A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults

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.

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.

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.

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.

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 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 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 (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 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 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.

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.

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.

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.

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

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.

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 in subjects receiving 30, 100, or 300 mg MEDI-528 and placebo

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.

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 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 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.