Efficacy and Safety Evaluation of Efgartigimod PH20 SC in Adults with Bullous Pemphigoid: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of efgartigimod PH20 SC in achieving sustained remission in the treatment of adult participants with **bullous pemphigoid** (BP). This is clinically relevant as bullous pemphigoid is a chronic autoimmune blistering skin disease, and achieving sustained remission can significantly improve patient outcomes and quality of life.

Secondary objectives include: - Evaluating the corticosteroid-sparing effects of efgartigimod PH20 SC in participants with BP. - Characterizing the overall efficacy of efgartigimod PH20 SC in the treatment of participants with BP. - Evaluating the efficacy of efgartigimod PH20 SC in preventing relapse of BP. - Assessing the effect of efgartigimod PH20 SC on pruritus in participants with BP. - Assessing the safety and tolerability of efgartigimod PH20 SC administered to participants with BP. - Evaluating glucocorticoid-associated morbidity and the impact of efgartigimod PH20 SC on reducing glucocorticoid toxicity. - Evaluating the effects of efgartigimod PH20 SC on the quality of life (QoL) of participants with BP. - Evaluating the pharmacokinetics and pharmacodynamics of efgartigimod PH20 SC in participants with BP. - Evaluating the immunogenicity of efgartigimod PH20 SC in participants with BP. - Evaluating the competency of participants or caregivers to (self-) administer efgartigimod PH20 SC.

The clinical trial involves a total of **67 participants** diagnosed with **Bullous Pemphigoid (BP)**. The study population includes both male and female subjects who have reached the local legal age of consent. Participants are required to have clinical signs of BP and must be willing and able to understand the study requirements, provide written informed consent, and comply with the study protocol procedures. The age range of participants spans from adults to the elderly, as indicated by the age range categories provided. Both genders are included in the trial, and the population is considered vulnerable. Participants are expected to adhere to contraceptive measures consistent with local regulations, and women of childbearing potential must have negative pregnancy tests at screening and baseline. The selection of participants was based on their ability to meet these criteria, ensuring a representative sample of the BP patient population. Lifestyle considerations such as diet, physical activity, or habits were not specified by the sponsor.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study to evaluate the efficacy and safety of **efgartigimod alfa** in adult participants with **bullous pemphigoid**. The trial aims to achieve sustained remission in the treatment of this condition. The study is expected to last approximately 36 months, with an estimated recruitment start date of February 26, 2022, and an estimated end date of October 5, 2025.

Participants will be randomly assigned to receive either efgartigimod PH20 SC or a placebo. The trial will include several key visits: an initial screening visit to assess eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to evaluate the overall outcomes. The primary endpoint is the proportion of participants in complete remission while off oral corticosteroid therapy for at least eight weeks at week 36. Secondary endpoints include various measures of disease activity and quality of life, as well as the incidence of adverse events.

Participant involvement is expected to last up to 36 weeks, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or adverse events that necessitate discontinuation. The study will adhere to strict eligibility criteria, including the requirement for participants to provide informed consent, be of legal age, and have clinical signs of bullous pemphigoid. Women of childbearing potential must use contraceptive measures and have negative pregnancy tests at screening and baseline.

The clinical trial involves the administration of **efgartigimod alfa**, marketed under the name ARGX-113, as the experimental medication. This investigational product is provided in the form of a **solution for injection**. The active substance, efgartigimod alfa, is a protein of other origin. The administration route for ARGX-113 is via **subcutaneous injection**. The maximum daily dose is set at 1000 mg, with a total maximum dose of 38000 mg over a treatment period of up to 36 weeks. The trial aims to evaluate the efficacy of efgartigimod PH20 SC in achieving sustained remission in adult participants with bullous pemphigoid.

In addition to the experimental treatment, the study includes the use of **prednisone** as a non-experimental treatment. Prednisone is administered in the form of **tablets** for **oral use**. The active substance is of chemical origin. The dosing regimen for prednisone is based on body weight, with a maximum daily dose of 1 mg/kg and a total maximum dose of 252 mg/kg over a 36-week period. Prednisone serves as a standard-of-care therapy in the management of bullous pemphigoid.

The trial also incorporates a placebo control, identified as PBO PH20 SC. This placebo is utilized to maintain the double-blinded nature of the study. The pharmaceutical form and administration details for the placebo are not specified. The inclusion of a placebo group allows for a more rigorous assessment of the experimental treatment's efficacy and safety.

The efficacy of the investigational product, **efgartigimod PH20 SC**, in the treatment of **bullous pemphigoid** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants who achieve complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for at least 8 weeks by week 36. Secondary endpoints include the cumulative dose of OCS from baseline to week 36, the proportion of participants achieving an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1, and the proportion of participants who achieve control of disease activity (CDA) and remain free of relapse through week 36.

Additional secondary endpoints involve changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score, changes in itch scores from the Itch Numerical Rating Scale (NRS), and time to achieve various clinical milestones such as CDA and CR. The study will also evaluate the incidence and severity of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs). Furthermore, the study will monitor serum concentrations of efgartigimod, changes in total IgG serum levels, and the presence of antidrug antibodies (ADA) against efgartigimod and antibodies against rHuPH20.