Evaluation of HLA-DR3DQ2 Influence on LADA Status and Immune Parameters Post Intralymphatic Glutamate Decarboxylase 2, Human, Recombinant Treatment

The primary objective of this study is to evaluate potential differences in the current **diabetes** status, specifically focusing on beta cell function and metabolic control, between carriers and non-carriers of **HLA-DR3DQ2**. This assessment is conducted three years following treatment with **GAD-alum** in the previous GADinLADA study. Understanding these differences is clinically relevant as it may provide insights into the long-term efficacy of GAD-alum treatment in individuals with Latent Autoimmune Diabetes in Adults (LADA) and the role of genetic factors such as HLA-DR3DQ2 in influencing treatment outcomes.

The clinical trial focuses on individuals diagnosed with **Latent Autoimmune Diabetes in Adults (LADA)**. The study population includes both male and female participants, with an age range that spans from 18 to 64 years. The trial does not involve a vulnerable population. Participants were selected based on their previous involvement in the GADinLADA study, as well as their consent to participate in this follow-up research. The sponsor has not provided the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include having signed informed consent and being a former participant in the GADinLADA study. The trial aims to assess differences in diabetes status between carriers and non-carriers of HLA-DR3DQ2, three years post-treatment with GAD-alum.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the long-term effects of treatment with GAD-alum on individuals with **Latent Autoimmune Diabetes in Adults (LADA)**. The primary objective is to assess differences in diabetes status, specifically beta cell function and metabolic control, between carriers and non-carriers of HLA-DR3DQ2, three years post-treatment. The trial is a follow-up to the previous GADinLADA study and is classified as a Phase 4 trial. The investigational product, Diamyd, is administered as a **suspension for injection** via intralymphatic use. The trial is expected to commence recruitment on May 1, 2024, and conclude by March 31, 2025.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed through signed informed consent and verification of prior participation in the GADinLADA study. The inclusion visit will also involve baseline assessments of diabetes status. Follow-up visits will be scheduled to monitor changes in beta cell insulin secretion capacity and metabolic control. The end-of-study visit will occur three years after the initial treatment, where final assessments will be conducted to compare with baseline and previous study endpoints.

The expected duration of participant involvement is approximately one year, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. Participants are required to adhere to the study protocol, and any deviation may also result in early termination. The trial aims to provide valuable insights into the long-term impact of GAD-alum treatment on LADA, contributing to the understanding of diabetes management in this patient population.

The clinical trial involves the administration of the experimental medication **Diamyd**, which is a **suspension for injection**. The active substance in Diamyd is **glutamate decarboxylase 2, human, recombinant**, a protein of non-human origin. The pharmaceutical form of Diamyd is specifically designed for **intralymphatic use**. The dosing regimen for this trial does not specify a maximum daily or total dose amount, indicating that the administration is likely based on a fixed schedule rather than a variable dosing strategy. The treatment period is limited to a maximum of one unit of time, as defined by the trial protocol. The medication is not formulated for pediatric use, and it is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the administration of Diamyd to assess its impact on diabetes status and immune parameters. Participant compliance with the dosing schedule will be monitored according to the trial's standard operating procedures, ensuring adherence to the intralymphatic administration route. The trial aims to evaluate the long-term effects of Diamyd, particularly in relation to the HLA-DR3DQ2 genetic marker, three years post-treatment.

Efficacy in this clinical trial will be assessed by evaluating changes in diabetes status variables, specifically focusing on **beta cell insulin secretion capacity** and metabolic control. These parameters will be measured three years after treatment with GAD-alum, compared to baseline and the end of the previous study, which was 12 months after baseline. The primary endpoint is the change in these diabetes status variables, providing insight into the long-term impact of the treatment on participants who were part of the GADinLADA study. The trial aims to determine possible differences in current diabetes status between carriers and non-carriers of HLA-DR3DQ2. The assessment will involve collecting and analyzing data on beta cell function and metabolic control to evaluate the sustained efficacy of the treatment over the specified period.