A Phase 2 interventional study of Placebo and Benralizumab in Asthma, sponsored by MedImmune LLC. Completed at 11 sites in 2 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2020-11-18.
Sponsored by MedImmune LLC · Phase 2, Interventional, and Treatment
The study will evaluate the effect of two intravenous dose regimens of benralizumab (MEDI-563) on the proportion of adult subjects with asthma exacerbations who required an urgent healthcare visit for treatment of an acute asthma exacerbation.
The study will evaluate the effect of two intravenous dose regimens of benralizumab (MEDI-563) (0.3 milligram per kilogram [mg/kg] of body weight and 1.0 mg/kg of body weight) on the proportion of adult subjects with asthma exacerbations (relapse and de novo) who required an urgent healthcare visit for treatment of an acute asthma exacerbation.
3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.
This study's enrollment of 110 is above the median of 83 across 2,752 interventional studies indexed under Asthma.
Browse Asthma studies →MedImmune LLC is the lead sponsor of 265 studies on the registry; none are open to participants now.
Of its 50 completed or terminated interventional studies of FDA-regulated products, 28 (56%) have results posted.
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Exclusion Criteria:
A single dose of placebo matched to benralizumab (MEDI-563) intravenous infusion over at least 30 minutes on Day 0.
Other: Placebo
A single dose of benralizumab (MEDI-563) 0.3 milligram per kilogram (mg/kg) of body weight intravenous infusion over at least 30 minutes on Day 0.
Biological: Benralizumab
A single dose of benralizumab (MEDI-563) 1.0 mg/kg of body weight intravenous infusion over at least 30 minutes on Day 0.
Biological: Benralizumab
A single dose of placebo matched to benralizumab (MEDI-563) intravenous infusion over at least 30 minutes on Day 0.
A single dose of benralizumab (MEDI-563) 0.3 or 1 mg/kg of body weight intravenous infusion over at least 30 minutes on Day 0.
Also known as: MEDI-563
Percentage of Participants With Asthma Exacerbations at Week 12
Percentage of participants who required urgent healthcare visit for treatment of acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse/de novo) was defined as either 1) increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during scheduled study visit, participant had acute worsening of asthma symptoms and a reduction of greater than or equal to (\>=) 20 percent (%) in Peak Expiratory Flow (PEF) or Forced Expiratory Volume in 1 Second (FEV1), which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.
Time frame: Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 84 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Day 0 to Day 84
Percentage of Participants With Asthma Exacerbations at Week 4 and Week 24
Percentage of participants who required an urgent healthcare visit for treatment of an acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse or de novo) was defined as either 1) an increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after the use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during a scheduled study visit, the participant had acute worsening of asthma symptoms and a reduction of \>=20% in PEF or FEV1, which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.
Time frame: Weeks 4 and 24
Asthma Control Questionnaire (ACQ) Scores
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Results were reported for overall ACQ score and 6 item scores.
Time frame: Days 0, 7, 42, and 84
Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites
The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Spirometry was performed with the participant in the sitting position at study sites by the investigator or qualified designee according to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Multiple forced expiratory efforts (at least 2 but no more than 5) were performed for each office spirometry session and the 2 best efforts that met ATS/ERS acceptability and reproducibility criteria were recorded. The best efforts were based on the highest FEV1. The maximum FEV1 of the 2 best efforts was used for the analysis.
Time frame: Days 0, 7, 42, and 84
Forced Expiratory Volume in 1 Second (FEV1) Recorded at Home
The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Home peak flow testing for FEV1 was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean FEV1 values for each week were reported starting from Day 1 to Day 84.
Time frame: Day 1 to Day 84
Peak Expiratory Flow (PEF) Recorded at Home
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Home peak flow testing for PEF was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean PEF values for each week were reported starting from Day 1 to Day 84.
