Long-Term Evaluation of Safety and Efficacy of Verekitug (UPB-101), a Human IgG1 Kappa Monoclonal Antibody Against CRLF2, in Adults with Severe Asthma

The primary objective of this study is to evaluate the **safety** and **tolerability** of long-term treatment with **Verekitug (UPB-101)** in adults with severe asthma. This is clinically relevant as it aims to ensure that the therapeutic intervention does not pose undue risk to patients and can be sustained over an extended period, which is crucial for managing a chronic condition like severe asthma.

Secondary objectives include assessing the impact of Verekitug on asthma attacks, breathing ability, airway inflammation, and overall asthma management. Additionally, the study aims to understand how the body processes Verekitug and to monitor for any immune response to the treatment. These objectives are important for comprehensively evaluating the drug's efficacy and pharmacokinetics, as well as its potential immunogenicity, which are critical factors in determining the overall benefit-risk profile of the treatment for severe asthma patients.

The clinical trial involves a total of **312 participants** diagnosed with **severe asthma**. The study population includes both male and female adults, with an age range that encompasses individuals from young adults to older adults. Participants were selected based on their completion of the VALIANT study per protocol, ensuring they did not meet discontinuation criteria and attended the VALIANT end-of-study visit. The trial population includes a vulnerable group, indicating special considerations in the study design. Participants are required to adhere to local regulations regarding contraceptive use, reflecting lifestyle considerations pertinent to the study. The trial aims to evaluate the long-term safety and tolerability of verekitug in this specific population.

The clinical trial is designed to evaluate the long-term safety and efficacy of **Verekitug (UPB-101)** in adult participants with **severe asthma** who have completed the VALIANT trial. This study is a Phase 4, randomized, double-blind, controlled trial. Participants will be randomly assigned to receive either the active treatment, **Verekitug (UPB-101)**, a **human IgG1 kappa monoclonal antibody against CRLF2**, or a matching placebo solution for subcutaneous injection. The trial is expected to last approximately 60 weeks, with participant involvement beginning from the first visit and continuing until the end-of-study visit.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits throughout the trial duration. The inclusion criteria require participants to have completed the VALIANT study per protocol, signed informed consent, and adhere to local contraceptive regulations. The primary endpoint is to assess the safety of **Verekitug** by monitoring side effects, conducting physical examinations, and performing clinical laboratory assessments, vital sign measurements, and ECGs. Secondary endpoints include recording the number of severe asthma flare-ups requiring steroid treatment, changes in lung function, airway inflammation, and asthma management, as well as measuring the concentration of **Verekitug** in the blood and checking for antibodies against it.

Participants are expected to be involved in the study for the entire 60-week period unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. The trial is scheduled to start recruitment in October 2025 and is estimated to conclude by August 2027. The study aims to provide comprehensive data on the long-term use of **Verekitug** in managing severe asthma, contributing to the understanding of its safety and efficacy profile.

The clinical trial involves the administration of **Verekitug (UPB-101)**, an experimental medication formulated as a **solution for injection**. This investigational product is a **human IgG1 kappa monoclonal antibody against CRLF2**, developed by UPSTREAM BIO, INC. The pharmaceutical form is specifically designed for **subcutaneous use**. The dosing regimen for Verekitug (UPB-101) is determined by the study protocol, with a maximum treatment period of 60 days. The trial does not specify a maximum daily or total dose amount, indicating that dosing may be adjusted based on individual participant response and tolerability. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, the study includes a **placebo** control, referred to as **Veritikug (UPB-101) matching solution for subcutaneous injection with no active treatment**. This placebo is designed to match the experimental medication in appearance and administration route but contains no active therapeutic ingredients. The use of a placebo allows for the assessment of the efficacy and safety of Verekitug (UPB-101) by providing a baseline for comparison. Participants receiving the placebo will follow the same administration schedule as those receiving the active treatment, ensuring consistency across the study groups.

The efficacy of Verekitug (UPB-101) in the clinical trial will be assessed through several secondary endpoints. These include the number of severe asthma flare-ups or attacks requiring treatment with steroids over a 60-week period. Additionally, changes from the start of the Long-Term Extension (LTE) study up to Week 60 will be recorded for the following parameters: the volume of air a participant can forcefully exhale in one second, the level of nitric oxide in exhaled air as an indicator of airway inflammation, and the management of asthma symptoms as evaluated by a scored questionnaire.

Furthermore, the pharmacokinetics of Verekitug will be evaluated by measuring its concentration in the blood at each visit. The presence of antibodies against Verekitug will also be monitored throughout the LTE study to assess any immune response. These assessments will provide comprehensive data on the efficacy of Verekitug in managing severe asthma in adult participants who have completed the VALIANT trial.