FAsenra Safety Trial in India

Study Overview
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Brief Summary
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Benralizumab is a humanised, afucosylated, monoclonal antibody that binds specifically to the human interlukin-5 (IL-5) receptor alpha subunit (IL-5Rα) of target cells such as eosinophils and basophils (Takatsu et al, 1994; Toba et al, 1999; Pelaia et al, 2020). Benralizumab was generally well tolerated by patients in clinical trials, with no apparent safety concerns. This study shall be conducted at 10 centers across India. The primary outcome measures will be Percentage of AEs a, SAEs, and TEAEs Nature, incidence, and severity of AEs including unexpected adverse drug reactions Percentage of patients with AEs that lead to study treatment discontinuations.

Detailed Description
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Fasenra (benralizumab) has been recently approved in India with the condition to conduct a Phase 4 postmarketing study in the Indian population, as previous studies did not include patients from India. This prospective postmarketing safety study is planned to meet the regulatory mandate and assess the safety of benralizumab treatment in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks. This interventional study will provide insights into the potential risks of eosinophil-lowering therapies when used in routine clinical care in India. The study will also evaluate the effectiveness of benralizumab in reducing asthma exacerbations. This is a prospective, single-arm, multicentre, interventional, Phase 4 study investigating the safety, tolerability, and effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks.

Official Title
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A Postmarketing, Phase 4, Multicentre, Prospective, Single-arm Study to Assess the Safety of Fasenra® (Benralizumab) in Adult Patients of Severe Asthma With Eosinophilic Phenotype in India.

Conditions
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In Adult Patients of Severe Asthma With Eosinophilic Phenotype in India

Intervention / Treatment
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* Biological: Benralizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18 to 75 years of age inclusive, at the time of signing the informed consent Patients with physician's confirmed diagnosis of severe asthma with an eosinophilic phenotype, ie, a diagnosis of severe asthma in preceding at least 12 months, with an eosinophil count of ≥300 cells/μL at screening, requiring treatment with high-dose ICS (>500 μg fluticasone propionate dry powder formulation, or >800 μg budesonide dry powder formulation, or equivalent total daily dose) and a LABA as maintenance treatment for at least 3 months prior to enrolment A decreased lung function with prebronchodilator (Pre-BD) forced expiratory volume in 1 second (FEV1) of <80% predicted, demonstrated by spirometry at screening At least 2 documented asthma exacerbations in the preceeding12 months, except in 30 days before the date of informed consent, that required the use of a systemic corticosteroid or temporary increase from the patient's usual maintenance dose of oral corticosteroid (OCS) Documented postbronchodilator (post-BD) reversibility in FEV1 of ≥12% and ≥200 mL in FEV1 within 12 months before first dose. If historical documentation is not available, reversibility must be demonstrated and documented at screening or Day 1 before first dose Benralizumab naïve patients who have not previously received benralizumab prior to the start of this study Patients who are willing and capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: Clinically important pulmonary disease other than asthma (eg, active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis etc.) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome), which can confound the outcome assessment. Patients currently enrolled in an interventional clinical study in parallel including those with any biologic treatment Patients who have received any biologic within 30 days prior to the date of informed consent. Known history of allergy or reaction to the benralizumab formulation or excipients (L-histidine, L-histidine hydrochloride monohydrate, α-trehalose dihydrate, polysorbate 20, water for injection) History of anaphylaxis to any biologic therapy A helminth parasitic infection diagnosed within 24 weeks before the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy Acute asthma exacerbation 30 days before the date informed consent Acute asthma exacerbation between screening and first dose of study dose administration. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days before the date informed consent Patients with malignancy within 5 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal, or squamous cell carcinoma or non-melanomatous skin cancer with active or recent malignancy Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis, which, in the opinion of the investigator, may put the participant at risk because of his/her participation in the study History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the participant's full participation in the study, in the opinion of the investigator Female patients who are pregnant or lactating or planning a family during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective, single-arm, multicentre, interventional, Phase 4 study investigating the safety, tolerability, and effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Benralizumab<br>Single arm, Phase-IV | Biological: Benralizumab<br>* Prospective, Single-arm Study to Assess the Safety of Fasenra® (Benralizumab) in Adult Patients of Severe Asthma with Eosinophilic Phenotype in India<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | Number of incidence of adverse events (AEs) and serious adverse events (SAEs) | up to 24 weeks | 
| To assess the safety and tolerability of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | Frequency of incidence of adverse events (AEs) and serious adverse events (SAEs) | up to 24 weeks | 
| To assess the safety and tolerability of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | Percentages of incidence of adverse events (AEs) and serious adverse events (SAEs) | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | Time to first asthma exacerbation | up to 24 weeks | 
| To assess the effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | annualised exacerbation rate | up to 24 weeks | 
| To assess the effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | overall investigator's assessment on the outcome of the treatment: well controlled, partly controlled, uncontrolled | Up to 24 weeks | 
| To assess the effectiveness of Fasenra (benralizumab) in adult patients of severe asthma with eosinophilic phenotype over a period of 24 weeks | change in blood eosinophil levels from baseline at Weeks 4, 16, and 24 | Up to24 weeks |