Time frame: Day 1 to Day 84
Number of Puffs of Rescue Beta-2 Agonist Per Week
Rescue beta-2 agonist use (total number of puffs for the prior day) was collected daily in the morning by the participants in the electronic daily diary provided to them. Participants were instructed not to collect rescue beta-2 agonist used prior to exercise. Average values for each week were reported starting from Day 1 to Day 84.
Time frame: Day 1 to Day 84
Number of Participants With Physician Global Assessment (PGA) at Day 42 and Day 84
Physician Global Assessment (PGA) consisted of a single physician-rated question assessing participant's status as 'excellent', 'good', 'moderate', 'poor', 'worsening' or 'not applicable (NA)'. Number of participants were categorically summarized.
Time frame: Days 42 and 84
Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores
Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ\[S\]): a 32-item questionnaire that measures the functional impairments experienced by adult participants including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment).
Time frame: Days 0, 42, and 84
Number of Healthcare Resources Utilized by Resource Type
Healthcare resource use was summarized by resource type from information on asthma exacerbations, and asthma related medications. Healthcare resource utilization assessed the total number of hospitalizations, urgent care, primary care clinic visits, asthma specialist clinic visits, telephone calls, and home management.
Time frame: Day 0 to Day 168
Maximum Observed Serum Concentration (Cmax) for Benralizumab
The Cmax of benralizumab is reported. Non-compartmental pharmacokinetic (PK) analysis was used for evaluation.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Area Under the Serum Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) for Benralizumab
AUClast = area under the concentration-time curve from time 0 to last measurable concentration. Non-compartmental PK analysis was used for evaluation.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Area Under the Serum Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUC [0 - Infinity]) for Benralizumab
AUC \[0 - infinity\] = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). Non-compartmental PK analysis was used for evaluation.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Systemic Clearance (CL) for Benralizumab
Systemic clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Non-compartmental PK analysis was used for evaluation. Clearance was normalized to participant's body weight.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Terminal Phase Elimination Half-Life (t1/2) for Benralizumab
Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half. Non-compartmental PK analysis was used for evaluation.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Volume of Distribution of the Central Compartment (Vc) for Benralizumab
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vc = volume of distribution of the central compartment, calculated as Dose/Cmax; where Cmax = maximum observed serum concentration. Non-compartmental PK analysis was used for evaluation. Results were normalized to participant's body weight.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Volume of Distribution at Steady State (Vss) for Benralizumab
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vss = steady state volume of distribution, calculated as MRT\*CL, where MRT is the Mean Residence Time and CL is systemic clearance; which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Non-compartmental PK analysis was used for evaluation. Results were normalized to participant's body weight.
Time frame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
Number of Participants With Anti-Drug Antibodies to Benralizumab
Number of participants with anti-drug antibodies to benralizumab is reported.
Time frame: Day 0 and 84
A total of 110 participants were randomized in the study.
| Milestone | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Started | 38 | 36 | 36 |
| Completed | 36 | 35 | 32 |
| Not completed | 2 | 1 | 4 |
| Withdrew: Lost to follow-up | 2 | 0 | 4 |
| Withdrew: Participant incarcerated | 0 | 1 | 0 |
Percentage of participants who required urgent healthcare visit for treatment of acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse/de novo) was defined as either 1) increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during scheduled study visit, participant had acute worsening of asthma symptoms and a reduction of greater than or equal to (\>=) 20 percent (%) in Peak Expiratory Flow (PEF) or Forced Expiratory Volume in 1 Second (FEV1), which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.
| percentage of participants | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Non-adjudicated Exacerbations | 38.9 | 25.0 | 41.7 |
| Adjudicated Exacerbations | 38.9 | 25.0 | 41.7 |
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 84 that were absent before treatment or that worsened relative to pretreatment state.
| Participants | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| TEAEs | 30 | 32 | 30 |
| TESAEs | 9 | 8 | 11 |
Percentage of participants who required an urgent healthcare visit for treatment of an acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse or de novo) was defined as either 1) an increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after the use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during a scheduled study visit, the participant had acute worsening of asthma symptoms and a reduction of \>=20% in PEF or FEV1, which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.
