Evaluation of Dapirolizumab Pegol Efficacy and Safety in Moderately to Severely Active Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the ability of **dapirolizumab pegol (DZP)** as an add-on treatment to standard of care (SOC) medication to achieve clinically relevant long-term improvement of moderate to severe disease activity in patients with systemic lupus erythematosus (SLE). This is clinically significant as SLE is a chronic autoimmune disease characterized by periods of increased disease activity, and achieving sustained improvement can lead to better patient outcomes and quality of life.

Secondary objectives include evaluating the ability of DZP to:

• Achieve fast, clinically relevant improvement of moderate to severe disease activity.
• Achieve long-term control of disease activity.
• Achieve and maintain the treat-to-target goal: low disease activity with a low/acceptable corticosteroid dose over time.
• Achieve improvement of disease activity as measured by a numerical disease state score commonly used in clinical practice.
• Achieve components of the composite primary endpoints.
• Achieve alternative responder endpoints.
• Achieve endpoints supporting other key secondary endpoints.
• Evaluate the safety and tolerability of DZP as an add-on treatment to SOC medication.

The clinical trial involves a total of **347 participants** diagnosed with **systemic lupus erythematosus (SLE)**. The study population includes both male and female subjects, aged **16 years and older**, with no upper age limit specified. Participants were selected based on their moderate to severe disease activity, either due to persistent active SLE or frequent relapsing-remitting SLE, despite stable standard of care medication. The trial includes individuals with serological evidence of SLE, as demonstrated by specific autoantibodies or complement levels. Participants are required to be on stable doses of standard of care medications, which may include antimalarials, corticosteroids, and/or immunosuppressants. The trial population is considered vulnerable, and the selection process ensures that participants meet the necessary clinical criteria for inclusion. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **dapirolizumab pegol** in participants with moderately to severely active **systemic lupus erythematosus** (SLE). This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The trial will involve participants aged 16 years and older who meet specific inclusion criteria, including a diagnosis of SLE at least 24 weeks prior to the screening visit and evidence of moderate to severe disease activity. The study aims to assess the ability of dapirolizumab pegol as an add-on treatment to standard of care medication to achieve clinically relevant long-term improvement in disease activity.

The trial will span an estimated duration from September 2024 to March 2027. Participants will be involved in the study for a maximum treatment period of 48 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, baseline visits to establish disease activity levels, and follow-up visits at weeks 12, 24, and 48 to assess primary and secondary endpoints. The primary endpoint is the achievement of a British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) response at week 48. Secondary endpoints include BICLA responses at weeks 12 and 24, prevention of severe BILAG flares, and changes in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician's Global Assessment (PGA) scores.

Participants will be randomly assigned to receive either dapirolizumab pegol or a placebo, with both administered as a solution for infusion. The study is double-blind, meaning neither the participants nor the investigators will know which treatment is being administered. The expected length of participant involvement is up to 48 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial will monitor treatment-emergent adverse events, serious adverse events, and adverse events of special interest throughout the study duration.

The clinical trial involves the administration of **Dapirolizumab Pegol**, an experimental medication, as a **solution for infusion**. This biologic agent is administered via **intravenous use**. The maximum daily and total dose is 24 mg/kg, with a treatment period extending up to 48 weeks. The trial aims to evaluate the efficacy and safety of Dapirolizumab Pegol in participants with moderately to severely active systemic lupus erythematosus. The pharmaceutical form is specifically designed for infusion, and compliance with the dosing schedule is monitored throughout the study.

In addition to the experimental treatment, a **placebo** matching Dapirolizumab Pegol is used in the study. This placebo does not contain any active substance and serves as a control to assess the efficacy of the experimental drug. The placebo is administered in a manner consistent with the experimental treatment to maintain the study's double-blind design.

Several non-experimental treatments are also utilized in the study as part of the standard-of-care therapy. These include **Epinephrine**, classified under the ATC code C01CA24, with an unknown route of administration. The pharmaceutical form is denoted as PHF00231MIG. Additionally, **Glucocorticoids** (ATC code H02AB) and **Antihistamines for systemic use** (ATC code R06A) are included, both with unspecified routes and pharmaceutical forms labeled as PHF00231MIG and PHF00082MIG, respectively.

Other auxiliary treatments include **Immunosuppressants** (ATC code L04A) and **Antimalarials** (ATC code P01B), both with unknown routes of administration and pharmaceutical forms PHF2355 and PHF00245MIG, respectively. Furthermore, a combination of **Anhydrous Caffeine, Paracetamol DC, and Paracetamol Ph. Eur.** is used, classified under ATC code N02BE01, with an unspecified route and pharmaceutical form PHF00245MIG.

Lastly, **Diphenhydramine Hydrochloride, Zinc Oxide, and Camphor** are included as part of the auxiliary treatments, classified under ATC code D04AA32. The route of administration is unknown, and the pharmaceutical form is PHF00017MIG. These non-experimental treatments are administered according to standard clinical practice, and participant compliance is monitored to ensure adherence to the study protocol.

The efficacy of dapirolizumab pegol in the treatment of moderately to severely active **Systemic Lupus Erythematosus** (SLE) will be assessed through a series of predefined endpoints. The primary endpoint is the achievement of a British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) response at Week 48. Secondary endpoints include the achievement of BICLA response at Weeks 24 and 12, prevention of severe BILAG flares through Week 48, and achievement of Low Lupus Disease Activity State (LLDAS) in at least 50% of post-baseline visits through Week 48. Additional secondary endpoints involve changes from baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician's Global Assessment (PGA) at Week 48, as well as the achievement of SLE Responder Index 4 (SRI 4) response at Week 48.

Data collection will occur at multiple time points, including Weeks 12, 24, and 48, to evaluate the efficacy parameters. The BILAG 2004 and SLEDAI-2K are validated scales used to measure disease activity, while the PGA provides a clinician's assessment of the patient's overall disease status. The trial will also monitor the time to severe and moderate/severe BILAG flares through Week 48. The percentage of participants experiencing treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs of special interest or special monitoring will be recorded throughout the study to assess safety alongside efficacy.