Desensitization With Belimumab in Sensitized Patients Awa... | NCT01025193

NCT01025193

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Human Genome Sciences Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.	We wanted to look at belimumab pharmacokinetics in sensitized patients awaiting kidney transplant. These are reported as number of participants with specific dilution factors at each studied time-point. Blood for these tests could be drawn pre dose as well as 0-4 hours after the dose was given. Belimumab dilutions factors were measured pre dose at timepoints 0 (first day of belimumab), days 56 and 364. Belimumab dilution factors were measured after the dose on days 14, and 168. Belimumab dilution factors were also measured at 8 weeks after completion of belimumab therapy and pre dose at any unscheduled visits if needed.

Eligibility Module

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.

Name	Affiliation	Role
Ali Naji, MD, Ph D	University of Pennsylvania	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Pennsyvlania Kidney Transplant Program		Philadelphia	Pennsylvania	19104	United States

Arm/Group Information

ID	Title	Description
FG000	Belimumab	Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was being used to try to decrease the amount of antibodies in the subject's blood pre-kidney transplant. This use was considered investigational (not approved by the Food and Drug Administration). Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Belimumab	Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was used in to try to decrease the amount of antibodies in the pre-kidney transplant patient's blood. This use was considered investigational (not approved by the Food and Drug Administration). Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

any patient who received at least one dose of belimumab was included in analysis population

Posted

Count of Participants

Participants

up to one year pre-transplant

ID	Title	Description
OG000	Belimumab

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Belimumab	Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was used to try to decrease the amount of antibodies in the patient waiting for kidney transplant's blood. This use was considered investigational (not approved by the Food and Drug Administration). Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial Fibrillation	Cardiac disorders		Systematic Assessment	unrelated to study drug

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Rash left antecubitus from adhesive tape	Skin and subcutaneous tissue disorders		Systematic Assessment	unrelated to study drug

Title	Organization	Phone	Extension	Email
Jennifer Trofe-Clark	Hospital of the University of Pennsylvania	215-614-4274		jennifer.trofe-clark@uphs.upenn.edu

ID	Term
C511911	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.

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.