Asthma
Conditions
Brief summary
To study the effectiveness and safety of multiple-doses of MEDI-528 on asthma control in adult participants with uncontrolled, moderate-to-severe, persistent asthma.
Detailed description
The primary objective of this study is to evaluate the effect of multiple-dose subcutaneous (SC) administration of MEDI-528 on asthma control in adults with uncontrolled, moderate-to-severe, persistent asthma.
Interventions
BIOLOGICALMEDI528 30 mg
MEDI-528 at a dose of 30 mg administered as a subcutaneous injection every 2 weeks for 24 weeks
BIOLOGICALMEDI528 100 mg
MEDI-528 at a dose of 100 mg administered as a subcutaneous injection every 2 weeks for 24 weeks
BIOLOGICALMEDI528 300 mg
MEDI-528 at a dose of 300 mg administered as a subcutaneous injection every 2 weeks for 24 weeks
OTHERPlacebo
Placebo administered as a subcutaneous injection every 2 weeks for 24 weeks
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria: 1. Male or female 2. Age 18 through 65 years at the time of screening 3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 4. Female subjects of childbearing potential who are sexually active with non-sterilized male partner must use adequate contraception from screening through the end of the study. An acceptable method of contraception is defined as one that has no higher than a 1% failure rate. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception 1. Non-sterilized males who are sexually active with a female of child-bearing potential must use adequate contraception from screening through the end of the study 2. Females or female partners not of childbearing potential must have been surgically sterilized (eg, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as at least 1 year since last regular menses) 3. Sterilized males must be at least 1-year post vasectomy and have obtained documentation of the absence of sperm in the ejaculate 5. Weight ≥ 45 kg but ≤ 120 kg and body mass index (BMI) between 18 and 35 kg/m2 6. Physician-diagnosed asthma by medical chart 7. Currently taking inhaled corticosteroids (ICS) or is a candidate to receive ICS per Expert Panel Report (EPR)-3 8. Pre-bronchodilator forced expiratory volume in 1 second (FEV1) value ≥ 40% at Day -28 and Day 1 9. A post-bronchodilator increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL at Day -28 OR meeting any one of the following criteria: 1. Proof of post-bronchodilator reversibility of airflow obstruction ≥ 12% documented within 36 months prior to randomization or proof of a positive response to a methacholine challenge documented within 36 months prior to randomization; OR 2. Proof of partial reversibility of ≥ 8% to \< 12% improvement in post-bronchodilator FEV1 on Day -28 and achievement of ≥ 12% reversibility at a second time between Day -27 and Day -15; OR 3. If a) and b) are not met and all other inclusion/
Exclusion criteria
are met, subjects with a FEV1 of ≥ 1.5 L and ≥ 60% on Day -14 will be eligible to undergo a methacholine challenge. If the subject achieves a positive response to this methacholine challenge, then this criterion is met 10. Uncontrolled asthma consistent with EPR-3. In the 28 days before screening, subjects should have a history of one or more of the following: * Daytime asthma symptoms ≥ 2 days/week * Nighttime awakening ≥ 1 night/week * Albuterol/salbutamol use ≥ 2 days/week 11. An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at Day -28 and at Day 1. 12. At least one asthma exacerbation in the 12 months before screening that required intake of systemic corticosteroids after an unscheduled medical encounter or as agreed with a physician based on an asthma action plan that defines when oral steroids can be taken by the subject 13. Ability and willingness to complete the follow-up period through Day 323 as required by the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis) | Day 92 | Change at Day 92 from baseline (Day 1, prior to dosing) in mean ACQ scores in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis) | Days 1 - 176 | Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | Days 1 - 92 | The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | Days 1 - 176 | The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | Days 1 - 92 | Time to first asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | Days 1 - 176 | Time to first asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis) | Day 176 | Change at Day 176 from baseline (Day 1, prior to dosing) in mean ACQ scores in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | Day 92 | Proportion of participants achieving mean ACQ scores of \< or = 0.75, \> 0.75 to \< 1.5, and \> or = 1.5 at Day 92 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | Day 176 | Proportion of participants achieving mean ACQ scores of \< or = 0.75, \> 0.75 to \< 1.5, and \> or = 1.5 at Day 176 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis) | Days 1 - 92 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) \> or = 0.5 through Day 92 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis) | Days 1 - 92 | Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy. |
| Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | Day 92 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change at Day 92 from baseline (Day 1, prior to dosing) in FEV1. |
| Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | Day 176 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change from baseline (Day 1, prior to dosing) in FEV1 at Day 176 |
| Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis) | Day 85 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response (defined as an improvement of at least 0.5 score in AQLQ\[S\]) at Day 85 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, 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 is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes \> 1.5 identified to be large meaningful differences. |
| Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis) | Day 176 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response at Day 176 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, 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 is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes \> 1.5 identified to be large meaningful differences. |
| Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528 | Days 1, 29, 57, 85, 127, 169, 176, 204,260, and 323 | Proportion of participants with detectable anti-drug antibodies to MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528 and placebo |
| First Dose Trough Concentration of MEDI-528 | Day 15 | First dose trough concentration of MEDI-528 measured on Day 15 prior to administration of the second dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. The first dose trough concentration of MEDI-528 was measured on Day 15 prior to the Day 15 dose. |
| Day 169 Steady State Trough Concentration of MEDI-528 | Day 169 | Trough concentration of MEDI-528 measured on Day 169 prior to administration of the last dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. Steady state trough concentration of MEDI-528 was measured on Day 169. |
| Half Life of MEDI-528 | Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323 | Half life of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. |
| Accumulation Ratio of Trough Concentrations of MEDI-528 | Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323 | Accumulation ratio of trough concentrations of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. |
| Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis) | Days 1 - 176 | Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) \> or = 1.5 Through Day 176 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
Countries
Argentina, Brazil, Canada, Colombia, Costa Rica, Panama, Peru, Philippines, Taiwan, United States
Participant flow
Pre-assignment details
A total of 329 participants was randomized into the study, but 2 participants (1 in the MEDI-528 30 mg arm and 1 in the MEDI-528 300 mg arm) were randomized by mistake as they were screen failures. Therefore, a total of 327 participants were correctly randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered as a subcutaneous injection every 2 weeks for 24 weeks | 82 |
| MEDI528 30 mg MEDI-528 at a dose of 30 mg administered as a subcutaneous injection every 2 weeks for 24 weeks | 81 |
| MEDI528 100 mg MEDI-528 at a dose of 100 mg administered as a subcutaneous injection every 2 weeks for 24 weeks | 83 |
| MEDI528 300 mg MEDI-528 at a dose of 300 mg administered as a subcutaneous injection every 2 weeks for 24 weeks | 81 |
| Total | 327 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | AE | 1 | 0 | 0 | 0 |
| Overall Study | AE-TRANSITIONAL CELL TUMOR IN BLADDER | 0 | 0 | 0 | 1 |
| Overall Study | DID NOT MEET EXCLUSION CRITERIA | 1 | 0 | 0 | 0 |
| Overall Study | DUE TO REPEATED ASTHMA EXACERBATIONS | 1 | 0 | 0 | 0 |
| Overall Study | EARLY DISCONTINUED ON 10-DEC-2010 | 0 | 0 | 1 | 0 |
| Overall Study | EARLY WITHDRAWAL | 0 | 1 | 0 | 0 |
| Overall Study | ERROR IN HADS ADMINISTRATION | 0 | 0 | 1 | 0 |
| Overall Study | INEGIBILITY TO PERFORM VISIT | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 2 | 1 | 4 |
| Overall Study | PATIENT RECEIVE ORAL PREDNISONE | 0 | 1 | 0 | 0 |
| Overall Study | PATIENT WAS ENROLLED BY MISTAKE | 0 | 1 | 0 | 0 |
| Overall Study | PATIENT WAS RANDOMIZED BY MISTAKE | 0 | 1 | 0 | 0 |
| Overall Study | PATIENT WILL BE WORKING ABROAD | 0 | 1 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 2 | 0 |
| Overall Study | SPONSOR DECISION | 0 | 1 | 0 | 0 |
| Overall Study | SUBJECT COMPLETED SAFETY FOLLOW-UP | 0 | 0 | 1 | 0 |
| Overall Study | SUBJECT DID NOT MEET ACQ REQUIREMENT | 0 | 1 | 0 | 0 |
| Overall Study | SUBJECT INCARCERATED | 0 | 1 | 0 | 0 |
| Overall Study | SUBJECT WAS RANDOMIZED IN ERROR | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 5 | 3 |
