An Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Donidalorsen in Pediatric Patients with Hereditary Angioedema

The primary objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of donidalorsen in pediatric patients diagnosed with hereditary angioedema. Secondary objectives include:

• Assessment of efficacy regarding donidalorsen administration.
• Evaluation of plasma prekallikrein levels to determine pharmacodynamics.
• Measurement of the impact of treatment on quality of life.

This clinical trial involves 12 participants diagnosed with hereditary angioedema. The study population consists of pediatric patients, including both males and females, who are categorized as a vulnerable population. Eligible subjects must be between 2 and 11 years of age at the time of informed consent and must have a body mass of at least 9 kg. Inclusion requires a documented diagnosis of HAE-1 or HAE-2, established through a clinical history consistent with the condition and confirmed via diagnostic testing.

This Phase 3, open-label study is designed to evaluate the safety, tolerability, and pharmacokinetics of donidalorsen in pediatric patients diagnosed with hereditary angioedema. Eligible participants must be between 2 and less than 12 years of age, weigh at least 9 kg, and have a documented diagnosis of HAE-1 or HAE-2. The investigational product is administered via subcutaneous injection. Primary endpoints include the incidence and severity of treatment-emergent adverse events and plasma concentrations of the drug. Secondary objectives involve assessing the monthly frequency of investigator-confirmed attacks, the percentage of attack-free participants, and changes in plasma prekallikrein levels and pediatric quality of life scores over a 12-month period. The study involves a sequence of clinical visits to monitor clinical response and safety throughout the 12-month observation period.

The investigational medicinal product is donidalorsen, an orphan drug administered as a subcutaneous injection. This substance is being evaluated for the treatment of hereditary angioedema.

The efficacy of donidalorsen in patients with hereditary angioedema will be assessed through several secondary endpoints over a 12-month period. These include the time-normalized number of investigator-confirmed attacks per month and the percentage of participants remaining attack-free. Additionally, the time-normalized frequency of moderate or severe attacks per month will be monitored. Clinical response is defined as a specific percentage reduction from baseline in the investigator-confirmed attack rate, specifically reductions of ≥ 50%, ≥ 70%, or ≥ 90%. The frequency of attacks requiring rescue treatment will also be evaluated.

Biochemical and patient-reported outcomes are utilized to further measure efficacy. These consist of changes in plasma prekallikrein levels and variations in Pediatric Quality of Life scores. All measurements for these parameters are planned for collection over a 12-month duration.