Long-Term Safety and Tolerability Assessment of Dapirolizumab Pegol in Patients with Systemic Lupus Erythematosus: A Multicenter, Open-Label Extension Study

The primary objective of this study is to evaluate the long-term **safety** and tolerability of dapirolizumab pegol (DZP) treatment in participants with systemic lupus erythematosus (SLE). This is clinically relevant as it aims to ensure that the therapeutic use of DZP is safe for prolonged periods, which is crucial for managing a chronic condition like SLE.

Secondary objectives include evaluating the ability of DZP treatment to: - Prevent relevant disease flares - Achieve and maintain the treat-to-target goal of low lupus disease activity state (LLDAS) - Maintain long-term clinical response. These objectives are significant as they focus on the efficacy of DZP in controlling disease activity and sustaining clinical benefits over time, which are essential for improving patient outcomes in SLE management.

The clinical trial involves a total of **510 participants** diagnosed with **systemic lupus erythematosus (SLE)**. The study population includes both male and female subjects, with an age range encompassing young adults to older adults. Participants were selected based on their potential to benefit from long-term treatment with dapirolizumab pegol (DZP) and must have completed one of the parent studies within four weeks prior to entry into this study. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data. The primary objective of the trial is to evaluate the long-term safety and tolerability of DZP treatment in this diverse cohort.

The clinical trial is designed to evaluate the long-term safety and tolerability of **dapirolizumab pegol** in participants with **systemic lupus erythematosus**. This is a multicenter, open-label extension study, which follows a non-randomized, controlled design. The trial is expected to last until April 2029, with participant recruitment having commenced in September 2021. The study involves a series of visits, beginning with an inclusion visit, followed by regular follow-up visits, and concluding with an end-of-study visit. The inclusion visit serves to screen participants who have completed a parent study within four weeks prior to entry and are deemed by the investigator to potentially benefit from long-term treatment with dapirolizumab pegol.

Participants will be involved in the study for a maximum treatment period of 104 weeks. During this time, they will receive the investigational product via **intravenous use**. Follow-up visits are scheduled to monitor the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs, as well as to assess the achievement of secondary endpoints such as the prevention of severe BILAG flares and the achievement of BICLA response at specified intervals. The end-of-study visit will evaluate the overall safety and tolerability outcomes. Conditions that may lead to early termination from the study include the occurrence of TEAEs leading to permanent discontinuation of dapirolizumab pegol. The trial's primary endpoints focus on the incidence of TEAEs, while secondary endpoints include the prevention of severe flares and achievement of low disease activity states.

The clinical trial involves the administration of **Dapirolizumab pegol**, an experimental medication, to evaluate its long-term safety and tolerability in participants with Systemic Lupus Erythematosus. Dapirolizumab pegol is provided as a **solution for infusion** and is administered via the **intravenous route**. The dosage is set at 24 mg/kg, with a maximum treatment period of 104 weeks. This investigational drug is a protein-based therapeutic developed by UCB Biopharma SRL.

In addition to the experimental treatment, several non-experimental medications are included in the study. **Epinephrine**, also known as **adrenaline tartrate**, is classified under the ATC code C01CA24. It is a small molecule drug with an unspecified pharmaceutical form and route of administration. The maximum treatment period for this medication is 1 day.

Another non-experimental treatment is a combination of **anhydrous caffeine** and **paracetamol**, classified under the ATC code N02BE01. This small molecule drug is also provided in an unspecified pharmaceutical form and route of administration, with a maximum treatment period of 1 day.

**Diphenhydramine hydrochloride**, combined with **zinc oxide** and **camphor**, is included as a non-experimental treatment. It is classified under the ATC code D04AA32. This small molecule drug is provided in an unspecified pharmaceutical form and route of administration, with a maximum treatment period of 1 day.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study does not specify the exact pharmaceutical forms or routes of administration for the non-experimental treatments, indicating that these details are not critical to the primary objective of evaluating the safety and tolerability of Dapirolizumab pegol.

The efficacy of dapirolizumab pegol in the treatment of **Systemic Lupus Erythematosus** will be assessed through several secondary endpoints. These include the achievement of prevention of severe BILAG flares, with assessments conducted at multiple timepoints: Week 24, Week 52, and Week 104. Additionally, the study will evaluate the achievement of LLDAS (Lupus Low Disease Activity State) at 50% or more of all visits. The BICLA (British Isles Lupus Assessment Group-based Composite Lupus Assessment) response will also be measured at Week 24, Week 52, and Week 104. These efficacy parameters will be collected and analyzed to determine the long-term effectiveness of the treatment.