| percentage of participants | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Week 4: Non-adjudicated Exacerbations | 22.2 | 11.1 | 22.2 |
| Week 4: Adjudicated Exacerbations | 22.2 | 11.1 | 22.2 |
| Week 24: Non-adjudicated Exacerbations | 47.2 | 36.1 | 50.0 |
| Week 24: Adjudicated Exacerbations | 47.2 | 36.1 | 50.0 |
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Results were reported for overall ACQ score and 6 item scores.
| units on a scale | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Overall ACQ: Day 0 | 3.69 ± 0.82 | 3.72 ± 1.18 | 3.26 ± 1.27 |
| Overall ACQ: Day 7 | 1.89 ± 1.16 | 1.89 ± 1.36 | 1.52 ± 0.96 |
| Overall ACQ: Day 42 | 1.70 ± 1.23 | 1.76 ± 1.25 | 1.50 ± 1.13 |
| Overall ACQ: Day 84 | 1.59 ± 1.23 | 1.75 ± 1.33 | 1.70 ± 1.12 |
| Night-time waking: Day 0 | 3.1 ± 1.4 | 3.5 ± 1.8 | 2.9 ± 1.7 |
| Night-time waking: Day 7 | 1.7 ± 1.6 | 1.7 ± 1.7 | 1.0 ± 1.0 |
| Night-time waking: Day 42 | 1.4 ± 1.6 | 1.6 ± 1.5 | 1.2 ± 1.4 |
| Night-time waking: Day 84 | 1.3 ± 1.4 | 1.4 ± 1.6 | 1.2 ± 1.2 |
| Symptoms on waking: Day 0 | 3.4 ± 1.4 | 3.5 ± 1.5 | 2.8 ± 1.5 |
| Symptoms on waking: Day 7 | 1.8 ± 1.3 | 2.0 ± 1.4 | 1.4 ± 1.2 |
| Symptoms on waking: Day 42 | 1.6 ± 1.3 | 1.6 ± 1.3 | 1.2 ± 1.0 |
| Symptoms on waking: Day 84 | 1.5 ± 1.6 | 1.7 ± 1.4 | 1.6 ± 1.2 |
| Activity limitation: Day 0 | 3.6 ± 1.3 | 3.5 ± 1.4 | 3.2 ± 1.8 |
| Activity limitation: Day 7 | 1.7 ± 1.3 | 1.8 ± 1.5 | 1.5 ± 1.5 |
| Activity limitation: Day 42 | 1.6 ± 1.5 | 1.6 ± 1.5 | 1.4 ± 1.3 |
| Activity limitation: Day 84 | 1.3 ± 1.3 | 1.5 ± 1.3 | 2.0 ± 1.9 |
| Shortness of breath: Day 0 | 4.4 ± 1.0 | 4.2 ± 1.3 | 3.7 ± 1.5 |
| Shortness of breath: Day 7 | 1.9 ± 1.4 | 2.1 ± 1.5 | 1.8 ± 1.4 |
| Shortness of breath: Day 42 | 2.0 ± 1.3 | 2.1 ± 1.5 | 1.9 ± 1.5 |
| Shortness of breath: Day 84 | 1.8 ± 1.3 | 2.0 ± 1.4 | 1.9 ± 1.4 |
| Wheeze: Day 0 | 4.5 ± 1.1 | 4.2 ± 1.5 | 4.0 ± 1.6 |
| Wheeze: Day 7 | 2.6 ± 1.9 | 2.2 ± 1.6 | 2.0 ± 1.8 |
| Wheeze: Day 42 | 2.1 ± 1.5 | 2.0 ± 1.5 | 1.8 ± 1.5 |
| Wheeze: Day 84 | 2.1 ± 1.7 | 2.2 ± 1.7 | 1.8 ± 1.6 |
| Rescue beta-2 agonist use: Day 0 | 3.0 ± 1.3 | 3.3 ± 1.6 | 3.2 ± 1.5 |
| Rescue beta-2 agonist use: Day 7 | 1.7 ± 1.1 | 1.6 ± 1.5 | 1.3 ± 0.9 |
| Rescue beta-2 agonist use: Day 42 | 1.5 ± 1.3 | 1.6 ± 1.3 | 1.6 ± 1.6 |
| Rescue beta-2 agonist use: Day 84 | 1.5 ± 1.2 | 1.7 ± 1.4 | 1.8 ± 1.3 |
The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Spirometry was performed with the participant in the sitting position at study sites by the investigator or qualified designee according to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Multiple forced expiratory efforts (at least 2 but no more than 5) were performed for each office spirometry session and the 2 best efforts that met ATS/ERS acceptability and reproducibility criteria were recorded. The best efforts were based on the highest FEV1. The maximum FEV1 of the 2 best efforts was used for the analysis.
