In Adult Patients of Severe Asthma With Eosinophilic Phenotype in India
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALBenralizumab
Prospective, Single-arm Study to Assess the Safety of Fasenra® (Benralizumab) in Adult Patients of Severe Asthma with Eosinophilic Phenotype in India
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients 18 to 75 years of age inclusive, at the time of signing the informed consent 2. 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 3. A decreased lung function with prebronchodilator (Pre-BD) forced expiratory volume in 1 second (FEV1) of \<80% predicted, demonstrated by spirometry at screening 4. 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) 5. 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 6. Benralizumab naïve patients who have not previously received benralizumab prior to the start of this study 7. 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
1. 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. 2. Patients currently enrolled in an interventional clinical study in parallel including those with any biologic treatment 3. Patients who have received any biologic within 30 days prior to the date of informed consent. 4. 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) 5. History of anaphylaxis to any biologic therapy 6. 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 7. Acute asthma exacerbation 30 days before the date informed consent 8. Acute asthma exacerbation between screening and first dose of study dose administration. 9. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days before the date informed consent 10. 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 11. 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 12. 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 13. Female patients who are pregnant or lactating or planning a family during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs | From study treatment to follow-up (up to 24 weeks) | The number and percentage of participants who experienced at least one adverse event (AE), serious AE, or treatment-emergent AE experienced are presented |
| Severity of AEs | From study treatment to follow-up (up to 24 weeks) | Severity of adverse events (AEs) by intensity grade |
| Participants With AEs That Led to Study Treatment Discontinuations or Modifications | From study treatment to follow-up (up to 24 weeks) | Participants with adverse events (AEs) that led to study treatment discontinuations or modifications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Investigators Assessment | From study treatment to follow-up (up to 24 weeks) | Overall investigator's assessment on the outcome of the treatment: well controlled, partly controlled, and uncontrolled. |
| Time to First Asthma Exacerbation | From study treatment to follow-up (up to 24 weeks) | Time to first asthma exacerbation in days in participants with asthma exacerbation |
| Change in Blood Eosinophil Levels From Baseline at Weeks 4, 16, and 24 | Baseline and Weeks 4, 16, and 24 | Mean change in blood eosinophil levels from baseline at Weeks 4, 16, and 24 |
| Exacerbation Rate: Before and After Treatment | From study treatment to follow-up (up to 24 weeks) | The annual exacerbation rate for each participant was calculated by dividing the total number of exacerbations by the number of days participated in the study and multiplying by 365. |
| Annualized Exacerbation Rate: Overall | From study treatment to follow-up (up to 24 weeks) | Overall annualized exacerbation rate. The annual exacerbation rate for each participant was calculated by dividing the total number of exacerbations by the number of days participated in the study and multiplying by 365. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab 30 mg/mL subcutaneous benralizumab once every 4 weeks for the first 3 doses, followed by a maintenance dosage of 30 mg/mL once every 8 weeks thereafter | 138 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | One participant included in study but not included in analysis as did not meet eligibility criteria | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Benralizumab |
|---|---|
| Age, Continuous | 47.7 Years STANDARD_DEVIATION 14.3 |
| Female, Indicate childbearing potential Postmenopausal female | 30 Participants |
| Female, Indicate childbearing potential Potentially able to bear children | 35 Participants |
| Female, Indicate childbearing potential Premenarchal | 0 Participants |
| Female, Indicate childbearing potential Premenopausal female | 6 Participants |
| Race/Ethnicity, Customized ASIAN | 138 Participants |
| Race/Ethnicity, Customized OTHER | 0 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 138 |
| other Total, other adverse events | 39 / 138 |
| serious Total, serious adverse events | 5 / 138 |
Outcome results
Primary
Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs
The number and percentage of participants who experienced at least one adverse event (AE), serious AE, or treatment-emergent AE experienced are presented
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab | Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs | Participants with at least one AE (including SAEs) | 44 Participants |
| Benralizumab | Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs | Participants with at least one serious AE | 5 Participants |
| Benralizumab | Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs | Participants with at least one treatment-emergent AE (including SAEs) | 43 Participants |
| Benralizumab | Participants With Adverse Events (AEs), Serious AEs, and Treatment-emergent AEs | Participants with at least one non-treatment-emergent and non-serious AE | 1 Participants |
Primary
Participants With AEs That Led to Study Treatment Discontinuations or Modifications
Participants with adverse events (AEs) that led to study treatment discontinuations or modifications
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benralizumab | Participants With AEs That Led to Study Treatment Discontinuations or Modifications | 0 Participants |
Primary
Severity of AEs
Severity of adverse events (AEs) by intensity grade
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab | Severity of AEs | Participants with at least one moderate AE | 16 Participants |
| Benralizumab | Severity of AEs | Participants with at least one severe AE | 1 Participants |
| Benralizumab | Severity of AEs | Participants with at least one mild AE | 33 Participants |
Secondary
Annualized Exacerbation Rate: Overall
Overall annualized exacerbation rate. The annual exacerbation rate for each participant was calculated by dividing the total number of exacerbations by the number of days participated in the study and multiplying by 365.
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Evaluable Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Benralizumab | Annualized Exacerbation Rate: Overall | 0.36 exacerbation events/year |
Secondary
Change in Blood Eosinophil Levels From Baseline at Weeks 4, 16, and 24
Mean change in blood eosinophil levels from baseline at Weeks 4, 16, and 24
Time frame: Baseline and Weeks 4, 16, and 24
Population: Evaluable Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab | Change in Blood Eosinophil Levels From Baseline at Weeks 4, 16, and 24 | Week 4 (Visit 2) | -511 cells/mm^3 | Standard Deviation 779.13 |
| Benralizumab | Change in Blood Eosinophil Levels From Baseline at Weeks 4, 16, and 24 | Week 16 (Visit 4) | -546 cells/mm^3 | Standard Deviation 867.79 |
| Benralizumab | Change in Blood Eosinophil Levels From Baseline at Weeks 4, 16, and 24 | Week 24 (Visit 5) | -541 cells/mm^3 | Standard Deviation 893.62 |
Comparison: Week 4 (Visit 2)p-value: <0.0001paired t-test
Comparison: Week 16 (Visit 4)p-value: <0.0001paired t-test
Comparison: Week 24 (Visit 5)p-value: <0.0001paired t-test
Secondary
Exacerbation Rate: Before and After Treatment
The annual exacerbation rate for each participant was calculated by dividing the total number of exacerbations by the number of days participated in the study and multiplying by 365.
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Evaluable Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab | Exacerbation Rate: Before and After Treatment | Exacerbation before study | 2.0 exacerbations events/year | Standard Deviation 0 |
| Benralizumab | Exacerbation Rate: Before and After Treatment | Exacerbation at end of study | 0.2 exacerbations events/year | Standard Deviation 0.47 |
Secondary
Overall Investigators Assessment
Overall investigator's assessment on the outcome of the treatment: well controlled, partly controlled, and uncontrolled.
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Evaluable Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab | Overall Investigators Assessment | Well controlled | 83 Participants |
| Benralizumab | Overall Investigators Assessment | Partly controlled | 45 Participants |
| Benralizumab | Overall Investigators Assessment | Uncontrolled | 7 Participants |
Secondary
Time to First Asthma Exacerbation
Time to first asthma exacerbation in days in participants with asthma exacerbation
Time frame: From study treatment to follow-up (up to 24 weeks)
Population: Evaluable Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab | Time to First Asthma Exacerbation | 112.6 days | Standard Deviation 50.45 |
Comparison: Estimate for Time to Response (Days)95% CI: [65, 160]