Evaluation of Efficacy, Safety, and Pharmacokinetics of Human Normal Immunoglobulin (IgPro20) in Adults with Dermatomyositis: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of IgPro20, a subcutaneous immunoglobulin, in comparison to placebo in adult subjects with **dermatomyositis**. This is assessed by the responder status based on the Total Improvement Score (TIS) at Weeks 17, 21, and 25. The clinical relevance of this objective lies in determining the potential of IgPro20 to improve clinical outcomes in patients with dermatomyositis, a condition characterized by muscle weakness and skin rash, which can significantly impact quality of life.

The secondary objectives of the study include:

• Assessing the efficacy of IgPro20 with additional clinical outcome measures compared to placebo.
• Evaluating the safety of IgPro20 in comparison to placebo.
• Determining the safety and efficacy of IgPro20 at Week 53.
• Assessing the safety of IgPro20 after Week 53 until the end of study participation.

The clinical trial involves a total of **60 participants** diagnosed with **dermatomyositis**, a type of idiopathic inflammatory myopathy. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria, which require confirmation of dermatomyositis rash or manifestation, active disease presence, and a defined level of disease severity. The trial does not specify particular lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, indicating that special ethical considerations are in place to protect these participants. The trial aims to evaluate the efficacy of IgPro20 SC doses compared to a placebo, with assessments conducted at specific intervals to determine responder status based on the Total Improvement Score (TIS).

The clinical trial is designed to evaluate the **efficacy**, safety, and pharmacokinetics of IgPro20, a subcutaneous immunoglobulin, in adults diagnosed with **dermatomyositis**. This study is structured as a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thus minimizing bias. The trial is expected to span approximately eight years, with the estimated end date set for November 30, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age and disease severity. Following successful screening, participants will be randomized to receive either IgPro20 or a placebo. The primary endpoint is the responder rate, defined by a Total Improvement Score (TIS) of at least 20 points at Week 25, without the use of rescue corticosteroid treatment. Secondary endpoints include various measures of disease activity and treatment response, assessed up to Week 53.

Study visits are scheduled at regular intervals, including key assessments at Weeks 17, 21, and 25, to monitor the participants' progress and response to treatment. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted. Participants are expected to be involved in the study for a maximum of 53 weeks, with conditions for early termination including significant adverse events or withdrawal of consent.

The trial aims to provide comprehensive data on the potential benefits of IgPro20 in managing dermatomyositis, with a focus on improving patient outcomes through rigorous scientific evaluation. The study's design and methodology adhere to high standards of clinical research, ensuring the reliability and validity of the findings.

The clinical trial involves the administration of **Hizentra 200 mg/ml solution for subcutaneous injection**, which is the experimental medication being evaluated. This pharmaceutical product is a **solution for subcutaneous injection** containing **human normal immunoglobulin** as the active substance. The medication is administered subcutaneously, with a maximum daily dose of 500 mg/kg and a total maximum dose of 1,461,000 mg/kg over a treatment period of up to 84 days. The product is manufactured by CSL Behring GmbH and is authorized for use in the European Union under the marketing authorization number EU/1/11/687/014. The primary objective of the study is to assess the efficacy of IgPro20 SC doses in comparison to placebo in adult subjects with dermatomyositis, as measured by responder status based on the Total Improvement Score assessments at Weeks 17, 21, and 25.

In addition to the experimental treatment, the study utilizes a **placebo** control, which is a **2% human albumin** solution. This placebo is used to provide a baseline for comparison against the active treatment. The placebo is administered in a manner consistent with the experimental medication to ensure blinding and maintain the integrity of the study design. The use of a placebo allows for the assessment of the true efficacy and safety profile of the experimental treatment by providing a control group for comparison.

The efficacy of IgPro20 (Hizentra®) in adults with **Dermatomyositis (DM)** will be assessed through a series of predefined endpoints. The primary endpoint is the responder rate, defined as subjects achieving a Total Improvement Score (TIS) of at least 20 points at Week 25 and at one of the previous scheduled visits (Week 17 or Week 21), without the use of rescue corticosteroid treatment. The TIS is a composite measure incorporating six weighted IMACS core set measures (CSMs).

Secondary endpoints include the mean TIS up to Week 25, point estimates and 95% confidence intervals (CI) for the mean difference in TIS between IgPro20 and placebo, and mean changes from baseline in Manual Muscle Testing (MMT-8) and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score. Additional secondary endpoints involve the percentage of subjects able to reduce oral corticosteroid dose by at least 25%, and the time to first achieving TIS thresholds of 20, 40, and 60 points, among others.

Efficacy assessments will be conducted at multiple timepoints, including Weeks 5, 17, 21, 25, and up to Week 53. The analysis will include point estimates and 95% CIs for differences between treatment groups, as well as the percentage of subjects achieving specific improvement criteria. These assessments will provide a comprehensive evaluation of the treatment's impact on disease activity and patient outcomes over the course of the study.