Trial Outcomes & Findings for Efficacy and Safety of QGE031versus Placebo and Omalizumab in Patients Aged 18-75 Years With Asthma (NCT NCT01716754)
NCT ID: NCT01716754
Last Updated: 2017-08-11
Results Overview
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.
COMPLETED
PHASE2
471 participants
Week 16
2017-08-11
Participant Flow
A total of 471 participants were randomized to one of the 14 treatment groups. Of these, 5 participants did not receive study treatment. Therefore, the full analysis set (FAS) and safety set included 466 participants.
The treatment arms for QGE031 and placebo were pooled into high dose QGE031 (240 mg q2w, 240 mg q4w, 180 mg q2w and 120 q2w), low dose QGE031 (36 mg q2w and 18 mg 2qw) and Placebo Total (all QGE031 placebo and Omalizumab placebo arms).
Participant milestones
| Measure |
QGE031 High Dose
Participants received QGE031 240 mg q2w, 240 mg q4w, 180 mg q2w or 120 mg q2w.
|
QGE031 Low Dose
Participants received QGE031 36 mg q2w or 18 mg q2w.
|
Omalizumab
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
Placebo Total
Participants received matching placebo to QGE031 or Omalizumab.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
199
|
40
|
135
|
97
|
|
Overall Study
FAS
|
199
|
40
|
131
|
96
|
|
Overall Study
Safety Set
|
199
|
40
|
131
|
96
|
|
Overall Study
COMPLETED
|
188
|
36
|
121
|
89
|
|
Overall Study
NOT COMPLETED
|
11
|
4
|
14
|
8
|
Reasons for withdrawal
| Measure |
QGE031 High Dose
Participants received QGE031 240 mg q2w, 240 mg q4w, 180 mg q2w or 120 mg q2w.
|
QGE031 Low Dose
Participants received QGE031 36 mg q2w or 18 mg q2w.
|
Omalizumab
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
Placebo Total
Participants received matching placebo to QGE031 or Omalizumab.
|
|---|---|---|---|---|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
|
Overall Study
Protocol deviation
|
0
|
2
|
7
|
2
|
|
Overall Study
Non-compliance with study treatment
|
0
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
4
|
2
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
0
|
4
|
3
|
Baseline Characteristics
Efficacy and Safety of QGE031versus Placebo and Omalizumab in Patients Aged 18-75 Years With Asthma
Baseline characteristics by cohort
| Measure |
QGE031 High Dose
n=199 Participants
Participants received QGE031 240 mg q2w, 240 mg q4w, 180 mg q2w or 120 mg q2w.
|
QGE031 Low Dose
n=40 Participants
Participants received QGE031 36 mg q2w or 18 mg q2w.
|
Omalizumab
n=135 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
Placebo Total
n=97 Participants
Participants received matching placebo to QGE031 or Omalizumab.
|
Total
n=471 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
47.6 Years
STANDARD_DEVIATION 13.86 • n=5 Participants
|
46.0 Years
STANDARD_DEVIATION 12.38 • n=7 Participants
|
46.8 Years
STANDARD_DEVIATION 13.35 • n=5 Participants
|
48.6 Years
STANDARD_DEVIATION 12.80 • n=4 Participants
|
47.4 Years
STANDARD_DEVIATION 13.36 • n=21 Participants
|
|
Sex: Female, Male
Female
|
113 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
288 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
183 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Week 16Population: The full analysis set (FAS) for the QGE031 240 mg q2w, placebo to QGE031 240 mg q2w and Omalizumab groups (n=120,49,131) was considered for the analysis. Only participants who had week 16 values were analyzed. The FAS included randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
QGE031 240 mg q2w
n=114 Participants
Participants received QGE031 240 mg q2w.
|
Placebo to QGE031 240 mg q2w
n=49 Participants
Participants received placebo to QGE031 240 mg q2w
|
Omalizumab
n=131 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
|---|---|---|---|
|
Percentage of QGE031 Participants With Clinically Important Improvement of <= -0.5 in the Asthma Control Questionnaire 7 (ACQ-7) Score Compared to Placebo
|
63.16 Percentage of participants
|
70.21 Percentage of participants
|
69.17 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 16 and 28Population: The FAS for the QGE031 240 mg q2w, placebo to QGE031 240 mg q2w and Omalizumab groups (n=120,49,131) was considered for the analysis. Participants who had values at both baseline and the post baseline time point were analyzed for that post baseline time point. The FAS included randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
QGE031 240 mg q2w
n=120 Participants
Participants received QGE031 240 mg q2w.