| Overall Study | WITHDRAWN DUE TO PREDNISONE USE | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | MEDI528 30 mg | MEDI528 100 mg | MEDI528 300 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.6 Years STANDARD_DEVIATION 11.6 | 41.8 Years STANDARD_DEVIATION 11.1 | 45.1 Years STANDARD_DEVIATION 11.6 | 41.5 Years STANDARD_DEVIATION 12.3 | 43.0 Years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 53 Participants | 55 Participants | 62 Participants | 55 Participants | 225 Participants |
| Sex: Female, Male Male | 29 Participants | 26 Participants | 21 Participants | 26 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / 82 | 62 / 81 | 68 / 83 | 69 / 81 |
| serious Total, serious adverse events | 4 / 82 | 9 / 81 | 4 / 83 | 2 / 81 |
Outcome results
Primary
Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis)
Change at Day 92 from baseline (Day 1, prior to dosing) in mean ACQ scores in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Day 92
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 (n=81, 83, or 81, respectively) or placebo (n=82) groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis) | -1.23 Scores on a scale | Standard Deviation 0.95 |
| MEDI528 30 mg | Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis) | -1.10 Scores on a scale | Standard Deviation 1.11 |
| MEDI528 100 mg | Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis) | -1.26 Scores on a scale | Standard Deviation 1.02 |
| MEDI528 300 mg | Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis) | -1.31 Scores on a scale | Standard Deviation 1.07 |
p-value: 0.435ANOVA
p-value: 0.828ANOVA
p-value: 0.628ANOVA
Secondary
Accumulation Ratio of Trough Concentrations of MEDI-528
Accumulation ratio of trough concentrations of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323.
Time frame: Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81) and received at least one dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI528 30 mg | Accumulation Ratio of Trough Concentrations of MEDI-528 | 3.46 Ratio | Standard Deviation 1.53 |
| MEDI528 100 mg | Accumulation Ratio of Trough Concentrations of MEDI-528 | 4.18 Ratio | Standard Deviation 1.83 |
| MEDI528 300 mg | Accumulation Ratio of Trough Concentrations of MEDI-528 | 4.11 Ratio | Standard Deviation 1.99 |
Secondary
Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change from baseline (Day 1, prior to dosing) in FEV1 at Day 176
Time frame: Day 176
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 (n=81, 83, or 81, respectively) or placebo (n=82) groups who had FEV1 data available at Day 176 (n=67, 75, or 73 for 30, 100, or 300 mg MEDI-528, respectively, and n=69 for placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.044 Liters | Standard Deviation 0.367 |
| MEDI528 30 mg | Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | -0.005 Liters | Standard Deviation 0.324 |
| MEDI528 100 mg | Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.055 Liters | Standard Deviation 0.299 |
| MEDI528 300 mg | Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.047 Liters | Standard Deviation 0.29 |
p-value: 0.409Two-sample t-test
p-value: 0.847Two-sample t-test
p-value: 0.968Two-sample t-test
Secondary
Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis)
Change at Day 176 from baseline (Day 1, prior to dosing) in mean ACQ scores in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Day 176
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had ACQ data available on Day 176.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis) | -1.27 Scores on a scale | Standard Deviation 1.17 |
| MEDI528 30 mg | Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis) | -1.32 Scores on a scale | Standard Deviation 1.23 |
| MEDI528 100 mg | Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis) | -1.46 Scores on a scale | Standard Deviation 1.07 |
| MEDI528 300 mg | Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis) | -1.45 Scores on a scale | Standard Deviation 1.08 |
p-value: 0.813ANOVA
p-value: 0.29ANOVA
p-value: 0.303ANOVA
Secondary
Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change at Day 92 from baseline (Day 1, prior to dosing) in FEV1.
Time frame: Day 92
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 (n=81, 83, or 81, respectively) or placebo (n=82) groups who had FEV1 data available at Day 92 (n=62, 73, or 72 for 30, 100, or 300 mg MEDI-528, respectively, and n=67 for placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.033 Liters | Standard Deviation 0.326 |
| MEDI528 30 mg | Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.045 Liters | Standard Deviation 0.327 |
| MEDI528 100 mg | Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.048 Liters | Standard Deviation 0.23 |
| MEDI528 300 mg | Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis) | 0.097 Liters | Standard Deviation 0.29 |
p-value: 0.837Two-sample t-test
p-value: 0.756Two-sample t-test
p-value: 0.224Two-sample t-test
Secondary
Day 169 Steady State Trough Concentration of MEDI-528
Trough concentration of MEDI-528 measured on Day 169 prior to administration of the last dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. Steady state trough concentration of MEDI-528 was measured on Day 169.
