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A Study of Belimumab to Help Identify Safe Kidney Transplant Matches in Patients with High Antibody Levels Against Donor Tissue Types

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is studying people who are waiting for a kidney transplant and have a condition called high HLA-immunization in transplant candidates. These are patients whose immune system has developed many antibodies against different tissue types, making it very difficult to find a matching kidney donor. The study will also include people who have experienced antibody-mediated rejection of renal grafts, which means their immune system has attacked a transplanted kidney in the past. The treatment being tested is Benlysta, which contains the active substance belimumab. This medication is given as an injection under the skin using a pre-filled syringe. The purpose of the study is to see if belimumab can help identify which specific tissue types a patient's immune system is truly reacting against, which could help doctors remove some antibodies from the unacceptable list and make it easier for these patients to receive a kidney transplant.

During the study, patients will receive belimumab injections for four weeks. The medication works by affecting certain immune cells called memory B-cells, which are responsible for producing antibodies. By influencing these cells, the medication may help them move from areas like lymph nodes into the bloodstream, where they can be tested more accurately. Doctors will take blood samples before treatment starts, during the four weeks of treatment, and at several time points afterward up to 36 weeks. These blood samples will be analyzed to see which specific tissue types the patient's immune system is reacting against and whether the pattern of antibodies changes over time.

The study will measure several things, including how many specific tissue type antibodies are found in the blood before and after treatment, whether the list of unacceptable tissue types for transplant can be reduced, and whether this improves the chances of finding a matching donor. For patients who receive a transplant after participating in the study, doctors will track whether the transplanted kidney is rejected, whether new antibodies develop, and whether the kidney continues to work properly. The study will also monitor the safety of the treatment by recording any side effects that occur during and after the four weeks of belimumab treatment.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial screening and confirmation of eligibility
Your eligibility for the study will be confirmed. This includes verification that you are between 18 and 75 years of age, that you are a candidate for a kidney transplant, and that you are highly-sensitized, meaning you have a very low probability of being matched with a donor organ.
If you are female, a pregnancy test will be performed to confirm you are not pregnant. You must agree to use proper contraception during the study if you are of child-bearing potential.
Step 2
Baseline assessments before treatment begins
Blood samples will be collected to analyze your current HLA-specificities. HLA stands for human leukocyte antigen, which are proteins on the surface of cells. Your body may have developed antibodies against certain HLA types, which can make it harder to find a suitable donor organ.
The number of unacceptable HLA-specificities will be determined. These are HLA types that your immune system would likely reject.
Your memory B-cells will be analyzed. These are immune cells that remember previous exposures and can produce antibodies. The samples will be tested to see which HLA types these cells can target.
Your BAFF levels in the blood will be measured. BAFF is a protein that helps B-cells survive.
Different types of B-cell subsets in your blood will be counted and analyzed.
Specific B-cell populations will be collected for genetic analysis to understand how these cells function.
Step 3
Treatment phase with belimumab
You will receive belimumab treatment for 4 weeks. Belimumab is a medication that affects B-cells in your immune system.
The medication will be administered as a subcutaneous injection, meaning it will be injected under the skin.
The product used is Benlysta 200 mg solution for injection in pre-filled syringe.
During these 4 weeks, you will receive regular injections according to the treatment schedule.
Throughout the treatment period, you will be monitored for any adverse events, which are unwanted or harmful reactions to the medication.
Step 4
Assessments after 4 weeks of treatment
Blood samples will be collected again to measure changes in your HLA-specific memory B-cells.
The analysis will determine whether the number of HLA-specificities targeted by antibodies from your memory B-cells has changed compared to baseline.
The levels of antibodies in your blood plasma will be measured to see if they have changed.
Your BAFF levels will be measured again.
B-cell subsets in your blood will be analyzed again to identify any changes.
B-cell populations will be collected again for genetic analysis.
Step 5
Follow-up assessment at 12 weeks after treatment
Blood samples will be collected to assess your HLA-specific memory B-cells.
The analysis will show whether any changes observed at 4 weeks have been maintained or have changed further.
Monitoring for adverse events will continue during this period.
Step 6
Follow-up assessment at 36 weeks after treatment
Blood samples will be collected to assess your HLA-specific memory B-cells.
B-cell subsets in your blood will be analyzed.
B-cell populations will be collected for genetic analysis.
This assessment will show the longer-term effects of the treatment on your immune system.
Step 7
Delisting assessment and transplant matching evaluation
The number of unacceptable HLA-specificities will be reassessed to determine if any can be removed from your list.
Your vPRA (virtual panel reactive antibody) will be recalculated. This is a measure of how many potential donors you would react against.
The frequency of matching donors available for you within the Eurotransplant region will be calculated using online tools.
This evaluation will determine whether your chances of receiving a suitable transplant have improved.
Step 8
Extended safety monitoring
You will continue to be monitored for adverse events until 84 days after the end of treatment.
Any serious adverse events will be monitored for 40 weeks after the end of treatment.
If you receive a kidney transplant during or after the study, specific outcomes will be tracked, including rejection episodes, development of donor-specific antibodies (antibodies against the transplanted organ), graft loss, or mortality.

