A Phase 3, Single-Arm, Multicenter, Open-label Extension of Study ARGX-113-2007 to Investigate the Long-term Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Participants Aged 18 Years and Older With Active Idiopathic Inflammatory Myopathy

The primary objective of this study is to assess the long-term **safety** and tolerability of efgartigimod PH20 SC in adult participants with active idiopathic inflammatory myopathy (IIM). This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use, which is crucial for managing chronic conditions like IIM.

Secondary objectives include:

• To assess the health impact of glucocorticoid use and evaluate the steroid-sparing effect of efgartigimod PH20 SC. This is important for reducing potential side effects associated with long-term glucocorticoid therapy.
• To observe the long-term efficacy of efgartigimod PH20 SC, which is essential for determining the sustained therapeutic benefits of the treatment in managing IIM.

The clinical trial involves a total of **160 participants** diagnosed with **Active Idiopathic Inflammatory Myopathy (IIM)**. The study population includes both male and female adults, with an age range that encompasses individuals from young adults to older adults. Participants were selected based on their completion of a prior study, ARGX-113-2007, 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 are required to adhere to contraceptive measures as per local regulations, with women of childbearing potential needing a negative pregnancy test at baseline. The study aims to assess the long-term safety and tolerability of efgartigimod PH20 SC in this specific patient group.

The clinical trial is designed as a **Phase 3**, single-arm, multicenter, open-label extension study to evaluate the long-term safety, tolerability, and efficacy of **efgartigimod alfa** in adult participants with active **idiopathic inflammatory myopathy**. The trial will involve the administration of efgartigimod alfa as a **subcutaneous** solution for injection. The study is expected to commence on September 21, 2023, and conclude by September 23, 2027, with an estimated duration of 52 weeks for each participant. Participants will be required to have completed a prior study, ARGX-113-2007, to be eligible for inclusion.

The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The primary endpoints will focus on the incidence and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events, as well as changes in vital signs, electrocardiogram, and laboratory parameters over time. Secondary endpoints will include measures such as the Composite Glucocorticoid Toxicity Index, prednisone dose reduction, and the proportion of participants achieving clinically inactive disease or remission.

Participant involvement is expected to last for the full duration of the study, approximately 52 weeks, unless early termination is warranted. Conditions that may lead to early termination include the occurrence of severe adverse events, non-compliance with study protocols, or withdrawal of consent. The study aims to provide comprehensive data on the long-term use of efgartigimod alfa in managing active idiopathic inflammatory myopathy, contributing valuable insights into its safety and efficacy profile.

The clinical trial involves the administration of **efgartigimod alfa**, marketed as ARGX-113, which is a **biological** agent. This investigational product is provided as a **solution for injection** and is administered via the **subcutaneous** route. The maximum daily dose is 143 mg, with a total maximum dose of 52,000 mg over a treatment period of 52 weeks. The primary objective of the trial is to assess the long-term safety and tolerability of efgartigimod PH20 SC in adult participants with active idiopathic inflammatory myopathy.

**Methotrexate** is utilized in the study in two pharmaceutical forms: a **solution for injection in pre-filled syringe** and a **tablet**. The injectable form is administered **subcutaneously**, while the tablet is taken **orally**. The maximum daily dose for both forms is 3.5 mg, with a total maximum dose of 1,500 mg over a 60-day treatment period. Methotrexate is a **chemical** compound used as an auxiliary treatment in the trial.

**Mycophenolate mofetil** is provided as a **film-coated tablet** and is administered **orally**. The maximum daily dose is 3,000 mg, with a total maximum dose of 1,269,000 mg over a 423-day treatment period. This **chemical** compound serves as an auxiliary treatment in the study.

**Dexamethasone** is administered as a **tablet** via the **oral** route. The maximum daily dose is 3 mg, with a total maximum dose of 1,296 mg over a 423-day treatment period. Dexamethasone is a **chemical** compound used as an auxiliary treatment.