| liters | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Day 0 | 1.696 ± 0.523 | 1.689 ± 0.698 | 2.067 ± 0.746 |
| Day 7 | 2.008 ± 0.632 | 2.003 ± 0.655 | 2.254 ± 0.723 |
| Day 42 | 1.962 ± 0.714 | 2.130 ± 0.713 | 2.150 ± 0.723 |
| Day 84 | 2.048 ± 0.761 | 2.043 ± 0.710 | 2.209 ± 0.791 |
The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Home peak flow testing for FEV1 was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean FEV1 values for each week were reported starting from Day 1 to Day 84.
| liters | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Day 1 to 7 | 1.6346 ± 0.4868 | 1.7119 ± 0.6309 | 1.8404 ± 0.7222 |
| Day 8 to 14 | 1.7800 ± 0.5608 | 1.8562 ± 0.6467 | 1.7674 ± 0.7305 |
| Day 15 to 21 | 1.7024 ± 0.5200 | 1.7874 ± 0.6529 | 1.8219 ± 0.7241 |
| Day 22 to 28 | 1.6751 ± 0.5814 | 1.8188 ± 0.6461 | 1.8351 ± 0.7107 |
| Day 29 to 35 | 1.6446 ± 0.4962 | 1.7937 ± 0.6229 | 1.7486 ± 0.7093 |
| Day 36 to 42 | 1.7230 ± 0.5844 | 1.7935 ± 0.6341 | 1.7298 ± 0.6923 |
| Day 43 to 49 | 1.7326 ± 0.5426 | 1.7999 ± 0.6735 | 1.7803 ± 0.6655 |
| Day 50 to 56 | 1.6965 ± 0.5756 | 1.7532 ± 0.6530 | 1.7806 ± 0.6558 |
| Day 57 to 63 | 1.6600 ± 0.6013 | 1.7682 ± 0.6619 | 1.8504 ± 0.7636 |
| Day 64 to 70 | 1.7218 ± 0.6308 | 1.8735 ± 0.7701 | 1.7904 ± 0.7959 |
| Day 71 to 77 | 1.7180 ± 0.5969 | 1.7811 ± 0.6721 | 1.7401 ± 0.6891 |
| Day 78 to 84 | 1.7591 ± 0.6944 | 1.6655 ± 0.6032 | 1.7818 ± 0.7009 |
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Home peak flow testing for PEF was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean PEF values for each week were reported starting from Day 1 to Day 84.
