A Two-Cohort, Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating the Efficacy and Safety of Vixarelimab Compared with Placebo in Patients with Idiopathic Pulmonary Fibrosis and in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease

The primary objective of this study is to evaluate the **efficacy** of vixarelimab compared with placebo on lung function for each cohort. This is clinically relevant as it aims to determine the potential of vixarelimab to improve respiratory outcomes in patients with **Idiopathic Pulmonary Fibrosis** and **Systemic Sclerosis-Associated Interstitial Lung Disease**, conditions characterized by progressive lung damage and impaired lung function.

Secondary objectives include:

• Evaluating the efficacy of vixarelimab compared with placebo for each cohort.
• Assessing symptoms and quality of life of patients treated with vixarelimab compared with placebo for each cohort.
• Evaluating the safety of vixarelimab compared with placebo for each cohort.
• Assessing the safety of longer-term treatment with vixarelimab for each cohort.
• Characterizing the pharmacokinetics of vixarelimab for each cohort.
• Evaluating the immune response to vixarelimab for each cohort.

The clinical trial involves a total of **196 participants** diagnosed with either **Idiopathic Pulmonary Fibrosis** or **Systemic Sclerosis-Associated Interstitial Lung Disease**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, such as a forced vital capacity (FVC) of at least 45% predicted, a FEV1/FVC ratio greater than 0.70, and a diffusion capacity of the lung for carbon monoxide (DLCO) between 30% and 90% of predicted values. Additionally, participants must be able to complete a minimum 6-minute walk test distance of 150 meters while maintaining an oxygen saturation of over 83%. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **Vixarelimab** in patients with **Idiopathic Pulmonary Fibrosis** and **Systemic Sclerosis-Associated Interstitial Lung Disease**. The trial is structured into two cohorts, each focusing on one of the aforementioned conditions. The primary objective is to assess the impact of Vixarelimab on lung function, with the primary endpoint being the absolute change from baseline to Week 52 in forced vital capacity (FVC) measured in milliliters. Secondary endpoints include changes in the 6-minute walk test (6MWT) distance, percentage of predicted FVC, and diffusion capacity of the lung for carbon monoxide (DLCO), among others.

The trial is expected to last until April 2026, with participant recruitment starting in November 2023. Participants will be involved in the study for a maximum treatment period of 104 weeks. The study visits are sequenced as follows: an initial screening visit to confirm eligibility based on criteria such as FVC and DLCO levels, followed by regular follow-up visits to monitor progress and collect data on primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The study will utilize a solution for injection form of Vixarelimab, administered via subcutaneous injection. The trial will adhere to rigorous standards to ensure the integrity and reliability of the data collected, contributing valuable insights into the treatment of these complex pulmonary conditions.

The clinical trial involves the administration of **Vixarelimab**, an experimental medication, which is provided in the form of a **solution for injection**. The active substance in Vixarelimab is a protein of other origin, specifically designed for subcutaneous injection. The pharmaceutical form is a solution, and the administration route is subcutaneous. The dosing schedule is not explicitly detailed in the provided data, but the maximum treatment period is specified as 104 weeks. The product is identified by the sponsor product code RO 762-2888/F01-01 and is manufactured by Genentech, Inc. Participant compliance with the dosing regimen will be monitored throughout the study period.

In addition to the experimental treatment, the study includes a **placebo** group, which will receive the Vixarelimab Placebo. The placebo is designed to match the experimental medication in appearance and administration route, which is also a subcutaneous injection. The placebo serves as a comparator to evaluate the efficacy and safety of Vixarelimab in patients with idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease. The placebo is not associated with any active substance and is used to maintain the double-blind nature of the study.

The efficacy of Vixarelimab in the clinical trial will be assessed by evaluating its impact on lung function in patients with **Idiopathic Pulmonary Fibrosis** and **Systemic Sclerosis-Associated Interstitial Lung Disease**. The primary endpoint for efficacy is the absolute change from baseline to Week 52 in forced vital capacity (FVC) measured in milliliters. Secondary endpoints include the absolute change from baseline to Week 52 in the 6-minute walk test (6MWT) distance, percentage of predicted FVC, and diffusion capacity of the lung for carbon monoxide (DLCO). Additional secondary endpoints involve time to disease progression, time to first acute exacerbation of interstitial lung disease, changes in quantitative lung fibrosis on high-resolution computed tomography (HRCT) scans, and survival as measured by all-cause mortality.

Other secondary endpoints specific to Cohort 2 include changes in skin sclerosis measured by the modified Rodnan skin score (mRSS), and changes in pruritus measured by the 5-D Itch Scale total score. Health-related quality of life will be assessed using the King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire, while changes in cough and dyspnea will be evaluated using the Living with Pulmonary Fibrosis (L-PF) Symptoms domain scores. The incidence and severity of adverse events will be monitored, with severity determined according to the Division of AIDS (DAIDS) toxicity grading scale. Additionally, serum concentration of Vixarelimab and prevalence of anti-drug antibodies (ADAs) will be measured at specified timepoints to further assess efficacy and safety.