Belatacept Injection for Kidney Transplant

Overseen by Piotr Witkowski, MD PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Chicago

Must be taking: Proteasome inhibitors

Must not be taking: Investigational drugs, Live vaccines

Disqualifiers: Neuropathy, Heart disease, Liver disease, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to test if using belatacept and a proteasome inhibitor can help highly immune-sensitive kidney transplant patients find suitable donors. These medications work together to calm the immune system, making it easier to match patients with compatible donors. Belatacept is a medication approved by the US FDA in 2011 for preventing organ rejection in kidney transplant recipients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking investigational drugs, you must stop them at least 14 days before starting the study treatment.

What data supports the effectiveness of the drug Belatacept for kidney transplant patients?

Belatacept has been shown to be effective in preventing organ rejection in kidney transplant patients, with studies indicating it is as effective as cyclosporine in terms of patient and graft survival, and better in terms of kidney function and lower rates of new-onset diabetes and high blood pressure. ^{1 2 3 4 5}

Is Belatacept safe for kidney transplant patients?

Belatacept is generally well tolerated in kidney transplant patients, but serious side effects can include certain types of cancer and serious infections. It has been shown to have a lower risk of new-onset diabetes and better blood pressure and cholesterol levels compared to cyclosporine. ^{1 2 3 5 6}

How is the drug Belatacept different from other treatments for kidney transplant patients?

Belatacept is unique because it is a biological drug that helps prevent organ rejection in kidney transplant patients by specifically targeting and down-regulating T-cell responses, unlike traditional treatments that often rely on calcineurin inhibitors. It is administered through an injection and has been shown to result in better kidney function and lower rates of new-onset diabetes and high blood pressure compared to cyclosporine, a common alternative. ^{1 2 3 5 7}

Research Team

Piotr Witkowski, MD PhD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for highly sensitized kidney transplant candidates who are EBV IgG positive, have no active infections or allergies to the drugs being tested, and are not pregnant. They must be vaccinated against COVID-19 and hepatitis B, listed for a transplant at University of Chicago, and agree to use two contraception methods post-treatment.

Inclusion Criteria

You are currently on the waiting list for a kidney transplant at the University of Chicago Transplant Institute.

I have been fully vaccinated against COVID-19 for at least 2 weeks.

I have antibodies against the Epstein-Barr Virus.

Exclusion Criteria

My liver is severely damaged or not functioning well.

I have not received a live vaccine in the last 4 weeks.

I haven't had a heart attack in the last 6 months and my heart condition is stable.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Desensitization Treatment

Highly sensitized patients are treated with belatacept and proteasome inhibitor to decrease calculated Panel of Reactive Antibodies (cPRA) and find a suitable kidney donor

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment, including episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR)

1 year

Treatment Details

Interventions

• Belatacept (Immunosuppressant)

Trial Overview The study tests if belatacept combined with a proteasome inhibitor can safely help find suitable donors for patients with high HLA sensitivity needing a kidney transplant. It aims to increase the chances of successful transplantation.

Participant Groups

Group I: Patients treated with belatacept and proteasome inhibitor Experimental Treatment 1 Intervention

Highly sensitized patients will be treated with belatacept and proteasome inhibitor and monitored for decreasing calculated Panel of Reactive Antibodies (cPRA) and suitable kidney donor base don negative crossmatch

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Pete Salzmann

University of Chicago

Chief Executive Officer since 2018

MD from University of Chicago’s Pritzker School of Medicine, MBA from Stanford University’s Graduate School of Business

Anh Nguyen

University of Chicago

Chief Medical Officer

MD from Rutgers New Jersey Medical School, MBA from University of Chicago

Findings from Research

An accurate and precise assay for measuring belatacept serum concentrations was developed, showing a measurement range of 0.9-30 mg/L and high accuracy (91%-99%).

This assay was applied in a pharmacokinetic study involving 5 renal transplant recipients, allowing for the visualization of belatacept concentrations over time, which is crucial for optimizing immunosuppressive therapy post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Klaasen, RA., Egeland, EJ., Chan, J., et al.[2019]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

Belatacept is as effective as cyclosporine in preventing organ rejection in kidney transplant patients, with similar rates of patient and graft survival and acute rejection, while showing a significant advantage in reducing renal impairment after 12 months.

Patients treated with belatacept experienced fewer serious side effects, including lower rates of new-onset diabetes and better blood pressure and lipid levels compared to those on cyclosporine, indicating a potentially safer profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. Garnock-Jones, KP.[2016]

Belatacept is an effective immunosuppressant for kidney transplant recipients, showing noninferior patient and allograft survival compared to cyclosporine in Phase 3 trials, with improved kidney function over three years.

While belatacept may offer benefits like better renal function and cardiometabolic health, it carries a risk of higher early rejection rates and potential increased risk of posttransplant lymphoproliferative disease, particularly in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. Wojciechowski, D., Vincenti, F.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Does belatacept improve outcomes for kidney transplant recipients? A systematic review. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Conversion to Belatacept in Maintenance Kidney Transplant Patients: A Retrospective Multicenter European Study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. [2023]