Evaluation of Safety, Tolerability, and Efficacy of Peginterferon Beta-1a in Pediatric Patients with Relapsing-Remitting Multiple Sclerosis

The primary objective of this study is to evaluate the **safety**, tolerability, and descriptive efficacy of BIIB017, also known as **peginterferon beta-1a**, in pediatric participants with **relapsing-remitting multiple sclerosis (RRMS)**. This evaluation is crucial for understanding the potential benefits and risks of BIIB017 in a younger population, which can inform treatment decisions and improve patient outcomes. Additionally, the study aims to assess the pharmacokinetics of BIIB017 in this demographic during Part 1. In Part 2, the study will focus on the long-term safety of BIIB017 and further describe safety and long-term multiple sclerosis outcomes after treatment in participants who completed the study treatment at Week 96 in Part 1.

The clinical trial involves a total of **73 participants** diagnosed with **Relapsing Remitting Multiple Sclerosis (RRMS)**. The study population includes both male and female pediatric subjects, with an age range that corresponds to the pediatric category. Participants were selected based on specific criteria, including a confirmed diagnosis of RRMS and an Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5. The trial also considers individuals who have experienced at least one relapse in the 12 months prior to randomization or have evidence of asymptomatic disease activity on brain MRI. The study population is characterized as a vulnerable group due to the pediatric nature of the participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as an open-label, randomized, multicenter, active-controlled, parallel-group study to evaluate the safety, tolerability, and efficacy of **peginterferon beta-1a** in pediatric subjects aged 10 to less than 18 years for the treatment of **relapsing-remitting multiple sclerosis** (RRMS). The trial is divided into two parts, with Part 1 focusing on the evaluation of safety, tolerability, and descriptive efficacy, as well as the pharmacokinetics of the investigational product. Part 2 aims to assess the long-term safety and outcomes of the treatment in participants who completed the study treatment at Week 96 in Part 1. The trial is expected to conclude by November 15, 2027, with recruitment having started on October 31, 2019.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of RRMS, an Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5, and a history of relapses or evidence of asymptomatic disease activity. The primary endpoint for Part 1 is the annualized relapse rate (ARR) at Week 48, while Part 2 focuses on the percentage of participants with adverse events and serious adverse events from Week 96 to Week 196. Secondary endpoints include various measures of disease activity and progression, such as MRI findings, relapse rates, and changes in cognitive and quality of life assessments.

The expected length of participant involvement is up to 196 weeks, with conditions for early termination including the occurrence of adverse events leading to study treatment discontinuation. Study visits are scheduled at regular intervals to monitor safety, efficacy, and pharmacokinetic parameters, with assessments including MRI scans, clinical laboratory evaluations, and various health and quality of life questionnaires. The investigational product is administered via subcutaneous injection, with the study utilizing both test and comparator products to evaluate outcomes. Participants who complete Part 1 of the study are eligible to continue into Part 2, which further investigates long-term safety and efficacy outcomes.

The clinical trial involves the administration of several treatments, including **AVONEX** and **Plegridy**, both of which are solutions for injection. **AVONEX** is provided in two forms: a 30 micrograms/0.5 ml solution for injection in a pre-filled pen and a 30 micrograms/0.5 ml solution for injection. The active substance in **AVONEX** is **interferon beta-1a**, a protein of biological/biotechnological origin. The pre-filled pen formulation is administered via **intramuscular use**, while the standard solution is administered via **subcutaneous use**. Both formulations are identical to the EU marketed product but are packaged specifically for clinical use. The maximum treatment period for these formulations is one week, with no specified maximum daily or total dose amount.

**Plegridy** is another treatment used in the trial, available in two formulations: a 63 micrograms + 94 micrograms solution for injection in a pre-filled pen and a 125 micrograms solution for injection in a pre-filled pen. The active substance in **Plegridy** is **peginterferon beta-1a**, also a protein of biological/biotechnological origin. Both formulations are administered via **subcutaneous use**. Similar to **AVONEX**, these formulations are identical to the EU marketed product but are packaged for clinical use. The maximum treatment period for **Plegridy** is one week, with no specified maximum daily or total dose amount.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the treatment regimen. The trial aims to evaluate the safety, tolerability, and efficacy of these treatments in pediatric subjects with **relapsing-remitting multiple sclerosis**. The study is designed to assess both short-term and long-term outcomes following treatment with these medications.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint for Part 1 of the study is the annualized relapse rate (ARR) at Week 48. In Part 2, the primary endpoint focuses on the percentage of participants experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study treatment discontinuation from Week 96 to Week 196.

Secondary endpoints in Part 1 include the ARR at Week 48, the percentage of participants free of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24, 48, and 96, and the percentage of participants free of new MRI activity in the brain at the same time points. Additional secondary endpoints involve the number of new or newly enlarging T2 hyperintense lesions, the number of Gd-enhancing lesions on brain MRI scans, and the time to first relapse up to Week 96. Other measures include changes from baseline in cognition, as measured by the Symbol Digit Modality Test (SDMT), and changes in the Expanded Disability Status Scale (EDSS) score, quality of life as measured by the Pediatric Quality of Life Inventory (PedsQL), and various pharmacokinetic parameters of **BIIB017**.

In Part 2, secondary endpoints include the ARR at Weeks 144 and 192, changes from baseline in EDSS score, height, weight, and Tanner score at specified intervals, and the number of participants with binding and neutralizing antibodies to **interferon beta-1a**. Additional assessments involve changes in vital signs, such as blood pressure, pulse rate, body temperature, and respiratory rate, as well as changes in depression as assessed by the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and clinical laboratory values over time.