Time frame: Day 169
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 group (n=81, 83, or 81, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI528 30 mg | Day 169 Steady State Trough Concentration of MEDI-528 | 5.99 Microgram per milliliter | Standard Deviation 3.37 |
| MEDI528 100 mg | Day 169 Steady State Trough Concentration of MEDI-528 | 21.68 Microgram per milliliter | Standard Deviation 9.49 |
| MEDI528 300 mg | Day 169 Steady State Trough Concentration of MEDI-528 | 61.57 Microgram per milliliter | Standard Deviation 26.85 |
Secondary
First Dose Trough Concentration of MEDI-528
First dose trough concentration of MEDI-528 measured on Day 15 prior to administration of the second dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. The first dose trough concentration of MEDI-528 was measured on Day 15 prior to the Day 15 dose.
Time frame: Day 15
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 group (n=81, 83, or 81, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI528 30 mg | First Dose Trough Concentration of MEDI-528 | 2.15 Microgram per milliliter | Standard Deviation 0.81 |
| MEDI528 100 mg | First Dose Trough Concentration of MEDI-528 | 5.91 Microgram per milliliter | Standard Deviation 2.97 |
| MEDI528 300 mg | First Dose Trough Concentration of MEDI-528 | 15.80 Microgram per milliliter | Standard Deviation 5.68 |
Secondary
Half Life of MEDI-528
Half life of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323.
Time frame: Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323
Population: All participants randomized into the 30, 100, or 300 mg MEDI-528 group (n=81, 83, or 81, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI528 30 mg | Half Life of MEDI-528 | 39.0 Days | Standard Deviation 8.14 |
| MEDI528 100 mg | Half Life of MEDI-528 | 32.6 Days | Standard Deviation 5.89 |
| MEDI528 300 mg | Half Life of MEDI-528 | 32.2 Days | Standard Deviation 6.41 |
Secondary
Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis)
Proportion of participants achieving mean ACQ scores of \< or = 0.75, \> 0.75 to \< 1.5, and \> or = 1.5 at Day 176 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Day 176
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had ACQ data available on Day 176.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 25 Participants |
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 38 Participants |
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 19 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 29 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 34 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 18 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 18 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 24 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 41 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 25 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 36 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 20 Participants |
Comparison: Combined MEDI-528 treatment was compared to placebop-value: 0.986Fisher Exact
Secondary
Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis)
Proportion of participants achieving mean ACQ scores of \< or = 0.75, \> 0.75 to \< 1.5, and \> or = 1.5 at Day 92 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Day 92
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had ACQ data available on Day 92.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 17 Participants |
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 42 Participants |
| Placebo | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 23 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 17 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 43 Participants |
| MEDI528 30 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 21 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 22 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 17 Participants |
| MEDI528 100 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 44 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | < or = 0.75 | 22 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > or = 1.5 | 43 Participants |
| MEDI528 300 mg | Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis) | > 0.75 and < 1.5 | 16 Participants |
Comparison: Combined MEDI-528 treatment was compared to placebop-value: 0.764Fisher Exact
Secondary
Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)
The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 176
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | 16 Participants | 0.15 |
| MEDI528 30 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | 17 Participants | 0.14 |
| MEDI528 100 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | 8 Participants | — |
| MEDI528 300 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | 15 Participants | — |
p-value: 0.8475Fisher Exact
p-value: 0.0811Fisher Exact
p-value: 1Fisher Exact
Secondary
Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)
The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 92
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | 8 Participants | 0.15 |
| MEDI528 30 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | 14 Participants | 0.14 |
| MEDI528 100 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | 5 Participants | — |
| MEDI528 300 mg | Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | 7 Participants | — |
p-value: 0.1764Fisher Exact
p-value: 0.4031Fisher Exact
p-value: 1Fisher Exact
Secondary
Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response at Day 176 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, 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 is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes \> 1.5 identified to be large meaningful differences.
Time frame: Day 176
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had AQLQ(S) data at Day 176 (n=62, 58, 64, and 60 for placebo, 30, 100, and 300 mg MEDI-528, respectively).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis) | 50 Participants | 57.871 |
| MEDI528 30 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis) | 42 Participants | 60.584 |
| MEDI528 100 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis) | 48 Participants | 53.11 |
| MEDI528 300 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis) | 46 Participants | 55.339 |
Comparison: Combined MEDI-528 dose groups versus placebop-value: 0.574Fisher Exact
Secondary
Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response (defined as an improvement of at least 0.5 score in AQLQ\[S\]) at Day 85 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, 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 is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes \> 1.5 identified to be large meaningful differences.
