Efficacy and Safety of QGE031versus Placebo and Omalizumab in Patients Aged 18-75 Years With Asthma

Study Overview
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Brief Summary
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This study assessed the effect on asthma control of different dose levels and regimens of QGE031 in asthma patients that are inadequately controlled with inhaled steroid and beta-2 agonist medication. Safety was assessed also. Comparison was to placebo and omalizumab. Information from this study was planned to support the design of future studies.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo and Active-controlled Study With Exploratory Dose-ranging to Investigate the Efficacy and Safety of 16 Weeks Treatment With Subcutaneous (s.c.) QGE031 in Asthma Patients Not Adequately Controlled With High-dose Inhaled Corticosteroids and Long Acting β2-agonists

Conditions
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Asthma

Intervention / Treatment
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* Drug: QGE031
* Drug: Omalizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A diagnosis of allergic asthma , uncontrolled on current medication. History of at least 1 asthma exacerbation during the last 1 year Forced Expiratory Volume in one second (FEV1) of ≥ 40% and ≤ 80% of the predicted normal value; reversibility following administration of bronchodilator must also be demonstrated (historical positive reversibility or bronchoprovocation result can be used). Key Exclusion Criteria: Baseline IgE levels or body weight outside the omalizumab dosing table. Use of tobacco products within the previous 6 months (Social occasional smokers may be included). Recent asthma attack/exacerbation or asthma worsening/ respiratory infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: QGE031 240 mg every 2 weeks (q2w)<br>Participants received QGE031 240 mg subcutaneously (s.c.) q2w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Experimental: QGE031 240 mg q4w<br>Participants received QGE031 240 mg s.c. q4w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Experimental: QGE031 180 mg q2w<br>Participants received QGE031 180 mg s.c. q2w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Experimental: QGE031 120 mg q2w<br>Participants received QGE031 120 mg s.c. q2w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Experimental: QGE031 36 mg q2w<br>Participants received QGE031 36 mg s.c. q2w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Experimental: QGE031 12 mg q2w<br>Participants received QGE031 12 mg s.c. q2w for 16 weeks. | Drug: QGE031<br>* QGE031 was supplied as 120 mg liquid in vial per 1 mL<br>|
| Active Comparator: Omalizumab (as per locally approved dosing table)<br>Participants received omalizumab as per locally approved dosing table s.c. q2w or q4w for 16 weeks. | Drug: Omalizumab<br>* Omalizumab was supplied as 150 mg lyophilisate in vial<br>* Other names: Xolair;|
| Placebo Comparator: Placebo to QGE031 240 mg q2w<br>Participants received matching placebo to QGE031 240 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to QGE031 240 mg q4w<br>Participants received placebo to QGE031 240 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to QGE031 180 mg q2w<br>Participants received QGE031 180 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to QGE031 120 mg q2w<br>Participants received QGE031 120 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to QGE031 36 mg q2w<br>Participants received QGE031 36 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to QGE031 12 mg q2w<br>Participants received QGE031 12 mg s.c. q2w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|
| Placebo Comparator: Placebo to omalizumab<br>Participants received placebo to omalizumab s.c. q2w or q4w for 16 weeks. | Drug: Placebo<br>* Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of QGE031 Participants With Clinically Important Improvement of <= -0.5 in the Asthma Control Questionnaire 7 (ACQ-7) Score Compared to Placebo | The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in ACQ-7 Score | The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7. A negative change from baseline indicates improvement. | Baseline, Weeks 4, 8, 12, 16 and 28 | 
| Percentage of Participants With a Change From Baseline in ACQ-7 Score Less Than -1.1 | The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7. | Week 16 | 
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to participants with asthma. The 32 items in the AQLQ were divided into four domain-specific scores and a total score as follows: Activity limitations = Mean of Items 1, 2, 3, 4, 5, 11, 19, 25, 28, 31, 32 (11 items); Symptoms = Mean of Items 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 29, 30 (12 items); Emotional function = Mean of Items 7, 13, 15, 21, 27 (5 items); Environmental stimuli = Mean of Items 9, 17, 23, 26 (4 items); and Overall Score = Mean of Items 1 to 32 (32 items). Each item of the AQLQ was equally weighted and scored along a 7-point scale, where 1 indicates maximal impairment and 7 indicates no impairment. Thus, higher scores indicate better asthma-related quality of life. The mean overall score ranged from 1 to 7. A positive change from baseline indicates improvement. | Baseline, Week 16, Week 28 | 
| Change From Baseline in Mean Number of Puffs of Morning, Evening and Total Daily Asthma Rescue Medication | Participants recorded their use of rescue medication into an electronic diary (eDiary). A negative change from baseline indicates improvement. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, asthma control, allergy, atopic, IgE, double-blind, placebo, omalizumab