Evaluation of Long-Term Efficacy and Safety of TEV-48574 in Adults with Moderate to Severe Ulcerative Colitis or Crohn's Disease

The primary objective of this study is to evaluate the **efficacy** of two different maintenance dose regimens of TEV-48574, administered subcutaneously every four weeks (Q4W), in adult patients with inflammatory bowel disease (IBD), specifically moderate to severe **ulcerative colitis** (UC) or **Crohn's disease** (CD). This evaluation is based on the maintenance of clinical remission in UC and endoscopic response in CD at the end of the maintenance period (EOM). The clinical relevance of this objective lies in its potential to inform treatment strategies that could improve long-term disease management and patient outcomes in these chronic conditions.

Secondary objectives include:

• Evaluating the efficacy of the two maintenance dose regimens of TEV-48574, as assessed by multiple standard measures at the end of the maintenance period (EOM).
• Assessing the immunogenicity of the two maintenance dose regimens of TEV-48574 in the same patient population.

The clinical trial involves a total of **70 participants** diagnosed with **Crohn's disease** or **ulcerative colitis**, focusing on individuals with moderate to severe forms of these conditions. The study population comprises adults, both male and female, without restrictions based on gender. Participants were selected based on their achievement of clinical response and/or clinical remission at specific points in a prior study or during the re-induction period of the current study. The age range of participants falls within categories 3 and 4, indicating a focus on adult populations. The trial does not include vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection criteria ensure that only those who have shown a response to previous treatments are included, thereby targeting a specific subset of the patient population for the evaluation of maintenance dose regimens of TEV 48574 administered subcutaneously every four weeks.

The clinical trial is a **Phase 2b**, randomized, double-blind, long-term extension study designed to evaluate the pharmacokinetics, efficacy, safety, and tolerability of TEV-48574 in adult patients with moderate to severe **ulcerative colitis** or **Crohn's disease**. The trial involves administering TEV-48574 as a **solution for injection** via subcutaneous use. The primary objective is to assess the efficacy of two different maintenance dose regimens of TEV-48574, administered every four weeks, by evaluating the maintenance of clinical remission in ulcerative colitis and endoscopic response in Crohn's disease at the end of the maintenance period. The trial is expected to conclude by February 17, 2031, with recruitment having commenced on August 1, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on clinical response or remission achieved in a prior dose-ranging study or during the re-induction period of this study. The maintenance period will include regular follow-up visits to monitor clinical outcomes and safety, with assessments conducted at specified intervals. The end-of-study visit will occur at week 44, where primary and secondary endpoints will be evaluated, including clinical remission and endoscopic response. The expected length of participant involvement is approximately 260 days, with conditions for early termination including adverse events or lack of clinical response.

Key endpoints include clinical remission based on a modified Mayo score for ulcerative colitis and a decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) for Crohn's disease. Secondary endpoints encompass clinical response, endoscopic improvement, and corticosteroid-free remission, among others. Safety assessments will include monitoring adverse events, laboratory test results, vital signs, and the presence of treatment-emergent anti-drug antibodies. Participants who discontinue the investigational product due to adverse events will also be documented. The trial is not classified as a low-intervention study and does not involve a pediatric formulation.

The clinical trial involves the administration of the experimental medication **TEV-48574**, which is a **solution for injection**. The active substance in TEV-48574 is **duvakitug**, a protein-based compound. The medication is administered via **subcutaneous use**. The dosing regimen for TEV-48574 involves a maximum daily dose of 900 mg and a maximum total dose of 2250 mg over a treatment period of up to 260 days. The administration frequency is every four weeks (Q4W), aligning with the study's objective to evaluate the efficacy of different maintenance dose regimens in adult patients with moderate to severe **ulcerative colitis** or **Crohn's disease**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the evaluation of TEV-48574. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed to assess the maintenance of clinical remission in ulcerative colitis and endoscopic response in Crohn's disease at the end of the maintenance period.

The efficacy of TEV-48574 in adult patients with moderate to severe **Ulcerative Colitis** (UC) or **Crohn's Disease** (CD) will be assessed through a series of primary and secondary endpoints. The primary endpoints include clinical remission for UC, defined by a modified Mayo score of ≤2 points with specific subscores, and endoscopic response for CD, indicated by a ≥50% decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) from the baseline of the dose-range finding study, both evaluated at week 44.

Secondary endpoints encompass a range of clinical and endoscopic measures. For UC, these include clinical response based on a modified Mayo score, endoscopic improvement and remission, and corticosteroid-free clinical remission. For CD, secondary endpoints include clinical response and remission based on the Crohn's Disease Activity Index (CDAI), corticosteroid-free endoscopic response, and corticosteroid-free clinical remission. Additionally, adverse events, treatment-emergent anti-drug antibodies (ADA), and neutralizing ADA in ADA-positive patients will be monitored throughout the study.

Efficacy assessments will be conducted at specified timepoints, with the primary focus on week 44. The modified Mayo score and SES-CD will be utilized as tools for evaluating clinical and endoscopic outcomes. The study aims to determine the effectiveness of two different maintenance dose regimens of TEV-48574 administered subcutaneously every four weeks, with the goal of maintaining clinical remission in UC and achieving endoscopic response in CD by the end of the maintenance period.