| liters per minute (L/min) | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Day 1 to 7 | 161.845 ± 45.186 | 179.000 ± 61.653 | 177.929 ± 58.791 |
| Day 8 to 14 | 175.093 ± 50.914 | 186.538 ± 52.945 | 172.811 ± 59.941 |
| Day 15 to 21 | 169.489 ± 51.560 | 180.627 ± 55.853 | 180.362 ± 60.894 |
| Day 22 to 28 | 163.844 ± 57.753 | 183.066 ± 54.902 | 181.199 ± 62.497 |
| Day 29 to 35 | 163.999 ± 53.078 | 179.064 ± 55.297 | 171.458 ± 65.889 |
| Day 36 to 42 | 169.510 ± 57.745 | 178.373 ± 51.881 | 168.228 ± 64.673 |
| Day 43 to 49 | 171.373 ± 56.824 | 185.847 ± 57.767 | 169.727 ± 65.110 |
| Day 50 to 56 | 169.487 ± 58.325 | 178.070 ± 57.414 | 169.230 ± 62.696 |
| Day 57 to 63 | 169.723 ± 61.318 | 176.761 ± 56.410 | 169.374 ± 70.249 |
| Day 64 to 70 | 166.968 ± 57.401 | 188.805 ± 59.186 | 164.368 ± 66.619 |
| Day 71 to 77 | 160.717 ± 61.017 | 175.379 ± 59.158 | 160.167 ± 59.618 |
| Day 78 to 84 | 167.197 ± 58.690 | 172.788 ± 56.722 | 164.982 ± 60.271 |
Rescue beta-2 agonist use (total number of puffs for the prior day) was collected daily in the morning by the participants in the electronic daily diary provided to them. Participants were instructed not to collect rescue beta-2 agonist used prior to exercise. Average values for each week were reported starting from Day 1 to Day 84.
| puffs per week | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Day 1 to 7 | 1.95 ± 1.75 | 1.74 ± 2.05 | 1.47 ± 1.76 |
| Day 8 to 14 | 1.80 ± 2.01 | 1.63 ± 1.90 | 1.38 ± 2.07 |
| Day 15 to 21 | 1.57 ± 2.00 | 2.01 ± 3.34 | 1.42 ± 1.70 |
| Day 22 to 28 | 1.93 ± 2.65 | 1.83 ± 2.55 | 1.45 ± 1.76 |
| Day 29 to 35 | 1.76 ± 2.79 | 1.62 ± 2.17 | 1.53 ± 1.73 |
| Day 36 to 42 | 1.86 ± 3.36 | 1.42 ± 1.65 | 1.59 ± 1.92 |
| Day 43 to 49 | 1.85 ± 3.53 | 1.33 ± 1.44 | 1.71 ± 2.05 |
| Day 50 to 56 | 2.16 ± 4.83 | 1.52 ± 1.94 | 1.87 ± 2.32 |
| Day 57 to 63 | 2.59 ± 6.63 | 1.43 ± 1.73 | 1.54 ± 1.56 |
| Day 64 to 70 | 2.69 ± 6.43 | 1.50 ± 1.76 | 1.48 ± 1.65 |
| Day 71 to 77 | 1.69 ± 1.96 | 1.39 ± 1.84 | 1.48 ± 1.44 |
| Day 78 to 84 | 1.27 ± 1.56 | 2.04 ± 3.11 | 1.47 ± 1.41 |
Physician Global Assessment (PGA) consisted of a single physician-rated question assessing participant's status as 'excellent', 'good', 'moderate', 'poor', 'worsening' or 'not applicable (NA)'. Number of participants were categorically summarized.
| Participants | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Day 42: Excellent | 9 | 10 | 10 |
| Day 42: Good | 12 | 19 | 16 |
| Day 42: Moderate | 8 | 3 | 7 |
| Day 42: Poor | 3 | 3 | 2 |
| Day 42: Worsening | 1 | 1 | 0 |
| Day 42: Not applicable | 1 | 0 | 1 |
| Day 84: Excellent | 8 | 12 | 11 |
| Day 84: Good | 15 | 13 | 11 |
| Day 84: Moderate | 7 | 3 | 9 |
| Day 84: Poor | 3 | 4 | 1 |
| Day 84: Worsening | 2 | 3 | 0 |
| Day 84: Not applicable | 1 | 0 | 0 |
Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ\[S\]): a 32-item questionnaire that measures the functional impairments experienced by adult participants including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment).
