Evaluation of Long-Term Safety and Efficacy of Tegoprubart with Mycophenolate in Prophylaxis of Renal Allograft Rejection in Kidney Transplant Recipients

The primary objective of this study is to assess the long-term **safety** of tegoprubart 20 mg/kg administered intravenously, in combination with mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), in kidney transplant recipients. This evaluation is clinically relevant as it aims to ensure the sustained safety profile of tegoprubart, which is crucial for the prophylaxis of renal allograft rejection, a significant concern in post-transplant care.

Secondary objectives include:

• Assessing participant and graft survival at various timepoints in tegoprubart-treated participants compared to those treated with tacrolimus.
• Evaluating graft functional impairment at various timepoints in tegoprubart-treated participants compared to tacrolimus-treated participants.
• Assessing graft function as measured by estimated glomerular filtration rate (eGFR) in tegoprubart-treated participants compared to tacrolimus-treated participants.
• Determining the proportion of participants with biopsy-proven acute rejection (BPAR) at various timepoints in tegoprubart-treated participants compared to tacrolimus-treated participants, based on for-cause biopsies and central pathologist evaluation.

The clinical trial involves a total of **132 participants** who are being studied for the **prophylaxis of renal allograft rejection**. The study population includes both male and female subjects, with an age range that encompasses adults. Participants were selected based on their successful completion of a qualifying parent study and their ability to understand and consent to the study's key components. The trial does not include a vulnerable population. Participants are required to adhere to specific lifestyle considerations, such as agreeing not to participate in another interventional study while on treatment and using highly effective methods of contraception if of childbearing potential. The trial aims to assess the long-term safety of tegoprubart 20 mg/kg intravenous as part of a regimen with mycophenolate mofetil or mycophenolate sodium in kidney transplant recipients.

The clinical trial is designed as a **Phase 2, multicenter, open-label extension study** to evaluate the long-term safety and efficacy of Tegoprubart in kidney transplant recipients. The primary objective is to assess the long-term safety of Tegoprubart 20 mg/kg administered intravenously, in conjunction with mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), for the **prophylaxis of renal allograft rejection**. The trial is expected to conclude by February 28, 2030, with recruitment starting on March 19, 2025. Participants will be involved in the study for a maximum treatment period of 365 days.

The trial includes several key study visits. The initial visit, known as the inclusion or screening visit, will determine participant eligibility based on criteria such as successful completion of a qualifying parent study and the ability to provide informed consent. Follow-up visits will occur at regular intervals to monitor safety endpoints, including the incidence of treatment-emergent serious adverse events (TESAEs) and changes in vital signs and clinical laboratory measures. Efficacy endpoints will be assessed at 12, 24, 36, and 48 months, focusing on participant and graft survival, graft functional impairment, and the mean estimated glomerular filtration rate (eGFR). The end-of-study visit will finalize data collection and assess the overall outcomes of the trial.

Participants are expected to adhere to the study protocol, including the use of highly effective contraception methods for both male and female participants of childbearing potential. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or non-compliance with study procedures. The trial will utilize **Prograf** in various formulations, including hard capsules and concentrate for solution for infusion, as part of the treatment regimen. The study is not classified as a low-intervention trial and is conducted under the sponsorship of Astellas Pharma Co. Ltd. and Eledon Pharmaceuticals, Inc.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. The primary experimental medication is **AT-1501**, a monoclonal antibody, provided in a 190 mg vial for intravenous use. This medication is manufactured by Eledon Pharmaceuticals, Inc. using recombinant DNA technology in CHO cells. The maximum daily dose is 20 mg/kg, with a total maximum dose of 66 g over a treatment period of up to 365 days. The administration route is intravenous, and participant compliance will be monitored through regular assessments.

In addition to AT-1501, the trial includes the use of **Prograf** in various formulations as a comparator treatment. Prograf contains the active substance **tacrolimus**, a calcineurin inhibitor used to prevent organ transplant rejection. The formulations include 0.5 mg, 1 mg, and 5 mg hard capsules, as well as a 5 mg/ml concentrate for solution for infusion. All formulations are manufactured by Astellas Pharma Co. Ltd. The hard capsules are administered orally, while the concentrate is administered intravenously. The maximum daily dose for tacrolimus is 0.10 mg/kg, with a total maximum dose of 36.50 mg/kg over a treatment period of up to 12 months. Compliance with the dosing schedule will be monitored through regular follow-ups and assessments.

Participants in the trial may also receive standard-of-care therapy, including mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), as part of the treatment regimen. These medications are used in conjunction with the experimental and comparator treatments to assess the long-term safety and efficacy in kidney transplant recipients. The trial is designed to ensure rigorous monitoring of participant compliance and safety throughout the study duration.

The efficacy of the clinical trial will be assessed through several secondary endpoints, focusing on the long-term outcomes in kidney transplant recipients. The primary efficacy parameters include the proportion of participant and graft survival events, which will be evaluated at 12, 24, 36, and 48 months. These events are defined as the earliest occurrence of death, re-transplantation, or the requirement for regular dialysis. Additionally, the proportion of graft functional impairment will be assessed at the same timepoints, with impairment defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m².

Further efficacy assessments will include the mean eGFR at 12, 24, 36, and 48 months, as well as the proportion of participants experiencing biopsy-proven acute rejection (BPAR) at these intervals. A composite endpoint, consisting of graft failure, BPAR, or death, will also be evaluated at the specified timepoints. These efficacy parameters will be measured and analyzed using appropriate statistical methods to determine the long-term effectiveness of the treatment regimen in maintaining graft function and patient survival.