C0251006 - A PHASE 3, MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-06823859 IN PARTICIPANTS WITH ACTIVE IDIOPATHIC INFLAMMATORY MYOPATHIES (INCLUDING PARTICIPANTS WITH ACTIVE DERMATOMYOSITIS OR POLYMYOSITIS)

The primary objective of this study is to evaluate the **efficacy** of PF-06823859 compared with placebo in reducing muscle symptoms in adult participants with active dermatomyositis (DM) and active polymyositis (PM). This is clinically relevant as it aims to address the muscle-related manifestations of these idiopathic inflammatory myopathies, which can significantly impact patient quality of life and physical function.

Secondary objectives include evaluating the efficacy of PF-06823859 compared with placebo in reducing skin signs and symptoms in Cohort 1, as well as muscle signs and symptoms in both Cohorts 1 and 2. Additionally, the study aims to assess the impact on patient health status in adult participants with active DM and PM. These objectives are important for understanding the broader therapeutic potential of PF-06823859 in managing both cutaneous and systemic manifestations of these conditions.

The clinical trial involves a total of **193 participants** diagnosed with **Active Idiopathic Inflammatory Myopathies**, including **Dermatomyositis** and **Polymyositis**. The study population comprises adults aged 18 years and older, with both male and female participants included. Participants were selected based on specific criteria, including a confirmed diagnosis of definite or probable idiopathic inflammatory myopathy as per ACR/EULAR classification criteria, and a disease activity/severity that meets predefined thresholds. All participants are required to be on a stable dose of standard-of-care background medications, which may include oral corticosteroids, immunosuppressants, or a combination of both. The trial does not exclude vulnerable populations, indicating a broad inclusion of individuals who meet the health criteria. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of PF-06823859 in participants with active idiopathic inflammatory myopathies, including dermatomyositis and polymyositis. The trial aims to assess the reduction in muscle symptoms in adult participants. The study will span approximately 52 weeks, with an estimated recruitment start date of November 15, 2023, and an estimated end date of November 27, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, disease classification, and current treatment regimen. Following successful screening, participants will be randomized to receive either the investigational product, PF-06823859, or a placebo. The investigational product is administered as a **solution for injection** via **intravenous administration**. The trial includes multiple follow-up visits to monitor the participants' response to treatment and any adverse events. These visits will assess primary and secondary endpoints, including changes in muscle strength and overall disease activity.

The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted to evaluate the long-term efficacy and safety of the treatment. Participant involvement is expected to last the entire duration of the trial unless early termination is warranted. Conditions for early termination may include significant adverse events, withdrawal of consent, or non-compliance with the study protocol.

The clinical trial involves the administration of **Dazukibart**, a solution for injection, which is a humanised IgG1K monoclonal antibody against interferon beta. This experimental medication is administered via **intravenous administration**. The maximum daily dose is 600 mg, with a total maximum dose of 7800 mg over a treatment period of 52 weeks. Participant compliance is monitored to ensure adherence to the dosing schedule.

**PF-06823859** is another experimental medication used in the trial, also formulated as a solution for injection. It shares the same active substance as Dazukibart and is administered intravenously. The dosing regimen mirrors that of Dazukibart, with a maximum daily dose of 600 mg and a total maximum dose of 7800 mg over 52 weeks.

The study includes a **placebo** for PF-06823859, designed to match the solution for injection in appearance and administration route, ensuring the double-blind nature of the trial. The placebo is administered intravenously, with dosing schedules aligned with the active treatment groups.

**Methotrexate** is utilized as a non-experimental treatment in the study, available in both tablet and solution for injection forms. The oral administration of methotrexate tablets is limited to a maximum daily dose of 3.5 mg, while the injectable form is administered intravenously with the same dosing limits. The treatment period extends up to 52 weeks.

**Azathioprine** is included as an immunosuppressive agent, administered orally in the form of an oral suspension. The maximum daily dose is 150 mg, with a total maximum dose of 150 mg over the 52-week treatment period.

**Methylprednisolone** is provided in both tablet and solution for injection/infusion forms. The oral form is administered with a maximum daily dose of 48 mg, while the injectable form is administered intramuscularly with the same dosing limits. The treatment duration is 52 weeks.

**Dexamethasone** is administered as a solution for injection via intravenous injection, with a maximum daily dose of 9 mg and a total maximum dose of 9 mg over 52 weeks.

**Betamethasone** is available in both tablet and solution for injection forms. The oral administration is limited to a maximum daily dose of 7.2 mg, while the injectable form is administered intravenously with the same dosing limits. The treatment period is 52 weeks.

**Prednisolone** and **Prednisone** are both administered orally in tablet form, with a maximum daily dose of 60 mg and a total maximum dose of 60 mg over the 52-week treatment period.

**Deflazacort** is administered orally in tablet form, with a maximum daily dose of 72 mg and a total maximum dose of 72 mg over 52 weeks.

**Triamcinolone Acetonide** is administered as a suspension for injection via intradermal route, with a maximum daily dose of 48 mg and a total maximum dose of 48 mg over 52 weeks.

**Budesonide** is provided as a prolonged-release capsule, administered orally with a maximum daily dose of 18 mg and a total maximum dose of 18 mg over 52 weeks.

**Leflunomide** is administered orally in tablet form, with a maximum daily dose of 20 mg and a total maximum dose of 20 mg over the 52-week treatment period.

**Hydroxychloroquine** and **Proguanil Hydrochloride** are included as antiprotozoal and antimalarial agents, administered orally. Hydroxychloroquine has a maximum daily dose of 400 mg over a 32-week period, while Proguanil Hydrochloride has a maximum daily dose of 250 mg over the same period.

**Mycophenolate Mofetil** is administered orally in capsule form, with a maximum daily dose of 3000 mg and a total maximum dose of 3000 mg over 52 weeks.

**Hydrocortisone** is administered orally in tablet form, with a maximum daily dose of 240 mg and a total maximum dose of 240 mg over the 52-week treatment period.

The efficacy of PF-06823859 in the treatment of active **Idiopathic Inflammatory Myopathies** (IIM), including active dermatomyositis (DM) and polymyositis (PM), will be assessed through a series of primary and secondary endpoints. The primary endpoint for efficacy evaluation is the moderate improvement in the Total Improvement Score (TIS) at Week 24 for both DM and PM cohorts. Secondary endpoints include changes from baseline in the Manual Muscle Testing (MMT-8) score at Week 24, normalized area under the curve (AUC) of corticosteroid dose over 52 weeks, moderate improvement in TIS at Week 52, and changes from baseline in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores at Week 24.

These efficacy parameters will be measured and collected at specified timepoints, including Week 24 and Week 52, using validated scales and patient-reported outcomes. The analysis will focus on comparing the changes from baseline in these scores to evaluate the treatment's impact on muscle symptoms and overall disease activity. The trial is designed as a phase 3, multicenter, double-blind, randomized, placebo-controlled study, ensuring rigorous assessment of the treatment's efficacy in the target population.