| units on a scale | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Overall: Day 0 | 3.14 ± 0.91 | 3.18 ± 0.95 | 3.35 ± 1.11 |
| Overall: Day 42 | 4.74 ± 1.65 | 4.76 ± 1.46 | 5.16 ± 1.44 |
| Overall: Day 84 | 4.91 ± 1.71 | 5.01 ± 1.44 | 5.11 ± 1.35 |
| Symptoms: Day 0 | 2.84 ± 0.94 | 2.79 ± 1.08 | 3.11 ± 1.25 |
| Symptoms: Day 42 | 4.77 ± 1.82 | 4.82 ± 1.45 | 5.19 ± 1.62 |
| Symptoms: Day 84 | 4.94 ± 1.68 | 4.95 ± 1.53 | 5.09 ± 1.36 |
| Activity limitation: Day 0 | 3.56 ± 0.97 | 3.74 ± 1.13 | 3.98 ± 1.29 |
| Activity limitation: Day 42 | 4.96 ± 1.54 | 4.92 ± 1.51 | 5.30 ± 1.42 |
| Activity limitation: Day 84 | 5.11 ± 1.74 | 5.23 ± 1.36 | 5.24 ± 1.44 |
| Emotional function: Day 0 | 2.73 ± 1.25 | 2.44 ± 1.16 | 2.47 ± 1.48 |
| Emotional function: Day 42 | 4.30 ± 1.96 | 4.35 ± 1.77 | 4.91 ± 1.66 |
| Emotional function: Day 84 | 4.59 ± 2.04 | 4.59 ± 1.75 | 4.84 ± 1.73 |
| Environmental stimuli: Day 0 | 3.35 ± 1.31 | 3.72 ± 1.29 | 3.42 ± 1.48 |
| Environmental stimuli: Day 42 | 4.59 ± 1.69 | 4.63 ± 1.53 | 4.99 ± 1.44 |
| Environmental stimuli: Day 84 | 4.69 ± 1.80 | 5.08 ± 1.62 | 5.13 ± 1.35 |
Healthcare resource use was summarized by resource type from information on asthma exacerbations, and asthma related medications. Healthcare resource utilization assessed the total number of hospitalizations, urgent care, primary care clinic visits, asthma specialist clinic visits, telephone calls, and home management.
| healthcare resources | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| Hospitalizations | 64 | 40 | 43 |
| Urgent care | 2 | 0 | 0 |
| Primary care clinic visits | 3 | 1 | 5 |
| Asthma specialist clinic visits | 5 | 5 | 0 |
| Telephone calls | 6 | 1 | 4 |
| Home management | 2 | 1 | 4 |
The Cmax of benralizumab is reported. Non-compartmental pharmacokinetic (PK) analysis was used for evaluation.
| microgram per milliliter (mcg/mL) | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) for Benralizumab | 7.03 ± 1.78 | 26.7 ± 6.49 |
AUClast = area under the concentration-time curve from time 0 to last measurable concentration. Non-compartmental PK analysis was used for evaluation.
| microgram*day per milliliter | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Area Under the Serum Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) for Benralizumab | 65.7 ± 18.5 | 263 ± 64.1 |
AUC \[0 - infinity\] = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). Non-compartmental PK analysis was used for evaluation.
| microgram*day per milliliter | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Area Under the Serum Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUC [0 - Infinity]) for Benralizumab | 67.1 ± 18.0 | 268 ± 65.7 |
Systemic clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Non-compartmental PK analysis was used for evaluation. Clearance was normalized to participant's body weight.
| milliliter per kilogram per day | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Systemic Clearance (CL) for Benralizumab | 4.92 ± 1.96 | 3.97 ± 1.02 |
Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half. Non-compartmental PK analysis was used for evaluation.
| days | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Terminal Phase Elimination Half-Life (t1/2) for Benralizumab | 11.5 ± 3.14 | 13.2 ± 2.39 |
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vc = volume of distribution of the central compartment, calculated as Dose/Cmax; where Cmax = maximum observed serum concentration. Non-compartmental PK analysis was used for evaluation. Results were normalized to participant's body weight.
