Long-Term Safety and Tolerability Assessment of Dexpramipexole in Severe Eosinophilic Asthma: An Open-Label Phase III Extension Study

The primary objective of this study is to assess the long-term **safety** of Dexpramipexole 150 mg BID in participants with severe eosinophilic asthma who have completed either of the Phase III studies EXHALE-2 or EXHALE-3. Evaluating the safety profile of Dexpramipexole is clinically relevant as it ensures the therapeutic agent's risk-benefit ratio is favorable for long-term use in managing severe eosinophilic asthma, a condition characterized by high levels of eosinophils and associated with significant morbidity.

Secondary objectives include:

• Assessing the long-term efficacy of Dexpramipexole in participants with eosinophilic asthma who completed either of the Phase III studies EXHALE-2 or EXHALE-3. This evaluation is crucial for understanding the sustained therapeutic benefits of the drug.
• Evaluating the effect of Dexpramipexole on blood eosinophils, which is important for determining the drug's impact on a key biomarker associated with the pathophysiology of eosinophilic asthma.

The clinical trial involves a total of **1336 participants** who have been diagnosed with **severe eosinophilic asthma**. The study population includes both male and female subjects, encompassing a diverse age range. Participants were selected based on their completion of the double-blind study intervention treatment period during either of the Phase III studies EXHALE-2 or EXHALE-3. The trial includes individuals from a vulnerable population, indicating a careful consideration of ethical standards in participant selection. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data. The trial's primary focus is to assess the long-term safety of dexpramipexole 150 mg BID, ensuring that participants meet specific health criteria, including a negative urine pregnancy test for women of childbearing potential. The study's design reflects a comprehensive approach to understanding the safety profile of the medication in a real-world setting.

The clinical trial is designed as an **open-label** Phase III extension study to evaluate the long-term safety and tolerability of **dexpramipexole** in participants with severe eosinophilic asthma. The trial will involve participants who have completed the double-blind study intervention treatment period during either of the Phase III studies EXHALE-2 or EXHALE-3. The primary objective is to assess the long-term safety of dexpramipexole 150 mg administered orally twice daily (BID). The trial will monitor treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs, and 12-lead ECGs as primary endpoints. Secondary endpoints include the annualized rate of severe asthma exacerbations over 52 weeks, changes in the Asthma Control Questionnaire-6 (ACQ-6) scores, and absolute eosinophil counts at specified intervals.

The trial is expected to last for a maximum of 52 weeks, with participant involvement beginning from the baseline visit and continuing through to the end-of-study visit. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits at Weeks 16, 32, and 52 to assess the secondary endpoints. The end-of-study visit will conclude the participant's involvement in the trial. Participants are required to adhere to specific inclusion criteria, such as having completed the prior Phase III studies and providing informed consent. Women of childbearing potential must use effective birth control methods throughout the study duration.

Participants may be subject to early termination from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial is not categorized as a low-intervention study and is conducted in accordance with regulatory guidelines to ensure the safety and well-being of all participants. The estimated recruitment start date is September 9, 2024, with an anticipated end date of February 20, 2027. The study is sponsored by Areteia Therapeutics, and the investigational product is administered in the form of a film-coated tablet.

The clinical trial involves the administration of **Dexpramipexole (KNS-760704)**, a chemical compound formulated as a **film-coated tablet**. The active substance in this medication is **dexpramipexole dihydrochloride monohydrate**. The pharmaceutical form is designed for **oral** administration. Participants in the study will receive a dosage of 150 mg, administered twice daily (BID). The maximum daily dose is 150 mg, and the treatment period extends up to 52 weeks. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to assess the long-term safety and tolerability of dexpramipexole in individuals with severe eosinophilic asthma who have completed previous Phase III studies, EXHALE-2 or EXHALE-3.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of dexpramipexole. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The study is conducted under the sponsorship of Areteia Therapeutics, and the medication is identified by the sponsor product code "Dexpramipexole". The trial does not involve any additional devices or interventions beyond the administration of the investigational product.

Efficacy in the clinical trial will be assessed using several key parameters. The primary endpoint involves the assessment of treatment emergent adverse events (TEAEs), clinical laboratory parameters, vital signs, and 12-lead ECGs. Secondary endpoints include the annualized rate of severe asthma exacerbations over 52 weeks, changes in the Asthma Control Questionnaire-6 (ACQ-6) scores from baseline at Weeks 16, 32, and 52, and changes in absolute eosinophil counts (AEC) from baseline at the same timepoints.

The efficacy parameters will be measured and collected at specified intervals throughout the trial. The ACQ-6, a validated scale, will be used to evaluate changes in asthma control, while laboratory tests will be conducted to determine changes in eosinophil counts. These assessments will occur at Weeks 16, 32, and 52, providing a comprehensive overview of the treatment's impact over the course of the study.