Pan-European proof-of-concept study comparing Decentralised Clinical Trial (DCT) and hybrid approaches to conventional clinical trial approaches in patients with Type 2 diabetes mellitus treated with Toujeo®

The primary objective of this study is to evaluate the potential benefits of a **Decentralised Clinical Trial (DCT)** approach in patients with **Type 2 diabetes mellitus** treated with **Toujeo®** (insulin glargine 300 U/mL). The study aims to assess improvements in participant recruitment, retention, diversity, site and participant satisfaction, and cost-effectiveness. Additionally, it seeks to determine the acceptability of the DCT approach by measuring variables related to safety oversight, treatment adherence, and data quality, including missing data and query rate, within trial arms with varying degrees of decentralisation. These objectives are clinically relevant as they may enhance the efficiency and effectiveness of clinical trials, potentially leading to improved patient outcomes and resource allocation.

Secondary objectives include determining whether the efficacy of treatment with Toujeo® is within the accepted range across trial arms with different levels of decentralisation. This evaluation is crucial for ensuring that the decentralised approach does not compromise the therapeutic effectiveness of the treatment.

The clinical trial involves a total of **100 participants** diagnosed with **Type 2 diabetes mellitus (T2DM)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a diagnosis of T2DM for at least one year prior to the screening visit and a stable basal insulin regimen for a minimum of three months. The trial does not include a vulnerable population. Participants are required to have the mental and physical capacity to perform daily activities independently, including the administration of injectable insulin and monitoring of blood glucose levels. Additionally, they must have access to a tablet or smartphone with Bluetooth functionality and an internet connection to facilitate remote data entry and video conferencing. The trial does not impose specific lifestyle considerations such as diet or physical activity, focusing instead on the management of T2DM through insulin therapy.

The clinical trial is designed to evaluate the benefits and acceptability of **decentralized clinical trial** (DCT) and hybrid approaches compared to conventional clinical trial methods in patients with **Type 2 diabetes mellitus** (T2DM) treated with **Toujeo**. This study is a randomized, double-blind, controlled trial with an estimated duration of 24 months. The trial aims to assess the potential benefits of a DCT approach on participant recruitment, retention, diversity, site and participant satisfaction, and cost, as well as the acceptability of a DCT approach by measuring variables related to safety oversight, treatment adherence, and data quality.

Participants will be involved in the study for a maximum of 24 weeks. The trial will commence with a screening visit to confirm eligibility, which includes criteria such as a diagnosis of T2DM for at least one year, stable basal insulin treatment, and the ability to perform daily activities independently. Following the screening, participants will be randomized into different arms of the study, each with varying degrees of decentralization. Study visits will include baseline assessments, follow-up visits at Weeks 12 and 24, and an end-of-study visit to evaluate primary and secondary endpoints, such as changes in HbA1c and fasting SMPG levels.

Participants are expected to comply with study procedures, including home visits, remote data entry, and video conferencing, depending on the study arm. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or any adverse events that compromise participant safety. The trial is categorized as a low-intervention study, as the investigational medicinal product is an authorized medicine, and the procedures involved do not pose more than minimal additional risk compared to standard clinical practice.

The clinical trial involves the administration of **Toujeo 300 units/ml SoloStar**, a **solution for injection** in a pre-filled pen, as the experimental medication. The active substance in this formulation is **insulin glargine**, a long-acting insulin analog used in the management of **Type 2 diabetes mellitus**. The pharmaceutical form is a solution for injection, specifically designed for subcutaneous administration. The medication is provided in a pre-filled pen to facilitate ease of use and ensure accurate dosing. The administration route is subcutaneous injection, which is a common method for insulin delivery, allowing for gradual absorption into the bloodstream. The dosing schedule is determined by the investigator based on the individual needs of the participant, with a maximum treatment period of 24 months. The trial does not specify a maximum daily or total dose amount, indicating that dosing is tailored to the participant's requirements. Compliance with the dosing regimen is monitored throughout the study to ensure adherence and evaluate the effectiveness of the treatment.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the efficacy and acceptability of the **Toujeo** formulation in a decentralized clinical trial setting. The trial aims to assess various parameters, including participant recruitment, retention, diversity, site and participant satisfaction, and cost, as well as treatment adherence and data quality. The study does not involve any pediatric formulations, and the product is not classified as an orphan drug. The trial is conducted under the authorization of the European Union, with the marketing authorization held by **SANOFI-AVENTIS DEUTSCHLAND GMBH**. The trial's objective is to explore the potential benefits of a decentralized clinical trial approach compared to conventional methods in managing Type 2 diabetes mellitus with **Toujeo**.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints focus on operational aspects of the trial, such as the time to enrolment from site activation until the last participant is enrolled, the proportion of participants completing the study period, and various diversity aspects including race, ethnicity, and socioeconomic status. Additionally, the time from event occurrence to collection of adverse events (AE) or serious adverse events (SAE) in the eDiary or electronic case report form (eCRF) will be evaluated. Adherence to the daily insulin injection will be measured by analyzing the percentage of days with documented intake until the participant's end of treatment (EOT).

The secondary endpoints are centered on clinical outcomes related to **Type 2 diabetes mellitus** management. These include changes in HbA1c levels from baseline to Week 12 and Week 24, as well as changes in fasting self-monitored plasma glucose (SMPG) from baseline to the same time points. The percentage of participants achieving an HbA1c level of less than 7% (53 mmol/mol) and a fasting SMPG target of 80–130 mg/dL (4.4–7.2 mmol/L) at Week 12 and Week 24 will also be assessed. Furthermore, the percentage of participants reaching the target HbA1c level without severe and/or confirmed hypoglycemia will be evaluated.