| milliliter per kilogram (mL/kg) | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Volume of Distribution of the Central Compartment (Vc) for Benralizumab | 46.4 ± 17.0 | 39.8 ± 10.3 |
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vss = steady state volume of distribution, calculated as MRT\*CL, where MRT is the Mean Residence Time and CL is systemic clearance; which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Non-compartmental PK analysis was used for evaluation. Results were normalized to participant's body weight.
| mL/kg | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Volume of Distribution at Steady State (Vss) for Benralizumab | 71.8 ± 23.2 | 64.0 ± 15.1 |
Number of participants with anti-drug antibodies to benralizumab is reported.
| Participants | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|
| Day 0 | 1 | 0 |
| Day 84 | 2 | 4 |
Collected over Day 0 to Day 84. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/38 (0%) | 9/38 (23.7%) | 28/38 (73.7%) |
| Benralizumab 0.3 mg/kg | 0/36 (0%) | 8/36 (22.2%) | 30/36 (83.3%) |
| Benralizumab 1.0 mg/kg | 0/36 (0%) | 11/36 (30.6%) | 28/36 (77.8%) |
| Event | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| AsthmaRespiratory, thoracic and mediastinal disorders | 9/38 | 4/36 | 6/36 |
| TachycardiaCardiac disorders | 0/38 | 0/36 | 1/36 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 0/38 | 1/36 | 0/36 |
| OesophagitisGastrointestinal disorders | 0/38 | 1/36 | 0/36 |
| PyrexiaGeneral disorders | 0/38 | 1/36 | 1/36 |
| GastroenteritisInfections and infestations | 0/38 | 0/36 | 1/36 |
| PneumoniaInfections and infestations | 0/38 | 1/36 | 0/36 |
| Post procedural complicationInjury, poisoning and procedural complications | 0/38 | 0/36 | 1/36 |
| Diabetes mellitusMetabolism and nutrition disorders | 0/38 | 1/36 | 0/36 |
| AnxietyPsychiatric disorders | 0/38 | 0/36 | 1/36 |
| Event | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg |
|---|---|---|---|
| AsthmaRespiratory, thoracic and mediastinal disorders | 18/38 | 12/36 | 14/36 |
| HeadacheNervous system disorders | 4/38 | 5/36 | 9/36 |
| CoughRespiratory, thoracic and mediastinal disorders | 3/38 | 1/36 | 6/36 |
| DizzinessNervous system disorders | 1/38 | 5/36 | 3/36 |
| DyspepsiaGastrointestinal disorders | 0/38 | 3/36 | 0/36 |
| NauseaGastrointestinal disorders | 1/38 | 0/36 | 3/36 |
| Blood creatinine increasedInvestigations | 0/38 | 0/36 | 3/36 |
| BronchitisInfections and infestations | 3/38 | 2/36 | 2/36 |
| Upper respiratory tract infectionInfections and infestations | 3/38 | 1/36 | 0/36 |
| Back painMusculoskeletal and connective tissue disorders | 3/38 | 0/36 | 2/36 |
Intent-to-treat population included all participants who were randomized into the study.
| Age, Continuous(Years) | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg | Total |
|---|---|---|---|---|
| Mean | 35.9 ± 10.5 | 37.9 ± 11.4 | 34.8 ± 10.0 | 36.2 ± 10.6 |
| Sex: Female, Male(Participants) | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg | Total |
|---|---|---|---|---|
| Female | 30 | 24 | 23 | 77 |
| Male | 8 | 12 | 13 | 33 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg | Total |
|---|---|---|---|---|
| Hispanic or Latino | 6 | 2 | 7 | 15 |
| Not Hispanic or Latino | 32 | 34 | 29 | 95 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Placebo | Benralizumab 0.3 mg/kg | Benralizumab 1.0 mg/kg | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 0 | 1 |
| Asian | 0 | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 26 | 19 | 19 | 64 |
| White | 11 | 14 | 16 | 41 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 2 | 1 | 3 |
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