Efficacy and Safety Comparison of Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 with Insulin Aspart in Adults with Type 1 Diabetes

The primary objective of this study is to demonstrate the effect on **glycaemic control** of once-weekly insulin icodec in combination with insulin aspart in individuals with Type 1 Diabetes (T1D). This includes comparing the difference in change from baseline in HbA1c between once-weekly insulin icodec and once-daily insulin glargine, both in combination with insulin aspart, after 26 weeks of treatment to a non-inferiority limit of 0.3%. This is clinically relevant as achieving optimal glycaemic control is crucial in managing T1D and reducing the risk of complications associated with the disease.

Secondary objectives include comparing parameters of glycaemic control, safety, and patient-reported outcomes of once-weekly insulin icodec compared to once-daily insulin glargine, both in combination with insulin aspart, in participants with T1D. These secondary objectives aim to provide a comprehensive evaluation of the treatment's impact on patient health and quality of life.

The clinical trial involves a total of **635 participants** diagnosed with **Type 1 Diabetes**. The study population includes both male and female subjects, with an age range of 18 to 64 years. Participants were selected based on specific criteria, including a diagnosis of type 1 diabetes mellitus for at least one year prior to screening and treatment with multiple daily insulin injections for at least six months before screening. The trial does not include a vulnerable population. Participants are required to have an HbA1c level between 7.0% and 10.0% at screening, confirmed by central laboratory analysis. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensures that participants have the ability and willingness to adhere to the protocol, including performing self-measured plasma glucose profiles as judged by the investigator.

The clinical trial is designed to evaluate the efficacy and safety of **insulin icodec** administered once weekly compared to once-daily **insulin glargine** in combination with **insulin aspart** in adults with **Type 1 Diabetes**. This is a randomized, double-blind, controlled trial with a duration of 26 weeks. Participants will be randomly assigned to receive either the investigational product, **Awiqli 700 units/mL solution for injection in pre-filled pen**, or the comparator, **Lantus SoloStar 100 units/mL solution for injection in a pre-filled pen**. The primary endpoint is the change in HbA1c from baseline to week 26, with secondary endpoints including changes in time in range, hypoglycemic episodes, and body weight.

The study will commence with a screening visit to confirm eligibility based on criteria such as a diagnosis of **Type 1 Diabetes** for at least one year, prior treatment with multiple daily insulin injections, and specific HbA1c levels. Following successful screening, participants will be enrolled and undergo randomization. Study visits will occur at regular intervals to monitor safety, efficacy, and adherence to the protocol, including self-measured plasma glucose profiles. The end-of-study visit will occur at week 26, where final assessments will be conducted.

Participant involvement is expected to last for the entire 26-week period unless early termination is warranted. Conditions for early termination include significant protocol deviations, adverse events, or withdrawal of consent. The trial aims to demonstrate non-inferiority of once-weekly **insulin icodec** compared to once-daily **insulin glargine** in terms of glycemic control, with a non-inferiority margin set at 0.3% for HbA1c change. The trial is not classified as low intervention and is categorized as a Phase III clinical trial.

The clinical trial involves the administration of **Awiqli**, a 700 units/mL solution for injection in a pre-filled pen, containing the active substance **insulin icodec**. This experimental medication is classified under the ATC code A10AE, which denotes insulins and analogues, long-acting. The pharmaceutical form is a solution for injection, and it is administered subcutaneously. The administration device, known as the FlexTouch pen-injector, is a disposable, pre-filled, multi-dose pen capable of delivering 10 U/increment doses. The treatment period for this medication is set at a maximum of 26 weeks, with weekly dosing. Participant compliance is monitored through the use of the pre-filled pen, ensuring accurate dosing and administration.

The comparator treatment in this study is **Lantus SoloStar**, a 100 units/mL solution for injection in a pre-filled pen, containing the active substance **insulin glargine**. This medication is also administered subcutaneously and is classified under the ATC code A10AE04. The Lantus SoloStar pen is designed for once-daily administration, and like the experimental treatment, it is used over a maximum period of 26 weeks. The study aims to compare the efficacy and safety of once-weekly insulin icodec with once-daily insulin glargine, both in combination with insulin aspart, in adults with type 1 diabetes.

The efficacy of the clinical trial will be assessed by evaluating the effect of once-weekly **insulin icodec** in combination with insulin aspart on glycaemic control in adults with Type 1 Diabetes. The primary endpoint for efficacy assessment is the change in HbA1c levels from baseline at week 0 to week 26, measured in percentage points. This will determine the non-inferiority of insulin icodec compared to once-daily insulin glargine, both in combination with insulin aspart, with a non-inferiority margin set at 0.3%.

Secondary endpoints include various parameters measured using the CGM system, Dexcom G7, such as the change in time spent in the glucose range of 3.9–10.0 mmol/L (70–180 mg/dL), time spent below 3.0 mmol/L (54 mg/dL), and time spent above 10.0 mmol/L (180 mg/dL). Additionally, the number of severe hypoglycaemic episodes (level 3) and clinically significant hypoglycaemic episodes (level 2) will be recorded, with confirmation by a blood glucose meter. Other secondary endpoints include the mean total weekly insulin dose, changes in body weight, and changes in ITSQ and ADAQ total scores.