Long-term Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Adults with Bullous Pemphigoid: An Open-label Extension Study

The primary objective of this study is to assess the long-term **safety** and tolerability of treatment with efgartigimod PH20 SC in participants with **Bullous Pemphigoid** (BP). This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use, which is crucial for managing a chronic condition like BP.

Secondary objectives include:

• To assess the long-term efficacy and durability of response with efgartigimod PH20 SC treatment in participants with BP.
• To evaluate the impact of efgartigimod PH20 SC treatment in reducing long-term glucocorticoid-associated toxicity in participants with BP.
• To evaluate the impact of efgartigimod PH20 SC treatment on quality of life (QoL) in participants with BP.
• To evaluate the pharmacodynamics (PD) and immunogenicity of efgartigimod PH20 SC in participants with BP.

The clinical trial involves a total of **63 participants** diagnosed with **Bullous Pemphigoid**, a chronic autoimmune skin disorder. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on their completion of the week 36 visit of a previous study, ARGX-113-2009, and their ability to provide informed consent and comply with protocol requirements. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Participants' lifestyle factors such as diet, physical activity, or habits are not specified. The study aims to assess the long-term safety and tolerability of treatment with efgartigimod PH20 SC in this population.

The clinical trial is designed to evaluate the long-term safety, tolerability, and efficacy of **efgartigimod alfa** PH20 SC in adult participants diagnosed with **bullous pemphigoid**. This study is an open-label extension of a previous trial, categorized as a Phase 3 therapeutic exploratory and confirmatory clinical trial. The trial employs a controlled design, with participants receiving the investigational product via subcutaneous injection. The trial is expected to span from March 2023 to September 2025, with participant involvement lasting up to 48 weeks.

Participants eligible for inclusion must have completed the week 36 visit of the preceding study ARGX-113-2009 and be capable of providing informed consent. They must also agree to adhere to contraceptive measures as outlined in the protocol. The primary endpoints focus on the incidence and severity of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), as well as the rate of treatment discontinuation due to safety concerns. Secondary endpoints include the proportion of participants achieving complete remission (CR) or partial remission (PR) under various conditions, duration of sustained remission, and incidence of relapse.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy parameters. The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or choose to withdraw consent. The study aims to provide comprehensive data on the long-term use of efgartigimod alfa PH20 SC in managing bullous pemphigoid, contributing valuable insights into its therapeutic potential and safety profile.

The clinical trial involves the administration of **ARGX-113**, a **solution for injection** containing the active substance **efgartigimod alfa**. This investigational medication is administered via **subcutaneous injection**. The maximum daily dose is 1000 mg, with a total maximum dose of 50000 mg over a treatment period of up to 48 weeks. The primary objective of the trial is to evaluate the long-term safety, tolerability, and efficacy of efgartigimod PH20 SC in adult participants diagnosed with **bullous pemphigoid**. The pharmaceutical form of ARGX-113 is a solution for injection, and it is not formulated for pediatric use. The active substance, efgartigimod alfa, is a protein of other origin, specifically a human monoclonal antibody fragment targeting the FcRn receptor.

In addition to the experimental treatment, the study includes a **placebo** comparator, referred to as **PBO PH20 SC**. The placebo is administered in the same manner as the investigational drug, via subcutaneous injection. The placebo is used to assess the efficacy and safety of the investigational product by providing a baseline for comparison. The placebo does not contain any active pharmaceutical ingredients and is designed to mimic the appearance and administration route of ARGX-113 to maintain the study's integrity and blinding.

Efficacy in the clinical trial will be assessed through a series of secondary endpoints designed to evaluate the therapeutic impact of **efgartigimod alfa** in adult participants with Bullous Pemphigoid. The primary focus will be on the proportions of participants achieving complete remission (CR) or partial remission (PR) under various conditions, such as while off oral corticosteroids (OCS) for at least 8 weeks, or while on minimal OCS therapy, defined as ≤0.10 mg/kg/day of prednisone or an equivalent dose of another OCS. Additionally, the study will measure the duration of sustained remission, the proportion of participants who experience a relapse, and the time to relapse.

Further efficacy assessments will include the incidence and severity of relapse, as well as changes in Bullous Pemphigoid Disease Area Index (BPDAI) activity scores, Investigator's Global Assessment for Bullous Pemphigoid (IGA-BP) scores, and itch Numeric Rating Scale (NRS) over time. The trial will also evaluate treatment failure rates and various quality of life measures, including EQ-5D-5L, Dermatology Life Quality Index (DLQI), and Autoimmune Bullous Disease Quality of Life (ABQoL) scores. Additionally, the study will track percent changes from baseline in anti-BP180 and anti-BP230 antibody levels, and the incidence and prevalence of anti-drug antibodies (ADA).