Efficacy and Safety Evaluation of GSK3915393 in Idiopathic Pulmonary Fibrosis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this Phase 2, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of GSK3915393 in reducing the decline in lung volume in participants with **Idiopathic Pulmonary Fibrosis** (IPF). This is clinically relevant as IPF is characterized by progressive lung function deterioration, and interventions that can slow this decline are crucial for improving patient outcomes.

Secondary objectives include:

• Further evaluating the efficacy of GSK3915393 compared with placebo in reducing the decline in lung volume in IPF participants.
• Assessing the **safety** and tolerability of GSK3915393 compared with placebo in IPF participants.
• Evaluating the systemic exposure to GSK3915393 in IPF participants.

The clinical trial involves a total of **72 participants** diagnosed with **Idiopathic Pulmonary Fibrosis** (IPF). The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a diagnosis of IPF within the last five years and a Forced Vital Capacity (FVC) of at least 45% of the predicted normal. Additionally, the Diffusing Capacity for Carbon Monoxide (DLCO) must be at least 25% of the predicted normal, corrected for hemoglobin. Participants may be on a stable dose of antifibrotic medications such as nintedanib or pirfenidone, or there must be a valid reason for not receiving these treatments. The trial does not include vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, parallel group study designed to evaluate the efficacy and safety of GSK3915393 in participants with **Idiopathic Pulmonary Fibrosis (IPF)**. The primary objective is to assess the efficacy of GSK3915393 in reducing the decline in lung volume compared to placebo. The trial is expected to last approximately 26 weeks, with participant involvement beginning from the screening visit and continuing through to the end-of-study visit.

Participants will undergo a series of study visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of IPF within the last five years, a forced vital capacity (FVC) of at least 45% of predicted normal, and a diffusing capacity for carbon monoxide (DLCO) of at least 25% of predicted normal. Those on antifibrotic treatment must have been on a stable dose for at least 12 weeks prior to screening. The trial will include follow-up visits at Weeks 4, 8, 12, and 18, with assessments focusing on changes in FVC and monitoring for adverse events (AEs) and serious adverse events (SAEs).

The end-of-study visit will occur at Week 26, where the primary endpoint will be the absolute change from baseline in FVC (mL). Secondary endpoints include changes in FVC at various intervals and the incidence of AEs/SAEs. Participants may be withdrawn from the study early if they experience significant adverse effects or if they no longer meet the study criteria. The investigational product, GSK3915393, is administered orally in the form of a film-coated tablet, with a maximum daily dose of 160 mg and a total dose not exceeding 29,120 mg over the treatment period.

The clinical trial involves the administration of **GSK3915393**, an experimental medication, in the form of a **film-coated tablet**. The active substance, GSK3915393, is of chemical origin and is provided by GlaxoSmithKline. The medication is administered orally with a maximum daily dose of 160 mg and a total maximum dose of 29,120 mg over a treatment period of 26 weeks. The primary objective of the study is to evaluate the efficacy of GSK3915393 in reducing the decline in lung volume in participants with **Idiopathic Pulmonary Fibrosis** (IPF). Participant compliance with the dosing schedule will be monitored throughout the study.

The study also includes a **placebo** group, where participants receive a placebo designed to match the GSK3915393 tablet. The placebo is administered in the same pharmaceutical form and via the same oral route as the experimental medication. This placebo-controlled design allows for a comparison of the efficacy and safety of GSK3915393 against a non-active treatment, ensuring the reliability of the study results. The placebo is used to maintain the double-blind nature of the trial, where neither the participants nor the investigators are aware of the treatment assignments.

The efficacy of GSK3915393 in the treatment of **Idiopathic Pulmonary Fibrosis (IPF)** will be assessed through a Phase 2, randomized, double-blind, placebo-controlled, parallel group study. The primary endpoint for evaluating efficacy is the absolute change from baseline in Forced Vital Capacity (FVC) measured in milliliters at Week 26. Secondary endpoints include the absolute change from baseline in FVC at Weeks 4, 8, 12, and 18, as well as the percentage predicted change at Weeks 4, 8, 12, 18, and 26. Additionally, the proportion of participants achieving a relative decline from baseline in FVC of 5% or less at Week 26 will be evaluated.

Data collection will involve validated measurements of FVC at specified timepoints throughout the 26-week treatment period. The study will also monitor adverse events (AEs) and serious adverse events (SAEs) over the 26 weeks, alongside clinically important findings in vital signs, electrocardiograms, and laboratory tests including hematology, hepatobiliary, and clinical chemistry. These assessments will provide comprehensive data on the efficacy and safety of GSK3915393 in comparison to placebo in participants with IPF.