J1A-MC-KDAF: A Phase 2b, Double-Blind, Placebo-Controlled Study to Evaluate Peresolimab in Adult Participants with Moderately-to-Severely Active Rheumatoid Arthritis

The primary objective of this Phase 2b, double-blind, placebo-controlled study is to evaluate the **efficacy** of peresolimab compared to placebo in achieving ACR20 in adult participants with moderately-to-severely active **Rheumatoid Arthritis**. ACR20 is a clinically significant measure indicating a 20% improvement in tender or swollen joint counts and other relevant clinical parameters, which is crucial for assessing the therapeutic benefit in patients with this chronic autoimmune condition.

The clinical trial involves a total of **351 participants** diagnosed with **Rheumatoid Arthritis**, a condition categorized under autoimmune and connective tissue diseases. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults. Participants were selected based on the principal inclusion criterion of having a diagnosis of adult-onset rheumatoid arthritis for at least three months. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The population includes vulnerable groups, indicating a careful selection process to ensure the safety and ethical treatment of all participants. The trial aims to evaluate the efficacy of peresolimab compared to placebo in achieving ACR20, a measure of improvement in rheumatoid arthritis symptoms.

The clinical trial is a **Phase 2b, double-blind, placebo-controlled study** designed to evaluate the efficacy of **peresolimab**, a humanised IgG1 monoclonal antibody against PD-1, in adult participants with moderately-to-severely active **rheumatoid arthritis**. The trial aims to compare the efficacy of peresolimab to a placebo in achieving a 20% improvement in the American College of Rheumatology (ACR) core set values, known as ACR20. The study is expected to run from March 13, 2023, to October 30, 2024, with a total duration of approximately 19 months.

Participants will be randomly assigned to receive either peresolimab or a placebo, administered via subcutaneous injection. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to assess the final outcomes. The inclusion criteria require participants to have a diagnosis of adult-onset rheumatoid arthritis for at least three months. The expected length of participant involvement is up to 60 weeks, depending on the treatment group assignment.

Conditions that may lead to early termination from the study include adverse reactions to the investigational product, non-compliance with study procedures, or withdrawal of consent by the participant. The trial is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants. The study's primary endpoint is the percentage of participants achieving ACR20, with no secondary endpoints specified. The investigational product, peresolimab, is provided as a solution for infusion, while the placebo is a sodium chloride solution for injection.

The clinical trial involves the administration of an **experimental medication** identified as LY3462817, which is a **humanised IgG1 monoclonal antibody against PD-1**. This investigational product is provided in the form of a **solution for infusion**. The administration route is via **subcutaneous injection**. The maximum daily dose is 36 mg, with a total maximum dose of 15,000 mg over a treatment period of 60 days. The medication is developed by Eli Lilly and Company and is not formulated for pediatric use. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study includes a **non-experimental treatment** using **sodium chloride** as a placebo. This is also provided as a **solution for injection** and administered via **subcutaneous injection**. The sodium chloride solution serves as a comparator to evaluate the efficacy of the experimental medication. The placebo does not have a specified maximum daily or total dose, and its administration is limited to a maximum treatment period of 12 days. The use of sodium chloride as a placebo is standard in clinical trials to maintain blinding and ensure unbiased results.

The efficacy of peresolimab in the treatment of moderately-to-severely active **Rheumatoid Arthritis** will be assessed in a Phase 2b, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the percentage of participants achieving a 20% improvement in the American College of Rheumatology core set values, known as ACR20. This endpoint is a widely recognized measure in clinical trials for rheumatoid arthritis, indicating a significant reduction in disease activity.

Participants will be monitored throughout the trial to determine the achievement of ACR20. The trial will compare the efficacy of peresolimab against a placebo, with the primary objective being to evaluate the difference in ACR20 achievement rates between the two groups. The trial is designed to ensure rigorous assessment of the investigational product's efficacy, adhering to established clinical trial protocols and standards.