Evaluation of Ixekizumab on Endogenous Insulin Preservation in Newly Diagnosed Type 1 Diabetes: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate whether **Ixekizumab**, compared with placebo, enhances residual insulin secretion in newly diagnosed patients with **type 1 diabetes**. This is measured by the stimulated C-peptide two-hour area under the curve profile during a Mixed Meal Tolerance Test. The clinical relevance of this objective lies in its potential to preserve endogenous insulin production, which could significantly impact the management and progression of type 1 diabetes.

Secondary objectives include assessing changes in various parameters such as:

• Mean insulin dosage per kilo body weight
• Time in range (3.9-10 mmol/l) and time in hypoglycemia (<3.9 mmol/l and <3.0 mmol/l) measured by masked continuous glucose monitoring (CGM)
• Difference in HbA1c levels
• Proinsulin/c-peptide ratio in serum as a measure of beta cell stress
• Time in glucose target (3.9-8 mmol/l) and time in hyperglycemia (>10 mmol/l and ≥14 mmol/l) measured by masked CGM
• Glycemic variability including standard deviation (SD), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE)
• Proportion of patients with peak residual insulin secretion measured by Mixed Meal Tolerance Test (MMTT): stimulated C-peptide >0.4 pmol/mL
• Well-being, treatment satisfaction, hypoglycemic confidence, and diabetes-related distress measured using respective validated questionnaires
• Physical activity measured using the International Physical Activity Questionnaire (IPAQ)

The clinical trial involves participants diagnosed with **Type 1 Diabetes** within 100 days prior to screening. The study population includes both male and female subjects aged 18 to 45 years. Participants are required to have a remaining stimulated peak C-peptide level of at least 0.20 nmol/L, with specific criteria for those aged 36-45 years. The trial does not include a vulnerable population. Participants must have antibodies to at least one of the following antigens: insulin/IAA, GAD-65, IA-2, or ZnT8. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the ability to comply with study requirements, including the use of reliable contraception methods for participants of childbearing potential. The trial does not impose specific lifestyle considerations such as diet or physical activity. The study population was selected based on these criteria to ensure the reliability and validity of the trial outcomes.

The clinical trial is designed to evaluate the efficacy of **ixekizumab** in preserving endogenous insulin production in individuals newly diagnosed with type 1 diabetes. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to last until December 31, 2028, with recruitment having commenced on September 1, 2022. Participants will be involved in the study for a maximum of 52 weeks, during which they will receive subcutaneous injections of either ixekizumab or a placebo, with the total treatment period not exceeding 12 months.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, recent diagnosis of type 1 diabetes, and presence of specific antibodies. Following successful screening, participants will undergo baseline assessments, including the Mixed Meal Tolerance Test (MMTT) to measure residual insulin secretion. Subsequent follow-up visits will occur at regular intervals to monitor changes in insulin secretion, insulin dosage, glucose levels, and other secondary endpoints. The primary endpoint is the change in residual insulin secretion, as measured by the stimulated C-peptide two-hour area under the curve profile from baseline to week 52.

The end-of-study visit will involve final assessments to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with the study protocol, or choose to withdraw consent. The trial's rigorous design and comprehensive follow-up aim to provide valuable insights into the potential benefits of ixekizumab for individuals with type 1 diabetes.

The clinical trial involves the administration of **Ixekizumab**, marketed under the name Taltz, which is provided as an 80 mg **solution for injection** in a pre-filled syringe. This experimental medication is administered via **subcutaneous injection**. The maximum daily dose is 160 mg, with a total maximum dose of 1440 mg over the course of the study. The treatment period is set for a maximum of 12 weeks. Ixekizumab is a protein-based therapeutic agent, specifically classified under the ATC code L04AC13. The pharmaceutical form is a solution for injection, and the product is manufactured by Eli Lilly and Company (Ireland) Limited. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** group, which receives a treatment identical in composition to the investigational medicinal product, except for the absence of the active substance, **Ixekizumab**. The placebo is used to provide a comparator for evaluating the efficacy of the experimental treatment. The placebo is administered in the same manner as the active treatment, ensuring blinding and maintaining the integrity of the study design. The placebo does not contain any active pharmaceutical ingredients and is intended to mimic the administration experience of the active treatment group.

The efficacy of Ixekizumab in preserving endogenous insulin production in newly diagnosed patients with type 1 diabetes will be assessed through a randomized, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change in residual insulin secretion, which will be measured by the stimulated C-peptide two-hour area under the curve profile using the Mixed Meal Tolerance Test (MMTT) from baseline to week 52. This measurement will provide insight into the ability of Ixekizumab to maintain insulin production compared to placebo.

Secondary endpoints include various parameters related to glucose control and insulin usage. These include changes in mean insulin dosage per kilogram of body weight over 24 hours, time spent with glucose levels within the target range (3.9-10 mmol/L), and time spent in hypoglycemia (<3.9 mmol/L), all measured from baseline to week 52 using masked continuous glucose monitoring (CGM) with the Libre Pro iQ device. Additional secondary endpoints involve changes in HbA1c levels, proinsulin/C-peptide ratio as a measure of beta-cell stress, and glycemic variability metrics such as standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE).

Patient-reported outcomes will also be assessed, including changes in WHO-5, DTSQs, DTSQc, HCS, PAID, and IPAQ scores from baseline to week 52. These assessments will provide a comprehensive evaluation of the impact of Ixekizumab on both physiological and quality-of-life measures in patients with type 1 diabetes. The trial will also evaluate these variables at specific time points, including baseline to week 4, week 13, and week 26, to monitor the progression and efficacy of the treatment over time.