Evaluation of Anti-CD38 (Daratumumab) and CTLA4-Ig (Belatacept) in Highly HLA-Sensitized Patients Awaiting Kidney Transplantation

The primary objective of this study is to assess the **safety** and **efficacy** of dual targeting of peripheral and central humoral alloimmune memory using **anti-CD38 (Daratumumab)** and costimulation blockade with **CTLA4-Ig (Belatacept)** in highly HLA-sensitized patients who are awaiting kidney transplantation. This is clinically relevant as it addresses the challenge of managing patients with a calculated panel reactive antibody (cPRA) or transplant glomerulopathy index (TGI) of 95% or higher, who have been on the deceased donor kidney transplant waiting list without receiving a compatible donor offer for at least one year. The study aims to provide insights into potential therapeutic strategies that could improve transplant opportunities and outcomes for this patient population.

The clinical trial involves **patients** on the deceased donor kidney transplant waiting list with a calculated panel reactive antibody (cPRA) or transplant glomerulopathy index (TGI) of 95% or higher, who have not received a compatible donor offer for at least one year. The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. The trial does not specifically target a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status and lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is a **Phase 3** study designed to evaluate the safety and efficacy of dual targeting of peripheral and central humoral alloimmune memory using anti-CD38 (Daratumumab) and costimulation blockade with CTLA4-Ig (Belatacept) in highly HLA-sensitized patients awaiting kidney transplantation. This is a non-randomized, single-center pilot trial. The study is set to commence recruitment on January 19, 2022, and is expected to conclude by February 19, 2025. The trial targets patients with a calculated panel reactive antibody (cPRA) or transplant glomerulopathy index (TGI) of 95% or greater, who have been on the deceased donor kidney transplant waiting list without receiving a compatible donor offer for at least one year.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on the specified criteria. Following successful screening, participants will be enrolled in the study and will attend regular follow-up visits to monitor their response to the treatment and any potential adverse effects. The sequence and frequency of these visits will be determined by the study protocol to ensure comprehensive data collection and participant safety. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall outcomes of the intervention.

The expected duration of participant involvement in the trial will align with the overall study timeline, from the initial screening to the end-of-study visit. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, withdrawal of consent by the participant, or any other protocol-defined criteria that necessitate discontinuation. The study aims to provide valuable insights into the potential benefits and risks associated with the investigational treatment regimen for this specific patient population.

No specific information regarding the experimental medication, including its name, pharmaceutical form, dosage, route, and frequency of administration, is provided in the available data. Consequently, a detailed description of the experimental treatment cannot be formulated based on the current dataset.

Similarly, there is no information available about any non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatment, used in the study. Therefore, a description of these elements cannot be included.

Additional relevant information about drug administration, dosing schedules, and participant compliance monitoring is also not present in the provided data. As such, these aspects cannot be detailed in the current context.

The clinical trial is designed to assess efficacy in a Phase 3 study. The trial is scheduled to commence recruitment on January 19, 2022, with an estimated completion date of February 19, 2025. The efficacy assessment will be conducted through a series of predefined parameters, although specific endpoints and methods for measuring efficacy are not detailed in the available data. The trial will follow a structured protocol to ensure the collection and analysis of efficacy data is consistent and reliable. The study will adhere to rigorous standards typical of Phase 3 trials, focusing on evaluating the treatment's effectiveness in a larger population. The trial's design and execution will be aligned with clinical and regulatory requirements to ensure the validity and reliability of the efficacy outcomes.