Efficacy and Safety of Subcutaneous Anifrolumab Versus Placebo in Adult Idiopathic Inflammatory Myopathies: A Phase III, Double-Blind, Multicenter Study

The primary objective of this study is to demonstrate the superiority of **anifrolumab** compared to placebo in achieving moderate improvement in disease activity at Week 52 in adult participants with idiopathic inflammatory myopathies, specifically polymyositis and dermatomyositis. This objective is clinically relevant as it aims to establish anifrolumab as a more effective treatment option, potentially leading to better management of these chronic conditions.

Secondary objectives include:

• Demonstrating the superiority of anifrolumab over placebo in muscle improvement at Week 52.
• Assessing the reduction in oral corticosteroid dose at Week 52.
• Evaluating moderate improvement in disease activity in participants with polymyositis (PM) and dermatomyositis (DM) at Week 52.
• Improving skin activity at Week 8.
• Assessing the efficacy of anifrolumab compared with placebo on muscle improvement and oral corticosteroid dose reduction in both PM and DM participants at Week 52.

The clinical trial involves a total of **120 participants** diagnosed with **polymyositis** or **dermatomyositis** as per the 2017 EULAR/ACR classification criteria. The study population comprises both male and female subjects, aged between **18 and 75 years**, with a body weight ranging from **40 kg to 100 kg**. Participants were selected based on their moderate or severe disease activity, as measured by core set assessments, and are currently receiving stable doses of oral prednisone or other treatments for polymyositis or dermatomyositis. The trial includes individuals without a history of active tuberculosis or severe COVID-19. Both genders are required to adhere to contraception guidelines. The study population is considered vulnerable, and the selection process ensures a representative sample of the affected demographic. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy and safety of **anifrolumab** administered as a subcutaneous injection in adult participants with **idiopathic inflammatory myopathies**, specifically polymyositis and dermatomyositis. The trial is structured as a parallel-group, two-arm, Phase III study, comparing anifrolumab added to standard care against a placebo added to standard care. The primary objective is to demonstrate the superiority of anifrolumab over placebo in achieving moderate improvement in disease activity at Week 52. The trial is expected to commence recruitment on September 3, 2024, and conclude by June 15, 2028, with a maximum treatment period of 104 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (18-75 years), body weight (40-100 kg), and a confirmed diagnosis of polymyositis or dermatomyositis according to the 2017 EULAR/ACR classification criteria. Eligible participants must exhibit moderate or severe disease activity and be on a stable dose of oral prednisone or other relevant treatments. Exclusion criteria include a history of active tuberculosis or severe COVID-19. Following the screening, participants will be randomized to receive either anifrolumab or placebo, both administered via subcutaneous injection using an accessorized pre-filled syringe (APFS).

Study visits will be scheduled at regular intervals to monitor disease activity, treatment adherence, and safety. The primary endpoint is the proportion of participants achieving at least moderate improvement in disease activity without confirmed deterioration at two consecutive visits. Secondary endpoints include changes in MMT-8 (CSM) scores, corticosteroid dose reduction, and CDASI-activity changes for dermatomyositis participants. The end-of-study visit will assess the overall treatment efficacy and safety profile. Participant involvement is expected to last up to 104 weeks, with conditions for early termination including significant adverse events or non-compliance with study protocols.

The clinical trial involves the administration of **Anifrolumab**, a **solution for injection** designed for **subcutaneous use**. Anifrolumab is an investigational medication developed by AstraZeneca AB, identified by the sponsor product code MEDI-546. The active substance, anifrolumab, is a protein of other origin. The maximum daily dose is 17.14 mg/ml, and the treatment period extends up to 104 weeks. The administration is facilitated by an accessorized pre-filled syringe (APFS), a single-use, disposable system that ensures the delivery of the labeled dose to the subcutaneous space in one injection. The APFS also includes a safety mechanism to minimize accidental needle sticks during disposal.

The trial also includes a **placebo** group, where participants receive Anifrolumab Placebo, which is administered in the same manner as the active treatment. The placebo is used to compare the efficacy and safety of Anifrolumab when added to the standard of care in adult participants with idiopathic inflammatory myopathies, specifically polymyositis and dermatomyositis. The placebo is designed to mimic the pharmaceutical form and administration route of the active treatment to maintain the double-blind nature of the study.

Both Anifrolumab and the placebo are administered in conjunction with standard-of-care therapy, which is not specified in the trial data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The primary objective of the trial is to demonstrate the superiority of Anifrolumab over the placebo in achieving moderate improvement in disease activity at Week 52.

The efficacy of Anifrolumab in the treatment of **Idiopathic Inflammatory Myopathies** (Polymyositis and Dermatomyositis) will be assessed in a multicenter, parallel-group, double-blind, Phase III clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants who achieve at least moderate improvement in disease activity, defined as a Total Improvement Score (TIS) of 40 or greater, without meeting the criteria for "confirmed deterioration" at two consecutive visits by Week 52.

Secondary endpoints include changes in the Manual Muscle Test (MMT-8) from baseline at Week 52, the proportion of participants achieving an oral corticosteroid dose of 7.5 mg/day or less at Week 52, and specific assessments for Polymyositis (PM) and Dermatomyositis (DM) participants. For DM participants, the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity change from baseline will be evaluated at Week 8. These endpoints will be measured using validated scales and patient-reported outcomes at specified timepoints throughout the study.

The trial will utilize a subcutaneous injection of Anifrolumab, administered using an accessorized pre-filled syringe (APFS), which is designed to ensure accurate dosing and minimize accidental needle sticks. The study aims to demonstrate the superiority of Anifrolumab over placebo when added to the standard of care, with efficacy assessments conducted at various intervals up to the end of the treatment period at Week 52.