A Prospective, Open-label, Multicenter, Randomized Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Renal Allograft Recipients Aged 12 to Less Than 18 Years of Age to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications

The primary objective of this study is to evaluate the **patient and functional graft survival** in adolescent renal allograft recipients who are converted from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to a belatacept-based regimen. This evaluation will be conducted at least six months post-transplant and compared to recipients who continue on the CNI regimen, with assessments made at 24 months post-randomization. The clinical relevance of this objective lies in determining the potential benefits and risks associated with switching to a belatacept-based regimen, which may offer improved outcomes in terms of graft survival and patient adherence to immunosuppressive medications.

The clinical trial involves a total of **59 participants** who are adolescent recipients of renal allografts. The study population comprises both **male and female** subjects aged between **12 to less than 18 years**. Participants were selected based on specific criteria, including documented **EBV seropositivity** prior to transplant and randomization, and a stable regimen of a calcineurin inhibitor (CNI) with mycophenolate, with or without concomitant corticosteroids, for more than one calendar month prior to randomization. Additionally, participants were required to have stable renal function 12 weeks prior to screening, as assessed by the investigator and defined by protocol criteria for estimated glomerular filtration rate (eGFR) and proteinuria. The trial focuses on evaluating patient and functional graft survival in those converted from CNI to belatacept-based immunosuppression at least six months post-transplant, compared to those remaining on CNI at 24 months post-randomization. The study includes a vulnerable population, given the age range and medical condition of the participants.

The clinical trial is designed to evaluate the benefits and risks of converting adolescent renal allograft recipients from a calcineurin inhibitor (CNI)-based regimen to a **belatacept**-based immunosuppressive regimen. This study is a prospective, open-label, multicenter, randomized trial. Participants will be randomly assigned to either continue their current CNI-based regimen or switch to a belatacept-based regimen. The trial will span a duration of 24 months post-randomization, with the primary objective being the evaluation of patient and functional graft survival.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (12 to less than 18 years), documented EBV seropositivity, and stable renal function. Following randomization, participants will attend regular follow-up visits to monitor their health status, adherence to the immunosuppressive regimen, and any adverse events. The end-of-study visit will occur at the 24-month mark, where the primary endpoint, the proportion of participants with a functional graft and an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m², will be assessed.

The expected length of participant involvement is approximately 24 months, with conditions for early termination including significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide valuable insights into the long-term outcomes of belatacept-based immunosuppression in adolescent renal transplant recipients, potentially influencing future treatment guidelines.

The clinical trial involves the administration of several treatments, including **tacrolimus**, **belatacept**, and **ciclosporin**. **Tacrolimus** is provided in the form of granules for oral suspension. The maximum daily dose is 11 units, with a total maximum dose of 11 units over a treatment period of up to 24 months. The route of administration is oral, and the formulation is not specifically designed for pediatric use. The active substance, tacrolimus, is of chemical origin and is used as a comparator in the trial.

**Belatacept** is administered as a powder for solution for infusion. The maximum daily dose is 5 mg/kg, with a total maximum dose of 3600 mg/kg over a 24-month period. The route of administration is intravenous. Belatacept is the test product in this study and is produced by Bristol-Myers Squibb International Corporation. The active substance, belatacept, is also of chemical origin.

**Ciclosporin** is provided as an oral solution. The maximum daily dose is 250 units, with a total maximum dose of 250 units over a treatment period of up to 24 months. The route of administration is oral, and the formulation is not specifically designed for pediatric use. The active substance, ciclosporin, is of chemical origin and is used as a comparator in the trial.

Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the benefits and risks of converting adolescent renal allograft recipients to a belatacept-based immunosuppressive regimen compared to continuing a calcineurin inhibitor-based regimen.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of participants who survive with a functional graft and an estimated glomerular filtration rate (**eGFR**) greater than 30 mL/min/1.73 m², as calculated using the updated Schwartz formula, 24 months post-randomization. This endpoint will provide a measure of both patient survival and graft function over the specified period. The trial involves a comparison between adolescent renal allograft recipients converted from a calcineurin inhibitor (CNI) to a belatacept-based immunosuppressive regimen and those continuing on a CNI-based regimen. The efficacy assessment will be conducted at the 24-month mark following randomization, ensuring a comprehensive evaluation of the long-term benefits and risks associated with the treatment regimens under investigation.