Abatacept Conversion for Kidney Transplant Recipients

Overseen By Idelberto R Badell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must be taking: Belatacept, Mycophenolate, Prednisone

Disqualifiers: Repeat transplant, Pregnancy, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals who have had a kidney transplant can safely switch from monthly belatacept infusions to weekly abatacept injections without compromising kidney function. It compares kidney health between two groups: one continuing with belatacept and the other starting abatacept (also known as Orencia, an immunosuppressant). The trial seeks participants who had their first kidney transplant at least two years ago, are currently using belatacept, and are considered low risk for immune issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in kidney transplant care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, participants must be on certain immunosuppressive medications like belatacept, mycophenolate mofetil, or azathioprine, and prednisone at specific doses to be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abatacept is generally safe for kidney transplant patients. In studies where patients switched from other treatments to abatacept, it proved safe. Some reports even indicate that abatacept helped patients who experienced side effects from other medications.

Additionally, studies on similar groups have shown that using abatacept did not cause serious side effects. Patients tolerated it well, without major drops in kidney function.

Belatacept, another treatment under comparison, is already approved for kidney transplant patients and is considered safe.

Since this trial is in an early phase, previous research has demonstrated that these treatments are safe enough for further testing. Overall, both abatacept and belatacept appear to be safe options based on current data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about abatacept for kidney transplant recipients because it offers a unique mechanism of action compared to the standard options like calcineurin inhibitors. Abatacept is a fusion protein that works by selectively modulating the T-cell activation process, potentially reducing the risk of transplant rejection with fewer side effects. Unlike other treatments that can be harsh on the kidneys, abatacept's targeted approach may preserve kidney function better, making it a promising alternative for long-term transplant success.

What evidence suggests that this trial's treatments could be effective for kidney transplant recipients?

Research has shown that abatacept, which participants in this trial may receive, benefits kidney transplant patients who need to switch from other treatments. In one study, patients who switched to abatacept had a 100% survival rate for both themselves and their transplanted kidneys over an average of 115 months. Another study found that higher levels of abatacept after a transplant reduced the risk of acute graft-versus-host disease, a condition where the new organ attacks the body. The FDA has also approved abatacept to prevent this condition in various transplant situations, demonstrating strong survival rates. These findings suggest that abatacept could be a promising option for maintaining the health of kidney transplant recipients. Meanwhile, another group in this trial will receive belatacept as the control treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Idelberto R Badell, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had their first kidney transplant from a living or deceased donor at least two years ago, are on specific immunosuppressants including belatacept, and have stable kidney function. They shouldn't have severe rejection history, active infections, significant proteinuria, uncontrolled diabetes, or be pregnant.

Inclusion Criteria

No rejection of Banff grade IIB or greater

I haven't had any organ rejection episodes in the last 6 months.

Negative crossmatch (actual or virtual)

Exclusion Criteria

Recent history of clinically significant proteinuria (urinary protein/Cr ratio >1.0)

I am taking belatacept, but not at a 5 mg/kg dose.

BK viremia of greater then 4.3 DNA log copies/mL (greater than 20,000 copies/mL) within 3 months of randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are converted from belatacept IV infusions to abatacept subcutaneous injections and monitored for kidney function

24 months

Monthly visits for belatacept group, weekly injections for abatacept group with additional lab visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Belatacept

Trial Overview The study compares monthly intravenous infusions of belatacept with subcutaneous injections of abatacept in maintaining kidney function post-transplant. It's a phase 2b trial to see if patients can switch between these treatments without harming their new kidney.

How Is the Trial Designed?

Group I: Abatacept Group (Conversion Group) Experimental Treatment 1 Intervention

Participants will receive the following: * Abatacept 125 mg s.c. weekly * Safety labs every 2 weeks (months 0-3) then monthly (months 4-12) * Blood draws forPK atMonth 6, Month 12, and two random time points in between Month 6 and Month 12 for a total of four time points. * Blood draws for PD studies at baseline/Month0 and Month 6 fora total of two timepoints. * HLA labs at 6, 12 and 24 months * Basic chemistry panel (CP Basic) at each study visit per clinical protocol for efficacy analysis * Hemoglobin A1c at Screening visit * Urine pregnancy test via test kit for WOCP at screening * BK and CMV testing at 6, 12, and 24 months

Group II: Belatacept group (Control Group) Active Control 1 Intervention

Participants will receive the following: * Belatacept: 5 mg/kg i.v. monthly * Blood draws for PD studies at baseline/Month 0 and Month 6 fora total of two timepoints. * HLA labs at 6, 12 and 24 months * Basic chemistry panel (CP Basic) every 3 months per clinical protocol for efficacy analysis * Hemoglobin A1c at Screening visit * Urine pregnancy test via test kit for WOCP at Screening visit * BK and CMV testing at 6, 12, and 24 months

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

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]

In a study of 219 kidney transplant patients, converting to belatacept led to a significant increase in kidney function, with the estimated glomerular filtration rate improving from 32 to 38 mL/min, indicating its efficacy in real-life settings.

Converting to belatacept within the first 3 months post-transplantation was identified as a key factor for better kidney function outcomes, although 8.2% of patients experienced acute rejection episodes, suggesting that while generally safe, monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conversion to Belatacept in Maintenance Kidney Transplant Patients: A Retrospective Multicenter European Study. Darres, A., Ulloa, C., Brakemeier, S., et al.[2022]

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]

In a study of 9 kidney transplant recipients who could not tolerate calcineurin inhibitors, switching to abatacept as a rescue immunosuppressive therapy resulted in 100% patient and graft survival over a median follow-up of 115 months.

Patients maintained stable renal function while on abatacept for a median of 82 months, with only one episode of cellular rejection, suggesting that abatacept could be a viable alternative for patients intolerant to traditional immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation. Badell, IR., Karadkhele, GM., Vasanth, P., et al.[2023]

Converting from tacrolimus to belatacept in kidney transplant patients with stable low eGFR (< 40 mL/min) resulted in a significant improvement in eGFR, with an average increase of 11.0 mL/min compared to 4.8 mL/min in the control group over 4 months.

However, while the belatacept group showed a modest increase in kidney function, there was a higher incidence of acute rejection (16.7%) compared to the control group, indicating potential safety concerns with this conversion strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. Abdelwahab Elhamahmi, D., Heilman, RL., Smith, B., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9411423/

Abatacept Rescue Therapy in Kidney Transplant Recipients This letter reports on our experience with CNI conversion to self-administered subcutaneous abatacept in five patients who benefited from RT for 1.5–84 months.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522091997

Abatacept as rescue immunosuppression after calcineurin ... Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients ...

3. ashpublications.org ashpublications.org/blood/article/142/8/700/496372/Higher-abatacept-exposure-after-transplant

Higher abatacept exposure after transplant decreases acute ... In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease ...

4. amjtransplant.org amjtransplant.org/article/S1600-6135(25)00971-2/fulltext

Late Abatacept Conversion in Kidney Transplant ... Purpose: Immunosuppression with belatacept in kidney transplantation results in superior outcomes as compared to calcineurin inhibitors.

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease

FDA approves abatacept for prophylaxis of acute graft The OS rate at Day 180 after HSCT was 98% (95% CI: 78%, 100%) for patients who received abatacept in combination with CNI and MTX compared to 75 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05975450?term=NCT05975450&rank=1

Subcutaneous Abatacept in Renal Transplant Recipients This study is being done to answer these questions: Are weekly abatacept injections under the skin a safe and effective substitute for monthly belatacept ...