Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant

NCT ID: NCT01025193

Last Updated: 2017-06-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2011-11-30

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.

Conditions

Desensitization

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belimumab

Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.

Group Type: EXPERIMENTAL

Belimumab

Intervention Type: DRUG

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.

Interventions

Belimumab

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 Type: DRUG

Other Intervention Names

registered name Benlysta; also previously known as LymphoStat-B

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Human Genome Sciences Inc.

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ali Naji, MD, Ph D

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsyvlania Kidney Transplant Program

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

IND 106342

Identifier Type: -

Identifier Source: org_study_id