Time frame: Day 85
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had AQLQ(S) data at Day 85 (n=69, 63, 76, and 68 for placebo, 30, 100, and 300 mg MEDI-528, respectively).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis) | 53 Participants | 57.871 |
| MEDI528 30 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis) | 43 Participants | 60.584 |
| MEDI528 100 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis) | 52 Participants | 53.11 |
| MEDI528 300 mg | Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis) | 49 Participants | 55.339 |
Comparison: Combined MEDI-528 dose groups versus placebop-value: 0.208Fisher Exact
Secondary
Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528
Proportion of participants with detectable anti-drug antibodies to MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528 and placebo
Time frame: Days 1, 29, 57, 85, 127, 169, 176, 204,260, and 323
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo (n=82) group and received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528 | 4 Participants | — |
| MEDI528 30 mg | Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528 | 15 Participants | 1.53 |
| MEDI528 100 mg | Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528 | 4 Participants | 1.83 |
| MEDI528 300 mg | Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528 | 3 Participants | 1.99 |
Secondary
Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)
Time to first asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 176
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 5.3 |
| MEDI528 30 mg | Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 7.15 |
| MEDI528 100 mg | Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 4.7 |
| MEDI528 300 mg | Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 5.4 |
p-value: 0.717Log Rank
p-value: 0.07Log Rank
p-value: 0.934Log Rank
Secondary
Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)
Time to first asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 92
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 2.1 |
| MEDI528 30 mg | Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 3.38 |
| MEDI528 100 mg | Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 2.14 |
| MEDI528 300 mg | Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis) | NA Day | 95% Confidence Interval 2.27 |
p-value: 0.144Log Rank
p-value: 0.395Log Rank
p-value: 0.863Log Rank
Secondary
Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) \> or = 1.5 Through Day 176 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Days 1 - 176
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had ACQ data through Day 176.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis) | 15.0 Day | 95% Confidence Interval 4.07 |
| MEDI528 30 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis) | 17.0 Day | 95% Confidence Interval 4.57 |
| MEDI528 100 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis) | 20.0 Day | 95% Confidence Interval 3.63 |
| MEDI528 300 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis) | 20.0 Day | 95% Confidence Interval 4.7 |
p-value: 0.712Log Rank
p-value: 0.5086Log Rank
p-value: 0.5184Log Rank
Secondary
Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis)
Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) \> or = 0.5 through Day 92 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score ≥ 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Days 1 - 92
Population: All participants who were randomized into the 30 mg MEDI-528 (n=81), 100 mg MEDI-528 (n=83), 300 mg MEDI-528 (n=81), or placebo group (n=82) who had ACQ data through Day 92.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis) | 15.0 Day | 95% Confidence Interval 2.62 |
| MEDI528 30 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis) | 17.0 Day | 95% Confidence Interval 2.93 |
| MEDI528 100 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis) | 20.0 Day | 95% Confidence Interval 2.67 |
| MEDI528 300 mg | Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis) | 20.0 Day | 95% Confidence Interval 2.89 |
p-value: 0.7171Log Rank
p-value: 0.6219Log Rank
p-value: 0.6182Log Rank
Secondary
Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis)
Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 176
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis) | 0.58 Exacerbations per participant year | 95% Confidence Interval 0.96 |
| MEDI528 30 mg | Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis) | 0.64 Exacerbations per participant year | 95% Confidence Interval 1.15 |
| MEDI528 100 mg | Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis) | 0.28 Exacerbations per participant year | — |
| MEDI528 300 mg | Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis) | 0.58 Exacerbations per participant year | — |
p-value: 0.756Pairwise Poisson Regression
p-value: 0.047Pairwise Poisson Regression
p-value: 1Pairwise Poisson Regression
Secondary
Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis)
Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.
Time frame: Days 1 - 92
Population: All participants who were randomized and received at least one dose of investigational product (30, 100, or 300 mg MEDI-528 or placebo)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis) | 0.53 Exacerbations per participant year | 95% Confidence Interval 0.96 |
| MEDI528 30 mg | Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis) | 0.82 Exacerbations per participant year | 95% Confidence Interval 1.15 |
| MEDI528 100 mg | Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis) | 0.33 Exacerbations per participant year | — |
| MEDI528 300 mg | Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis) | 0.39 Exacerbations per participant year | — |
p-value: 0.271Pairwise Poisson Regression
p-value: 0.319Pairwise Poisson Regression
p-value: 0.502Pairwise Poisson Regression