Comparison of Efficacy and Safety of BP11 and EU-Approved Omalizumab in Chronic Spontaneous Urticaria Resistant to H1 Antihistamines

The primary objective of this study is to demonstrate **therapeutic equivalence** between BP11 and Xolair in patients with **chronic spontaneous urticaria** (CSU) who exhibit an inadequate response to H1 antihistamine (H1AH) treatment. Establishing therapeutic equivalence is clinically significant as it may provide an alternative treatment option for patients who are resistant to current therapies, potentially improving patient outcomes and expanding available therapeutic choices.

Secondary objectives include:

• Assessing and comparing other efficacy parameters between BP11 and Xolair over time.
• Evaluating and comparing safety and tolerability between BP11 and Xolair throughout the study period.
• Assessing and comparing **immunogenicity** between BP11 and Xolair during the study.
• Evaluating and comparing the **pharmacokinetics** (PK) between BP11 and Xolair over the study.
• Assessing and comparing the **pharmacodynamics** (PD) between BP11 and Xolair.

These secondary objectives aim to provide a comprehensive evaluation of the comparative performance of BP11 and Xolair, which is crucial for understanding the overall therapeutic profile and ensuring patient safety and efficacy in the management of chronic spontaneous urticaria.

The clinical trial involves a total of **126 participants** diagnosed with **Chronic Urticaria**, specifically focusing on individuals with chronic spontaneous urticaria (CSU) who have shown an inadequate response to H1 antihistamine treatment. The study population comprises both male and female subjects, aged between **18 to 75 years**. Participants were selected based on their willingness and ability to provide informed consent, as well as their capability to maintain consistent e-diary entries. The trial includes individuals who have had a diagnosis of CSU for at least six months prior to randomization and who are refractory to H1AH treatment. Both genders are represented, and the study includes a vulnerable population. Participants are required to adhere to specific lifestyle considerations, such as maintaining reliable contraceptive precautions if applicable. The trial does not specify any particular dietary or physical activity requirements beyond the general health status of the participants, which is not detailed in the provided data.

The clinical trial is a **Phase 3**, randomized, double-blind, parallel-group, multicenter study designed to evaluate the efficacy, safety, pharmacodynamics, pharmacokinetics, and immunogenicity of BP11 compared to EU-approved Xolair in patients with **chronic spontaneous urticaria** who are resistant to H1 antagonist treatment. The trial involves a comparison between BP11, Xolair, and a placebo, all administered as a solution for injection in pre-filled syringes via subcutaneous use. The study is expected to last until September 2025, with recruitment starting in October 2023.

Participants will be involved in the study for a maximum treatment period of 20 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility, baseline assessments, and regular follow-up visits at Weeks 2, 4, 8, 12, 16, 20, and 24. The primary endpoint is the change from baseline in the weekly Itch Severity Score (ISS7) at Week 12. Secondary endpoints include changes in the Urticaria Activity Score (UAS7), Hives Severity Score (HSS7), and Dermatology Life Quality Index (DLQI), as well as the incidence of adverse events and the presence of antidrug antibodies.

Participants are required to maintain an electronic diary to record symptoms and medication use, which is crucial for data collection. The study will monitor physical examinations, vital signs, electrocardiograms, and laboratory parameters throughout the trial. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that compromise participant safety.

The clinical trial involves the administration of three different treatments to evaluate their efficacy, safety, pharmacodynamics, pharmacokinetics, and immunogenicity in patients with **chronic spontaneous urticaria** who are resistant to H1 antagonist therapy. The experimental medication, BP11, is a **solution for injection** in a pre-filled syringe containing the active substance **omalizumab**. It is manufactured by Curateq Biologics Private Ltd. BP11 is administered via **subcutaneous use** with a maximum daily dose of 300 mg and a total maximum dose of 1800 mg over a treatment period of 20 weeks. The formulation is not specifically designed for pediatric use.

The comparator treatment in the study is Xolair, a 150 mg solution for injection in a pre-filled syringe, also containing the active substance omalizumab. Xolair is produced by Novartis Europharm Limited and is administered subcutaneously. The dosing schedule for Xolair mirrors that of BP11, with a maximum daily dose of 300 mg and a total maximum dose of 1800 mg over a 20-week period. This treatment is also not a pediatric formulation.

A placebo is used as a non-experimental treatment in this study. The placebo is a solution for injection in a pre-filled syringe, designed to mimic the administration of the active treatments without containing any active substance. The placebo is administered subcutaneously, following the same schedule as the active treatments to maintain the study's double-blind design. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the therapeutic equivalence between BP11 and Xolair in patients with **chronic spontaneous urticaria** (CSU) who are resistant to H1 antagonist treatment. The primary endpoint is the change from baseline in the weekly Itch Severity Score (ISS7) at Week 12. Secondary endpoints include changes from baseline in ISS7 at Weeks 2, 4, 8, 16, 20, and 24, as well as changes in the weekly Urticaria Activity Score (UAS7) at the same time points. Additionally, the percentage of patients achieving a UAS7 score of ≤6 and the percentage of complete responders (UAS7 = 0) will be evaluated at these intervals.

Further secondary endpoints involve changes from baseline in the weekly Hives Severity Score (HSS7) and the overall Dermatology Life Quality Index (DLQI) score at specified weeks. The use of rescue medication and the incidence, nature, and severity of adverse events will also be monitored. Efficacy assessments will be conducted using patient-reported outcomes and validated scales, with data collection scheduled at multiple time points throughout the study, including Weeks 2, 4, 8, 12, 16, 20, and 24. The trial will also measure laboratory parameters, injection-site reactions, and the incidence of antidrug antibodies and neutralizing antibodies to omalizumab at designated intervals.