Evaluation of Lutikizumab Versus Adalimumab for Safety and Efficacy in Adults with Moderately to Severely Active Ulcerative Colitis

The primary objective of this multicenter, randomized study is to evaluate the **safety** and **efficacy** of **lutikizumab** compared to **adalimumab** in adult participants with moderately to severely active **ulcerative colitis**. This objective is clinically relevant as it aims to determine the potential of lutikizumab as an alternative therapeutic option for patients with this chronic inflammatory bowel disease, which can significantly impact quality of life and may lead to serious complications if not effectively managed.

The clinical trial involves a total of **132 participants** diagnosed with **ulcerative colitis**. The study population includes both male and female adults, with an age range of 18 to 64 years. Participants were selected based on their diagnosis of moderately to severely active ulcerative colitis, confirmed by a Modified Mayo Score of 5 to 9 points and a Mayo Endoscopic Subscore of 2 to 3. The trial does not include a vulnerable population. Participants have demonstrated an inadequate response, loss of response, or intolerance to at least one prior treatment, including oral aminosalicylates, corticosteroids, immunomodulators, or advanced therapies. The selection criteria ensure that the study population is representative of individuals who have experienced challenges with standard treatments for ulcerative colitis. Lifestyle considerations such as diet and physical activity were not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of **lutikizumab** compared to **adalimumab** in adult participants with moderately to severely active **ulcerative colitis**. This is a multicenter, randomized, double-blind, controlled study. The trial will involve a total duration of approximately 52 weeks, with the estimated recruitment start date set for August 26, 2024, and an estimated end date of April 26, 2027. Participants will be randomly assigned to receive either lutikizumab, adalimumab, or a placebo. The study will include several key visits: an initial screening visit to confirm eligibility, baseline visit for randomization, multiple follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes.

The inclusion criteria require participants to have a diagnosis of ulcerative colitis for at least 90 days prior to the baseline, with a Modified Mayo Score of 5 to 9 and a Mayo Endoscopic Subscore of 2 to 3. Participants must also have demonstrated an inadequate response or intolerance to at least one prior therapy. The primary endpoint is the percentage of participants achieving endoscopic improvement at week 12, with secondary endpoints including clinical remission and response per Modified Mayo Score, and endoscopic remission at the same time point.

Participants are expected to be involved in the study for the full 52-week duration unless early termination is warranted due to adverse events, lack of efficacy, or withdrawal of consent. The trial will adhere to rigorous safety monitoring protocols to ensure participant well-being throughout the study period. The study's design and procedures are structured to provide robust data on the comparative effectiveness of lutikizumab and adalimumab, contributing valuable insights into treatment options for ulcerative colitis.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The primary experimental medication is **Lutikizumab**, a biotechnological product with the active substance name **Lutikizumab**. It is administered as a **solution for injection** and a **solution for infusion**. The subcutaneous injection form is identified by the sponsor product code ABT-981 and is administered via **subcutaneous injection**. The intravenous infusion form is also identified by the sponsor product code ABT-981 and is administered via **intravenous infusion**. The maximum treatment period for Lutikizumab is 52 weeks, with no specified maximum daily or total dose amounts.

Another key medication used in the trial is **Adalimumab**, marketed under the name Humira. It is provided as a **solution for injection in pre-filled syringes** with dosages of 40 mg and 80 mg. The administration route is **subcutaneous**. The maximum daily dose is 160 mg, and the maximum total dose is 1200 mg over a treatment period of 52 weeks. Adalimumab is used as a comparator in the study to evaluate the efficacy of Lutikizumab.

The trial also includes the use of a **placebo** for Lutikizumab and a placebo for Adalimumab. These placebos are used to maintain blinding in the study and are not associated with any active substance. The pharmaceutical form and administration route for these placebos are not specified.

Additionally, **Sodium Chloride** is used as a non-experimental treatment in the trial. It is administered as a **solution for infusion** via **intravenous infusion**. Sodium Chloride serves as a chemical comparator in the study, with no specified maximum daily or total dose amounts, and is used over a treatment period of 52 weeks.

The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the percentage of participants who achieve endoscopic improvement at week 12. Secondary endpoints include the percentage of participants who achieve clinical remission per the Modified Mayo Score (mMS) at week 12, the percentage of participants who achieve clinical response per mMS at week 12, and the percentage of participants who achieve endoscopic remission at week 12. These endpoints are designed to evaluate the effectiveness of **lutikizumab** compared to **adalimumab** in adult participants with moderately to severely active ulcerative colitis.

The Modified Mayo Score (mMS) and Mayo Endoscopic Subscore (ESS) will be utilized as tools for measuring efficacy. The mMS is a validated scale that assesses disease activity in ulcerative colitis, while the ESS provides a specific evaluation of endoscopic findings. Efficacy assessments will be conducted at specific timepoints, with the primary and secondary endpoints being evaluated at week 12. The data collected will be analyzed to determine the proportion of participants meeting the criteria for improvement, remission, and response, providing a comprehensive assessment of the therapeutic impact of the investigational product.