Long-term Safety and Tolerability Evaluation of Itepekimab in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease

The primary objective of this study is to evaluate the long-term **safety** and tolerability of itepekimab in participants with moderate to severe **Chronic Obstructive Pulmonary Disease (COPD)** who have previously participated in itepekimab COPD clinical studies (EFC16750, EFC16819). This is clinically relevant as it aims to ensure that prolonged use of itepekimab does not result in adverse effects, thereby supporting its potential as a viable long-term treatment option for COPD, a condition characterized by persistent respiratory symptoms and airflow limitation.

Secondary objectives include:

• Evaluating the pharmacokinetic (PK) profile of itepekimab in these participants, which is crucial for understanding the drug's absorption, distribution, metabolism, and excretion over time.
• Assessing the immunogenicity of itepekimab, which involves determining the potential for the drug to provoke an immune response, an important factor in the long-term use of biologic therapies.
• Evaluating the long-term efficacy of itepekimab through various endpoints, which will provide insights into the sustained therapeutic benefits of the drug in managing COPD symptoms and improving patient outcomes.

The clinical trial involves a total of **475 participants** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their completion of the treatment period in a previous itepekimab COPD Phase 3 clinical study, specifically EFC16750 or EFC16819, with an end-of-treatment visit occurring no later than three days before the enrollment visit of this study. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The primary objective is to evaluate the long-term safety and tolerability of itepekimab in individuals with moderate to severe COPD. The sponsor has not provided additional information regarding the general health status or specific lifestyle factors of the participants.

The clinical trial is designed to evaluate the long-term safety and tolerability of **itepekimab** in patients with moderate to severe **Chronic Obstructive Pulmonary Disease (COPD)** who have previously participated in the EFC16750 or EFC16819 studies. This study is a randomized, double-blind, controlled trial involving the administration of itepekimab or a matched placebo. The trial is expected to commence on April 24, 2024, and conclude by December 1, 2026, with a maximum treatment period of 52 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the completion of a prior itepekimab COPD Phase 3 clinical study. The primary endpoint of the trial is the incidence of treatment-emergent adverse events (AEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and AEs leading to permanent treatment discontinuation. Secondary endpoints include the measurement of functional itepekimab concentrations in serum, incidence of treatment-emergent anti-drug antibody responses, and various changes from baseline in lung function and quality of life scores.

The sequence of study visits includes regular follow-up visits to monitor the safety and efficacy of the treatment, with assessments of lung function and collection of blood samples for pharmacokinetic and immunogenicity analyses. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as the occurrence of significant adverse events or withdrawal of consent.

The clinical trial involves the administration of **Itepekimab**, an experimental medication, to evaluate its long-term safety and tolerability in patients with moderate to severe chronic obstructive pulmonary disease (COPD). **Itepekimab** is a **solution for injection in a pre-filled syringe** and is administered via the **subcutaneous route**. The active substance, **itepekimab**, is a protein-based compound classified as an **anti-interleukin-33 IgG4 human monoclonal antibody**. The maximum daily dose of **itepekimab** is 300 mg, with a total maximum dose of 7800 mg over a treatment period of up to 52 weeks. The dosing schedule and participant compliance are monitored throughout the study to ensure adherence to the protocol.

The study also includes a **matched placebo** for the test product, which serves as a comparator treatment. The placebo is designed to mimic the experimental medication in appearance and administration method, ensuring the study remains double-blinded. The placebo does not contain any active substance and is used to assess the efficacy and safety of **itepekimab** by providing a baseline for comparison. Participants receiving the placebo follow the same administration schedule as those receiving the experimental medication, and their compliance is similarly monitored to maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed through a series of secondary endpoints designed to evaluate the impact of **itepekimab** on patients with chronic obstructive pulmonary disease (COPD). The parameters for efficacy include functional itepekimab concentrations in serum, the incidence of treatment-emergent anti-drug antibody responses, and the annualized rate of moderate to severe acute exacerbations of COPD (AECOPD). Additionally, the trial will measure the time to first moderate-to-severe and severe AECOPD events.

Further efficacy assessments will involve changes from baseline in pre-bronchodilator (Pre-BD) and post-bronchodilator (Post-BD) forced expiratory volume in one second (FEV1), as well as changes in the St. George's Respiratory Questionnaire (SGRQ) total score and domain scores. The trial will also evaluate changes from baseline in the EQ-5D-5L single index score and EQ visual analogue scale (EQ-VAS), along with changes from Week 0 for the Cough and Sputum Assessment Questionnaire (CASA-Q).