**Mycophenolic acid** is available as a **gastro-resistant tablet** and is taken **orally**. The maximum daily dose is 3,000 mg, with a total maximum dose of 1,269,000 mg over a 423-day treatment period. This **chemical** compound is used as an auxiliary treatment in the trial.

**Hydrocortisone** is provided in **tablet** form and administered **orally**. The maximum daily dose is 80 mg, with a total maximum dose of 33,840 mg over a 423-day treatment period. Hydrocortisone is a **chemical** compound used as an auxiliary treatment.

**Prednisolone** is administered as a **tablet** via the **oral** route. The maximum daily dose is 20 mg, with a total maximum dose of 8,460 mg over a 423-day treatment period. Prednisolone is a **chemical** compound used as an auxiliary treatment.

**Leflunomide** is provided as a **film-coated tablet** and is taken **orally**. The maximum daily dose is 20 mg, with a total maximum dose of 8,460 mg over a 423-day treatment period. Leflunomide is a **chemical** compound used as an auxiliary treatment.

**Azathioprine** is available as a **film-coated tablet** and is administered **orally**. The maximum daily dose is 250 mg, with a total maximum dose of 105,750 mg over a 423-day treatment period. Azathioprine is a **chemical** compound used as an auxiliary treatment.

**Tacrolimus** is provided in **hard capsule** form and is taken **orally**. The maximum daily dose is 3 mg, with a total maximum dose of 1,269 mg over a 423-day treatment period. Tacrolimus is a **chemical** compound used as an auxiliary treatment.

**Hydroxychloroquine sulfate** is administered as a **film-coated tablet** via the **oral** route. The maximum daily dose is 600 mg, with a total maximum dose of 253,800 mg over a 423-day treatment period. Hydroxychloroquine sulfate is a **chemical** compound used as an auxiliary treatment.

**Betamethasone** is provided as a **tablet** and is taken **orally**. The maximum daily dose is 3 mg, with a total maximum dose of 1,269 mg over a 423-day treatment period. Betamethasone is a **chemical** compound used as an auxiliary treatment.

**Ciclosporin** is available in **soft capsule** form and is administered **orally**. The maximum daily dose is 400 mg, with a total maximum dose of 169,200 mg over a 423-day treatment period. Ciclosporin is a **chemical** compound used as an auxiliary treatment.

**Methylprednisolone** is administered as a **tablet** via the **oral** route. The maximum daily dose is 16 mg, with a total maximum dose of 6,768 mg over a 423-day treatment period. Methylprednisolone is a **chemical** compound used as an auxiliary treatment.

The efficacy of the clinical trial will be assessed using a range of primary and secondary endpoints. Primary endpoints include the incidence and severity of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) categorized by System Organ Class (SOC) and Preferred Term (PT) over time. Additionally, changes and abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters will be monitored throughout the study.

Secondary endpoints focus on various measures of disease activity and treatment impact. These include the Composite Glucocorticoid Toxicity Index (C-GTI), which comprises the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS) over time. The study will also evaluate prednisone dose reduction (average monthly dose) and the proportion of participants who discontinue corticosteroids at week 52. The Total Improvement Score (TIS) will be assessed over time, with the proportion of TIS responders (minimal, moderate, major) evaluated at weeks 12, 24, and 52. Individual core set measures (CSMs) of the TIS will also be tracked.

Further efficacy assessments include the percentage of participants with clinically inactive disease, defined as no evidence of disease activity based on a Physician Global Assessment of Disease Activity (MDGA) and Extramuscular Global Assessment of the Myositis Disease Activity Assessment Tool (MDAAT) of 0, along with normal creatine kinase (CK) values for at least 12 weeks, evaluated at weeks 24 and 52. Additionally, the percentage of participants achieving remission, defined as a clinically inactive disease for at least 24 weeks, will be determined during the study.