Who can join the trial?

6 criteria

You must be an adult between 18 and 75 years old
You must be a candidate for a kidney transplant, which means you are waiting to receive a donated kidney to replace a kidney that is not working properly
You must be highly-sensitized, which means your immune system has developed many antibodies that make it very difficult to find a matching donor organ. This is measured by having a 2% or less chance of finding a matching donor through the standard kidney allocation system, or a 0.5% or less chance through a special matching program
You must have given your informed consent, which means you understand the study and agree to take part in it
You must be willing and able to follow all the requirements and procedures of the study
If you are a woman, you must meet one of these conditions: have a negative pregnancy test at the beginning of the study and not be breastfeeding, or be unable to become pregnant due to surgery such as removal of the uterus or ovaries or having your tubes tied, or be past menopause which is when monthly periods have permanently stopped, or agree not to become pregnant during the study and use reliable birth control methods if you are able to become pregnant

Who cannot join the trial?

1 criterion

No specific exclusion criteria have been provided for this clinical trial in the available information.

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Responsive
Leids Universitair Medisch Centrum (LUMC)
Leiden, The Netherlands

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Investigated drugs

Belimumab is a medication that affects the immune system by targeting specific white blood cells called B-cells. In this trial, it is being used to help move memory B-cells from certain areas of the body into the bloodstream. This makes it easier for doctors to study these cells and better understand how the immune system might react to a transplant. The goal is to help highly-sensitized patients who are waiting for a transplant by improving how doctors assess their compatibility with potential donor organs.

Belimumab

What is already known about the treatment

Belimumab – Belimumab is a medication given through an injection into a vein (intravenous infusion) that is currently approved for treating autoimmune diseases and is being studied in clinical trials for preventing organ rejection in kidney transplant patients. It works by blocking a protein called BLyS that helps certain immune cells called B-cells survive, which reduces the number of antibodies that could attack a transplanted organ. In this research study, belimumab is being tested to help highly-sensitized transplant candidates by moving memory B-cells from lymph nodes into the bloodstream, making it easier to identify which donor organs they might safely accept. This medication belongs to a class of drugs called monoclonal antibodies that target specific parts of the immune system.

Investigated diseases

Antibody-mediated rejection of renal grafts
This is a condition where the body's immune system attacks a transplanted kidney through antibodies. These antibodies recognize the donor kidney as foreign tissue and trigger an immune response against it. The rejection occurs when antibodies bind to specific proteins on the blood vessels of the transplanted kidney, causing inflammation and damage. This process can happen at any time after the transplant, from days to years later. The antibodies involved are often directed against human leukocyte antigens, which are proteins that differ between the donor and recipient. Without proper management, this condition can lead to progressive damage of the transplanted kidney.
High HLA-immunization in transplant candidates
This condition occurs when a person waiting for an organ transplant has developed antibodies against many different human leukocyte antigens. These antibodies can form due to previous blood transfusions, pregnancies, or failed transplants. The presence of multiple antibodies makes it very difficult to find a compatible donor organ because the recipient's immune system will recognize and attack most available donor organs. Patients with this condition have a reduced chance of receiving a suitable transplant and often remain on waiting lists for extended periods. The level of sensitization is measured by the percentage of potential donors that would be incompatible with the recipient. This condition significantly limits transplant options and access to life-saving organ transplantation.