Vaccine Antibody Titers
timeFrame: up to 12 months of treatment with belimumab
measure: Number of Participants With Treatment Related Serious Adverse Events
timeFrame: up to one year pre-transplant
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsyvlania Kidney Transplant Program
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Ali Naji, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References: