Efficacy and Safety Evaluation of Subcutaneous Belimumab in Systemic Sclerosis-Associated Interstitial Lung Disease: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the efficacy of **belimumab** compared to placebo, in addition to standard therapy, on reducing the decline in lung volume in participants with diffuse cutaneous systemic sclerosis-associated interstitial lung disease (dcSSc-ILD). This is clinically relevant as preserving lung function is crucial in managing dcSSc-ILD, a condition that can lead to significant morbidity and mortality due to progressive lung involvement.

Secondary objectives include:

• Evaluating the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing the extent of skin thickening in participants with dcSSc-ILD at Week 52.
• Assessing the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing fatigue in participants with dcSSc-ILD.
• Evaluating the efficacy of belimumab compared to placebo, in addition to standard therapy, on systemic sclerosis progression or mortality in participants with dcSSc-ILD.

The clinical trial involves a total of **177 participants** diagnosed with **systemic sclerosis associated interstitial lung disease** (dcSSc-ILD). The study population includes both male and female subjects aged **18 years or older**. Participants were selected based on specific criteria, including a documented diagnosis of systemic sclerosis as defined by the ACR/EULAR 2013 classification criteria, and the presence of diffuse cutaneous disease with interstitial lung involvement. The trial does not focus on a vulnerable population, and participants are required to have the capability to self-administer the study medication or have a caregiver who can assist. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to evaluate the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing the decline in lung volume, as measured by the change from baseline in forced vital capacity (FVC).

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study designed to evaluate the efficacy and safety of **belimumab** administered subcutaneously in adults with **systemic sclerosis associated interstitial lung disease** (SSc-ILD). The primary objective is to assess the efficacy of belimumab, in addition to standard therapy, in reducing the decline in lung volume, as measured by the change from baseline in forced vital capacity (FVC) over a period of 52 weeks. The trial is expected to commence recruitment on January 5, 2024, and conclude by July 30, 2027.

Participants will be involved in the study for a maximum of 52 weeks. The trial will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis of SSc, and presence of interstitial lung disease; regular follow-up visits to monitor safety and efficacy parameters; and an end-of-study visit to assess the final outcomes. The inclusion criteria require participants to be 18 years or older, have a documented diagnosis of SSc, and meet specific health conditions, including the ability to self-administer the study medication or have a caregiver who can do so.

Participants will be randomly assigned to receive either belimumab or a placebo, both administered as a solution for injection in pre-filled syringes. The study will employ a double-blind design, ensuring that neither the participants nor the investigators know which treatment is being administered, thus minimizing bias. The primary endpoint is the absolute change from baseline in FVC at Week 52, with secondary endpoints including changes in modified Rodnan skin score (mRSS), FACIT-Fatigue score, and time to SSc progression or death.

Participant involvement may be terminated early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial is not classified as a low-intervention study and is categorized as a Phase II/III therapeutic exploratory and confirmatory trial. The study aims to provide valuable insights into the potential benefits of belimumab for individuals with SSc-ILD, contributing to the understanding and management of this condition.

The clinical trial involves the administration of **Belimumab**, marketed under the name Benlysta, which is a **solution for injection** in a pre-filled syringe. The pharmaceutical form is specifically designed for subcutaneous administration. Each syringe contains a concentration of 200 mg/mL of the active substance, **Belimumab**, which is a protein-based therapeutic agent. The maximum daily dose and total dose amount are both set at 200 mg/mL. The treatment period extends up to 52 weeks. The product is manufactured by GlaxoSmithKline (Ireland) Limited and is identified by the marketing authorization number EU/1/11/700/006. The administration schedule and participant compliance are monitored throughout the study to ensure adherence to the dosing regimen.

The study also includes a **placebo** comparator, which is formulated to match the Belimumab solution for injection in terms of appearance and administration method. The placebo is administered subcutaneously at the same frequency and dosage as the active treatment to maintain the double-blind nature of the trial. The placebo is specifically designed to ensure that any observed effects can be attributed to the active substance, Belimumab, rather than other variables. Compliance with the placebo administration is similarly monitored to ensure the integrity of the study results.

The efficacy of belimumab in the clinical trial will be assessed by evaluating its impact on reducing the decline in lung volume in participants with **systemic sclerosis associated interstitial lung disease (SSc-ILD)**. The primary endpoint for efficacy evaluation is the absolute change from baseline in Forced Vital Capacity (FVC) measured in milliliters at Week 52. This parameter will provide a quantitative measure of lung function and its preservation over the course of the study.

Secondary endpoints include the absolute change from baseline in the modified Rodnan Skin Score (mRSS) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score, both assessed at Week 52. Additionally, the time to progression of systemic sclerosis or death will be monitored. These secondary endpoints will offer insights into the broader impact of belimumab on skin involvement and fatigue, as well as overall disease progression.

The trial is designed as a Phase 2/3, randomized, double-blind, placebo-controlled, parallel-group study. Efficacy assessments will be conducted at specified timepoints, with the primary endpoint evaluated at the end of the 52-week treatment period. The use of validated scales and measurements ensures the reliability and accuracy of the data collected throughout the trial.