Evaluation of Efavaleukin Alfa for Induction Therapy in Moderately to Severely Active Ulcerative Colitis: A Phase 2 Randomized, Double-blind, Placebo-controlled Study

The primary objective of this study is to evaluate the effect of **efavaleukin alfa** on the induction of clinical remission in subjects with moderately to severely active **ulcerative colitis**. This is clinically relevant as achieving clinical remission is a critical goal in the management of ulcerative colitis, aiming to improve patient outcomes and quality of life.

Secondary objectives include:

• Evaluating the effect of efavaleukin alfa on the induction of clinical response.
• Assessing the induction of endoscopic remission.
• Determining the induction of symptomatic remission.
• Evaluating the effect as induction therapy on combined endoscopic and histologic remission.
• Assessing the change in histological score.
• Evaluating the safety and tolerability of efavaleukin alfa.

The clinical trial investigating the effects of **efavaleukin alfa** on the induction of clinical remission in patients with **Ulcerative Colitis (UC)** includes a total of 162 participants. The study population comprises both male and female subjects, aged between 18 and 79 years, with the exception of participants from South Korea, where the age range is 19 to 79 years. Participants were selected based on a confirmed diagnosis of moderately to severely active UC, as evidenced by a modified Mayo score of 5 to 9 and a centrally read endoscopy score of at least 2. The trial excludes vulnerable populations and requires participants to have shown an inadequate response, loss of response, or intolerance to at least one conventional, biologic, or targeted small molecule therapy. Additionally, participants must maintain stable doses of specific medications, such as oral 5-aminosalicylates, corticosteroids, budesonide, beclomethasone dipropionate, and conventional immunomodulators, for a specified duration prior to enrollment. The trial does not impose specific lifestyle considerations regarding diet or physical activity.

The clinical trial is a **Phase 2**, dose-finding, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of efavaleukin alfa induction therapy in subjects with moderately to severely active **ulcerative colitis**. The primary objective is to assess the effect of efavaleukin alfa on the induction of clinical remission. The trial is expected to run from April 20, 2022, to May 27, 2026, with a primary endpoint of achieving clinical remission at week 12. Secondary endpoints include clinical response, endoscopic remission, symptomatic remission, combined endoscopic and histologic remission of colon tissue, change from baseline in histological score as measured by the Geboes score, and treatment-emergent adverse events, all evaluated at week 12.

Participants will be involved in the study for approximately 12 weeks, with the possibility of early termination if they do not meet the inclusion criteria or if they experience significant adverse events. The study begins with a screening visit to confirm eligibility, which includes a diagnosis of ulcerative colitis established at least three months prior to enrollment, a modified Mayo score of 5 to 9, and an inadequate response or intolerance to at least one conventional or biologic therapy. Participants must be aged 18 to 79 years, except in South Korea where the age range is 19 to 79 years. Following the screening, participants will be randomized to receive either the investigational product or placebo. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the overall outcomes of the treatment. Conditions for early termination include withdrawal of consent, protocol non-compliance, or the occurrence of serious adverse events that necessitate discontinuation of the study drug.

The clinical trial involves the evaluation of **efavaleukin alfa**, an experimental medication, for the induction of clinical remission in subjects with moderately to severely active **ulcerative colitis**. The investigational product, also known by its sponsor product code **AMG 592**, is developed by AMGEN INC. Efavaleukin alfa is a protein-based therapeutic agent, classified under the origin "Protein - Other". The pharmaceutical form, dosage, route, and frequency of administration are not specified in the provided data. The trial aims to assess the safety and efficacy of this agent in achieving clinical remission.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this randomized, double-blind, placebo-controlled study. The placebo is administered to a control group to evaluate the true efficacy of efavaleukin alfa by comparison. The specific details regarding the pharmaceutical form, dosage, and administration route of the placebo are not detailed in the available information. The study design ensures that neither the participants nor the investigators are aware of the treatment assignments, maintaining the integrity of the trial results.

The efficacy of efavaleukin alfa induction therapy in subjects with moderately to severely active **Ulcerative Colitis** will be assessed through a series of predefined endpoints. The primary endpoint is the achievement of clinical remission at week 12. Secondary endpoints include clinical response, endoscopic remission, symptomatic remission, and combined endoscopic and histologic remission of the colon tissue, all evaluated at week 12. Additionally, changes from baseline in histological score at week 12 will be measured using the Geboes score. Treatment-emergent adverse events will also be monitored as part of the secondary endpoints.

Data collection will occur at specified timepoints, with the primary and secondary endpoints being assessed at week 12. The use of validated scales and laboratory tests will ensure the accuracy and reliability of the efficacy assessments. The trial is designed as a randomized, double-blind, placebo-controlled, multicenter study, which will facilitate a robust evaluation of the treatment's efficacy in inducing clinical remission in the target population.