Efficacy and Safety Evaluation of Namilumab in Patients with Chronic Pulmonary Sarcoidosis: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study

The primary objective of this study is to evaluate the effect of **namilumab** on the need for rescue treatment for worsening of chronic pulmonary sarcoidosis. This is clinically relevant as it aims to determine the potential of namilumab to reduce the frequency or necessity of additional interventions in managing disease exacerbations, thereby potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Evaluating the effect of namilumab on percent predicted forced vital capacity (ppFVC), which is a critical measure of lung function.
• Assessing the effect of namilumab on the time to the first rescue event, providing insights into its impact on disease progression.
• Determining the proportion of subjects achieving oral corticosteroid (OCS) taper without a rescue event, which could indicate a reduction in medication dependency.
• Assessing the effect of namilumab on respiratory symptoms based on the King's Sarcoidosis Questionnaire (KSQ) Lung domain, offering a patient-reported outcome measure of symptom relief.
• Evaluating the safety and tolerability of namilumab, ensuring the treatment's risk profile is acceptable for patients.

The clinical trial involves a total of **67 participants** diagnosed with **chronic pulmonary sarcoidosis**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their ability and willingness to provide written informed consent, as well as a documented history of sarcoidosis for at least six months, confirmed histologically. The trial includes individuals with a **Body Mass Index (BMI) of 40 kg/m² or less** at screening and those who have completed their primary series of COVID-19 vaccinations at least two weeks prior to randomization. The study population is characterized by a history of worsening sarcoidosis or increased pulmonary disease upon tapering of oral corticosteroids and/or immunosuppressive therapies. Participants are required to have evidence of sarcoidosis as indicated by high-resolution computed tomography (HRCT) consistent with pulmonary sarcoidosis and a Medical Research Council Dyspnea scale greater than 1. The trial does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** Phase 2 study with an open-label extension to assess the efficacy and safety of **Namilumab** in subjects with **chronic pulmonary sarcoidosis**. The trial aims to evaluate the effect of Namilumab on the need for rescue treatment for worsening of sarcoidosis. The study is expected to run from December 12, 2022, to July 20, 2025, with participants involved for a maximum treatment period of 50 weeks. The trial will include a screening visit, multiple follow-up visits, and an end-of-study visit.

Participants will be screened to ensure they meet the inclusion criteria, which include being 18 years or older, having a documented history of sarcoidosis, and having completed COVID-19 vaccinations. The primary endpoint is the proportion of subjects experiencing a rescue event during the double-blind period. Secondary endpoints include changes in percent predicted forced vital capacity, time to first rescue event, and safety assessments.

Study visits will be scheduled to monitor the participants' health and response to treatment. The inclusion visit will confirm eligibility, while follow-up visits will assess the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events or non-compliance with study protocols. Participants will receive either Namilumab or a placebo via subcutaneous injection, with the study maintaining blinding to ensure unbiased results.

The clinical trial involves the administration of **Namilumab**, a monoclonal antibody, as the experimental medication. Namilumab is provided in the form of a **solution for injection** and is administered via **subcutaneous injection**. The dosing regimen for Namilumab includes a maximum daily dose of 150 mg, with a total maximum dose of 2100 mg over the course of the treatment period, which spans up to 50 weeks. The active substance in Namilumab is derived from a protein of other origin, and the product is manufactured by Kinevant Sciences GmbH. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** as a non-experimental treatment to serve as a comparator. The placebo is utilized in a double-blind manner to assess the efficacy and safety of Namilumab in subjects with chronic pulmonary sarcoidosis. The placebo is administered in a manner consistent with the experimental treatment to maintain the integrity of the study design. The use of a placebo allows for a controlled evaluation of the therapeutic effects of Namilumab, minimizing bias and ensuring the reliability of the trial outcomes.

The efficacy of Namilumab in the treatment of **Chronic Pulmonary Sarcoidosis** will be assessed through a randomized, double-blind, placebo-controlled Phase 2 study with an open-label extension. The primary endpoint for evaluating efficacy is the proportion of subjects experiencing a rescue event during the double-blind (DB) period. Secondary endpoints include the change from baseline in percent predicted forced vital capacity (ppFVC) at Week 26, time to first rescue event during the DB period, and the proportion of subjects successfully achieving oral corticosteroid (OCS) taper without a rescue event during the DB period. Additionally, changes from baseline in the King's Sarcoidosis Questionnaire (KSQ) Lung domain score at Week 26 will be measured.

Safety and tolerability will also be assessed, including physical examinations, vital signs, electrocardiograms (ECGs), clinical laboratory measurements, and adverse events (AEs) during the DB period. The efficacy parameters will be collected and analyzed at specified timepoints, with particular attention to Week 26 for certain measures. The study aims to provide comprehensive data on the impact of Namilumab on the need for rescue treatment and overall disease management in subjects with Chronic Pulmonary Sarcoidosis.