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

87 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug abatacept for kidney transplant recipients?

A study showed that kidney transplant patients who couldn't tolerate certain standard drugs were successfully switched to abatacept, with all patients and their transplanted kidneys surviving for a median of 115 months. This suggests abatacept could be a promising alternative for those who can't use other common treatments. ^{1 2 3 4 5}

Is abatacept safe for kidney transplant patients?

Belatacept, a drug similar to abatacept, is used in kidney transplant patients and has been studied for safety. Some patients have successfully used abatacept when belatacept was unavailable, showing good long-term kidney function and survival, although there was one case of rejection. ^{1 2 3 4 6}

How is the drug abatacept different from other treatments for kidney transplant recipients?

Abatacept is unique because it can be administered subcutaneously (under the skin) rather than intravenously (through a vein), making it more convenient for patients. It is used as a rescue treatment for those who cannot tolerate calcineurin inhibitors, offering an alternative when belatacept is unavailable. ^{1 2 3 4 7}

What is the purpose of this trial?

This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function.The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.

Research Team

Idelberto R Badell, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation. [2023]

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

Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. [2022]

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

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

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

Belatacept in kidney transplantation. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Belatacept rescue conversion in kidney transplant recipients with vascular lesions (Banff cv score >2): a retrospective cohort study. [2023]

6. 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]

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

Overall Infectious Complications Related to Belatacept Conversion in Comparison to Tacrolimus in Kidney Transplant Recipients. [2022]