Adaptive Phase 2a/2b Randomized Double-Blind Placebo-Controlled Trial of LY3871801 in Adults with Moderately-to-Severely Active Rheumatoid Arthritis

The primary objective of this adaptive Phase 2a/2b, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of LY3871801 in adult participants with moderately-to-severely active **Rheumatoid Arthritis**. In Phase 2a, the efficacy will be assessed by changes in DAS28-hsCRP, a measure of disease activity, which is clinically relevant for determining the therapeutic impact on inflammation and joint function. In Phase 2b, the study aims to evaluate the efficacy of LY3871801 in achieving ACR50, a criterion indicating a 50% improvement in the number of tender and swollen joints, as well as other relevant clinical parameters. This objective is crucial for understanding the potential of LY3871801 to provide significant clinical benefits in managing Rheumatoid Arthritis.

The clinical trial involves a total of **270 participants** diagnosed with **Rheumatoid Arthritis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically includes adults and older 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 specifically target a vulnerable population. No specific lifestyle considerations such as diet, physical activity, or habits are highlighted in the selection criteria. The trial aims to evaluate the efficacy of LY3871801 compared to placebo, focusing on changes in DAS28-hsCRP and achieving ACR50.

The clinical trial is designed as an **adaptive Phase 2a/2b, randomized, double-blind, placebo-controlled** study to evaluate the efficacy of **LY3871801** in adult participants with moderately-to-severely active **rheumatoid arthritis**. The trial will assess the investigational product, LY3871801, administered in tablet form, compared to a matching placebo. The primary objective in Phase 2a is to evaluate the efficacy of LY3871801 compared to placebo as measured by changes in the Disease Activity Score – high-sensitivity C-reactive protein (DAS28-hsCRP). In Phase 2b, the focus shifts to evaluating the efficacy of LY3871801 in achieving a 50% improvement in the American College of Rheumatology criteria (ACR50). The trial is expected to commence recruitment on August 15, 2023, and conclude by July 15, 2026, with a maximum treatment period of 24 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility, which requires a diagnosis of adult-onset rheumatoid arthritis for at least three months. Following randomization, participants will attend regular follow-up visits to monitor efficacy and safety outcomes, including assessments of DAS28-hsCRP and ACR50 criteria. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted. The expected length of participant involvement is up to 24 weeks, contingent upon adherence to the study protocol. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial is not categorized as low intervention, as it involves a non-authorized investigational medicinal product, LY3871801, to investigate its safety and efficacy.

The clinical trial involves the administration of **LY3871801**, an experimental medication developed by Eli Lilly and Company Limited. **LY3871801** is formulated as a **tablet** and is intended for oral administration. The active substance, also named **LY3871801**, is of chemical origin. The trial is designed to evaluate the efficacy of this compound in adult participants with moderately-to-severely active rheumatoid arthritis. The maximum treatment period for the administration of **LY3871801** is 24 weeks. The specific dosage and frequency of administration are not detailed in the provided data, and the maximum daily and total dose amounts are indicated as zero, suggesting that these parameters are to be determined within the trial protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the **LY3871801** tablet in appearance but does not contain any active substance. The placebo serves as a control to assess the efficacy of **LY3871801** by providing a baseline for comparison. The placebo is also administered over a maximum treatment period of 24 weeks. The route of administration for the placebo is not explicitly stated, but it is implied to be oral, consistent with the form of the experimental medication.

The efficacy of LY3871801 in the treatment of moderately-to-severely active **Rheumatoid Arthritis** will be assessed in a randomized, double-blind, placebo-controlled clinical trial. The trial is divided into two phases: Phase 2a and Phase 2b. In Phase 2a, efficacy will be evaluated by measuring changes from baseline in the Disease Activity Score using high-sensitivity C-reactive protein (DAS28-hsCRP). This score is a widely used parameter in clinical trials to assess the activity of rheumatoid arthritis. In Phase 2b, the primary endpoint will be the percentage of participants achieving the American College of Rheumatology 50% improvement criteria (ACR50), which is a standard measure of clinical response in rheumatoid arthritis trials.