Evaluation of Imlifidase for Acute Inflammation in AQP4-IgG Associated Neuromyelitis Optica Spectrum Disorder

The primary objective of this study is to evaluate the **depletion** of circulating pathogenic anti-AQP4 IgG antibodies in participants with severe optic neuritis and/or myelitis associated with **neuromyelitis optica spectrum disorder** (NMOSD). The effectiveness of **imlifidase** treatment will be assessed by measuring the proportion of participants whose antibody levels fall below the detection limit within 6 hours post-treatment, using a cell-based assay. This objective is clinically relevant as it aims to address acute inflammation in NMOSD, potentially improving patient outcomes by reducing antibody-mediated damage.

The clinical trial involves participants diagnosed with **neuromyelitis optica spectrum disorder** (NMOSD), also known as Devic disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a positive anti-AQP4 IgG serum test, either at presentation or in their medical history, and must present with severe optic neuritis and/or myelitis. The trial does not include a vulnerable population. Participants are expected to comply with specific lifestyle considerations, such as the use of effective contraceptive methods for women of child-bearing potential and double-barrier contraception for men, if not abstinent, for a specified period post-treatment. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **imlifidase** in treating acute inflammation in patients with **neuromyelitis optica spectrum disorder** (NMOSD). This is a Phase 4, randomized, double-blind, controlled trial. The primary objective is to analyze the proportion of participants with a depletion of circulating pathogenic anti-AQP4 IgG antibodies below detection limits within six hours after treatment. The trial is expected to commence recruitment on December 1, 2023, and conclude by December 1, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and serological status. Following successful screening, participants will be randomized to receive the investigational product, **Idefirix 11 mg powder for concentrate for solution for infusion**, administered intravenously. The trial includes follow-up visits to monitor the depletion of antibodies and assess any adverse events. The end-of-study visit will evaluate the overall treatment efficacy and safety.

The expected duration of participant involvement is approximately one month, with the maximum treatment period being one day. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of significant adverse events. Participants are required to adhere to contraceptive measures if applicable, and those with certain viral infections are excluded from participation. The trial aims to provide valuable insights into the potential benefits of **imlifidase** in managing NMOSD exacerbations.

The clinical trial involves the administration of the experimental medication **Idefirix**, which contains the active substance **imlifidase**. Idefirix is formulated as a **powder for concentrate for solution for infusion**. The pharmaceutical form is a **solution for infusion**, and it is administered via the **intravenous** route. The dosage is calculated based on body weight, with a maximum daily dose of 0.25 mg/kg. The total dose also does not exceed 0.25 mg/kg, and the treatment period is limited to a single day. The active substance, imlifidase, is a protein of other origin, and the product is manufactured by Hansa Biopharma AB. The medication is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of Idefirix to evaluate its efficacy in depleting circulating pathogenic anti-AQP4 IgG antibodies in participants with severe optic neuritis and/or myelitis associated with neuromyelitis optica spectrum disorder. Compliance with the dosing schedule is monitored to ensure adherence to the protocol, and the primary objective is to measure the antibody depletion within six hours post-treatment using a cell-based assay.

Efficacy in the clinical trial titled "Imlifidase treatment for acute inflammation in AQP4-IgG associated neuromyelitis optica spectrum disorder (DEFEAT NMOSD)" will be assessed by evaluating the primary endpoint. The primary endpoint is defined as the proportion of participants achieving a depletion of circulating pathogenic anti-AQP4 IgG antibodies below detection limits. This will be measured using a state-of-the-art cell-based assay within a timeframe of 6 hours post-treatment with **imlifidase**. The trial aims to determine the effectiveness of imlifidase in reducing these antibodies in participants presenting with severe optic neuritis and/or myelitis. The assessment will focus on the immediate impact of the treatment, providing insights into the potential of imlifidase to address acute exacerbations in neuromyelitis optica spectrum disorder.