Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant

NCT01025193 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IND 106342
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Desensitization

Keywords

belimumab; Benlysta; LymphoStat B; BLyS specific inhibitors

Outcome Measures

Primary Outcomes (2)

• Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.

  Before transplant it is necessary to measure antibodies that the recipient might have and compare them to the living or decease donor's immune make-up. Recipients with many antibodies or a specific antibody in a high concentration may have a more difficult time finding a compatible donor, and being transplanted. These recipients are referred to as sensitized patients. It is important that the sensitized recipient and the donor be compatible to prevent rejection after transplant. We measured antibodies levels in sensitized patients waiting for kidney transplant, to see if belimumab would decrease these antibody levels.

  up to one year pre-transplant

• Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)

  In order for a sensitized recipient ( a recipient with antibodies) to be transplanted, the cross match with the donor has to be compatible. We wanted to study if belimumab reduced antibodies in sensitized patients and led those patients to subsequently become cross-match compatible with a donor and allow for successful transplant.

  one year pre-transplant

Secondary Outcomes (5)

• Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.

  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.

• B and T Lymphocyte Subsets

  8 weeks after the last dose of belimumab

• BLyS Levels Before and After Treatment With Belimumab

  up to 8 weeks after completion of therapy

• Hepatitis B Vaccine Antibody Titers

  up to 12 months of treatment with belimumab

• Number of Participants With Treatment Related Serious Adverse Events

  up to one year pre-transplant

Study Arms (1)

Belimumab

EXPERIMENTAL

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.

Drug: Belimumab

Interventions

Belimumab 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.

Also known as: registered name Benlysta, also previously known as LymphoStat-B

Belimumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Human Genome Sciences Inc.: collaborator

Study Sites (1)

University of Pennsyvlania Kidney Transplant Program

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

belimumab

Limitations and Caveats

Few patients enrolled, and limited follow-up due to trial being halted due to lack of efficacy after review by investigators and the data safety monitoring board. Only one patient was transplanted during the trial (unrelated to study treatment).

Results Point of Contact

• Title: Jennifer Trofe-Clark
• Organization: Hospital of the University of Pennsylvania

jennifer.trofe-clark@uphs.upenn.edu

215-614-4274

Study Officials

• Ali Naji, MD, Ph D

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: There was no masking in this single group trial. The patients, providers and investigators were all aware that the patient were on belimumab therapy.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There was only one group in this trial. All participants received belimumab.

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 3, 2009
• Study Start: February 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: November 1, 2011
• Last Updated: June 12, 2017
• Results First Posted: February 28, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)