A Study to Evaluate the Dosing of AMG 827 for Subjects With Inadequately Controlled Asthma

Study Overview
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Brief Summary
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The purpose of this study is to determine if AMG 827 is effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Determine the Safety and Efficacy of AMG 827 in Subjects With Inadequately Controlled Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: AMG 827
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women 18 to 65 years of age Percent of predicted FEV1 ≥ 50% and ≤ 80% At least 12% reversibility over pre-bronchodilator FEV1 Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000 µg/day fluticasone powder or equivalent Ongoing asthma symptoms with ACQ composite score ≥ 1.5 points Exclusion Criteria: Respiratory infection within 4 weeks of screening visit or 1 week of baseline visit History of chronic obstructive pulmonary disease or other chronic pulmonary condition other than asthma Any uncontrolled or clinically significant systemic disease (eg, uncontrolled diabetes, liver disease)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive the matching placebo administered as subcutaneous (SC) injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | Drug: Placebo<br>* SC injection.<br>|
| Experimental: AMG 827 140 mg<br>Participants will receive AMG 140 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | Drug: AMG 827<br>* SC injection.<br>|
| Experimental: AMG 827 210 mg<br>Participants will receive AMG 210 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | Drug: AMG 827<br>* SC injection.<br>|
| Experimental: AMG 827 280 mg<br>Participants will receive AMG 280 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | Drug: AMG 827<br>* SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | The ACQ is an instrument used in clinical research and practice to evaluate asthma control/impairment. It is a validated composite score that assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon awakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and forced expiratory volume in 1 second (FEV1). The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/limitation) scale. The total score is obtained by adding the value from each question and dividing by the number of questions. Higher scores indicates worsening of condition and a negative change from baseline indicates improvement. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FEV1 was performed both pre and post-administration of bronchodilator treatment at Baseline and Week 12. | Baseline and Week 12 | 
| Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 |  | Baseline and Week 12 | 
| Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | Participants recorded SABA use for 1 week prior to randomization (baseline) and the average number of days recorded was subtracted from average days of SABA use across 12 week intervention period. | Baseline to Week 12 | 
| Change From Baseline in Daily Asthma Symptom Score to Week 12 | Participants recorded their daily asthma symptoms in their electronic diaries (Ediary). It included 7 questions: frequency of night time awakening, time awake at night, wheezing, shortness of breath, cough, chest tightness and activity limitation. Daily asthma symptoms score is the sum of 7 individual scores (with the total score ranging from 0-21). Higher scores indicates worsening of condition and a negative change from baseline indicates improvement. | Baseline and Week 12 | 
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | The AQLQ is the most commonly used asthma specific instrument and includes evaluations of both symptom and quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms (Mitchell EA et al, 1997, Juniper et al, 1994, Christie MJ et al, 1993, Juniper et al, 1993). Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score = mean of the responses to the 32 questions. Higher scores indicate better quality of life and a positive change from baseline indicates improved symptoms. | Baseline and Week 12 | 
| Proportion of Asthma Symptom-free Days | Asthma symptom-free days were defined as a participant having a score of zero in their daily asthma symptom score. Asthma symptom-free days without SABA use were defined as a participant having a score of zero in their daily asthma symptom score and no SABA use. The proportion of asthma symptom-free days was calculated as the number of asthma symptom-free days over the number of days in the double-blind treatment period (12 weeks). | Up to Week 12 | 
| Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 |  | Week 8 (days 60 and 64), and pre-dose on Week 10 | 
| Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 |  | Week 8 (days 60 and 64), and pre-dose on Week 10 | 
| Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 |  | Week 8 (days 60 and 64), and pre-dose on Week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen, chronic inflammatory disease, wheezing