Efficacy and Safety of Anti-T Lymphocyte Immunoglobulin in Recent Onset Type 1 Diabetes in Pediatric and Young Adult Populations: A Randomized, Double-Blind Study

The primary objective of this study is to assess the **efficacy** and safety of two different dosages of ATLG (anti-T lymphocyte immunoglobulin for human use, rabbit) in the treatment of patients with recent onset **Type 1 diabetes**. This is clinically relevant as it aims to prevent the loss of residual beta cell function, which is crucial in managing the progression of Type 1 diabetes and reducing the need for exogenous insulin therapy.

Secondary objectives include evaluating the effects of ATLG on the need for insulin therapy and other markers of diabetes. Additionally, the study aims to assess the impact of ATLG treatment on the immune system and other biological markers, including T-cell populations and markers, as well as the T-cell repertoire. These secondary objectives are important for understanding the broader immunological effects of ATLG and its potential role in modifying the disease course in Type 1 diabetes.

The clinical trial involves a total of **80 participants** diagnosed with **Type 1 diabetes**. The study population includes both male and female subjects, with an age range corresponding to categories 2 and 3, which typically encompass adolescents and young adults. Participants were selected based on specific criteria, although the details of these criteria are not fully disclosed. The trial does not include a vulnerable population. General health status and lifestyle considerations such as diet, physical activity, or habits are not specified. The primary objective of the trial is to evaluate the efficacy and safety of two different ATLG dosages in treating patients with recent onset Type 1 Diabetes.

The clinical trial is designed to evaluate the **efficacy** and safety of two different dosages of anti-T lymphocyte immunoglobulin for human use, rabbit, in patients with recent onset **Type 1 diabetes**. This study is a randomized, double-blind, placebo-controlled trial, which aims to prevent the loss of residual beta cell function in children and young adults diagnosed within 12 weeks. The trial is expected to run until December 31, 2027, with recruitment starting on December 1, 2023. Participants will be involved in the study for a maximum treatment period of one month, with the total trial duration extending over several years to assess long-term outcomes.

The sequence of study visits begins with an inclusion (screening) visit to determine eligibility based on specific criteria. Following successful screening, participants will undergo a series of follow-up visits, including assessments at months 6, 12, and 24. These visits will involve evaluations such as the mixed meal tolerance test (MMTT) to measure stimulated C-peptide concentration, changes in fasting C-peptide, HbA1c levels, and fasting plasma glucose. The primary endpoint is the area under the curve (AUC) for the MMTT-stimulated C-peptide concentration-time curve at 12 months relative to baseline. Secondary endpoints include peak MMTT-stimulated C-peptide concentration and changes in HbA1c and insulin treatment over 12 months.

The end-of-study visit will conclude the participant's involvement, with data collected to assess the long-term impact of the treatment. Participants may be terminated early from the study if they experience adverse effects, fail to comply with the study protocol, or withdraw consent. The trial is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Grafalon**, a pharmaceutical product formulated as a **solution for infusion**. The active substance in Grafalon is **anti-T lymphocyte immunoglobulin for human use, rabbit**, which is a structurally diverse, blood-derived substance. This medication is provided as a concentrate for infusion solution, with a concentration of 20 mg/ml. The administration route is via infusion, and the dosing regimen includes a maximum daily dose of 4 mg, with a total maximum dose of 12 mg over the treatment period. The treatment duration is limited to a maximum of one week. Grafalon is manufactured by Neovii Biotech GmbH and is not a pediatric formulation.

The study is designed as a randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of Grafalon in preventing the loss of residual beta cell function in patients with recent onset **Type 1 Diabetes**. Participants will receive either the experimental medication or a placebo, which serves as the comparator treatment. The placebo is administered in the same manner as the experimental drug to maintain the study's blinding. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the **AUC0-2h** for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve (C-peptideAUC) at 12 months relative to baseline. This measurement will provide insight into the preservation of beta-cell function in patients with recent onset Type 1 Diabetes.

Secondary endpoints include the peak MMTT stimulated C-peptide concentration (C-peptidemax) at months 6, 12, and 24 relative to baseline, as well as changes in fasting C-peptide from baseline to months 6 and 12. Additional secondary measures involve changes in HbA1c from baseline to month 12, HbA1c levels at 12 and 24 months, and changes in fasting plasma glucose from baseline to month 12. The total insulin treatment administered over 12 months will be calculated as AUC (insulinAUC), and the total daily insulin dose per kg will be assessed at 1, 3, 6, and 12 months. The percentage of patients maintaining stimulated peak C-peptide levels will also be evaluated.