|
Placebo to QGE031 240 mg q2w
n=49 Participants
Participants received placebo to QGE031 240 mg q2w
|
Omalizumab
n=131 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
|---|---|---|---|
|
Change From Baseline in ACQ-7 Score
Week 4 (n=115,46,122)
|
-0.51 Score on a scale
Standard Deviation 0.709
|
-0.48 Score on a scale
Standard Deviation 0.834
|
-0.60 Score on a scale
Standard Deviation 0.705
|
|
Change From Baseline in ACQ-7 Score
Week 8 (n=110,46,122)
|
-0.68 Score on a scale
Standard Deviation 0.678
|
-0.62 Score on a scale
Standard Deviation 0.735
|
-0.78 Score on a scale
Standard Deviation 0.687
|
|
Change From Baseline in ACQ-7 Score
Week 12 (n=110,46,118)
|
-0.78 Score on a scale
Standard Deviation 0.738
|
-0.71 Score on a scale
Standard Deviation 0.724
|
-0.83 Score on a scale
Standard Deviation 0.737
|
|
Change From Baseline in ACQ-7 Score
Week 16 (n=114,48,120)
|
-0.75 Score on a scale
Standard Deviation 0.817
|
-0.79 Score on a scale
Standard Deviation 0.733
|
-0.89 Score on a scale
Standard Deviation 0.734
|
|
Change From Baseline in ACQ-7 Score
Week 28 (n112,47,115)
|
-0.62 Score on a scale
Standard Deviation 0.810
|
-0.63 Score on a scale
Standard Deviation 0.744
|
-0.59 Score on a scale
Standard Deviation 0.842
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set (FAS) for the QGE031 240 mg q2w, placebo to QGE031 240 mg q2w and Omalizumab groups (n=120,49,131) was considered for the analysis. Only participants who had week 16 values were analyzed. The FAS included randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
QGE031 240 mg q2w
n=114 Participants
Participants received QGE031 240 mg q2w.
|
Placebo to QGE031 240 mg q2w
n=47 Participants
Participants received placebo to QGE031 240 mg q2w
|
Omalizumab
n=120 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
|---|---|---|---|
|
Percentage of Participants With a Change From Baseline in ACQ-7 Score Less Than -1.1
|
40.35 Percentage of participants
|
34.04 Percentage of participants
|
36.67 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 16, Week 28Population: The FAS for the QGE031 240 mg q2w, placebo to QGE031 240 mg q2w and Omalizumab groups (n=120,49,131) was considered for the analysis. Participants who had values at both baseline and the post baseline time point were analyzed for that post baseline time point. The FAS included randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
QGE031 240 mg q2w
n=114 Participants
Participants received QGE031 240 mg q2w.
|
Placebo to QGE031 240 mg q2w
n=48 Participants
Participants received placebo to QGE031 240 mg q2w
|
Omalizumab
n=122 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
|---|---|---|---|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score
Week 16 (n=114,48,122)
|
0.53 Score on a scale
Standard Deviation 0.878
|
0.66 Score on a scale
Standard Deviation 0.624
|
0.79 Score on a scale
Standard Deviation 0.853
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score
Week 28 (n=114,47,121)
|
0.44 Score on a scale
Standard Deviation 0.899
|
0.63 Score on a scale
Standard Deviation 0.826
|
0.48 Score on a scale
Standard Deviation 0.871
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: The full analysis set (FAS) for the QGE031 240 mg q2w, placebo to QGE031 240 mg q2w and Omalizumab groups (n=120,49,131) was considered for the analysis. Only participants who had both baseline and week 16 values were analyzed. The FAS included randomized participants who received at least one dose of study drug.
Participants recorded their use of rescue medication into an electronic diary (eDiary). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
QGE031 240 mg q2w
n=117 Participants
Participants received QGE031 240 mg q2w.
|
Placebo to QGE031 240 mg q2w
n=48 Participants
Participants received placebo to QGE031 240 mg q2w
|
Omalizumab
n=122 Participants
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
|---|---|---|---|
|
Change From Baseline in Mean Number of Puffs of Morning, Evening and Total Daily Asthma Rescue Medication
Evening
|
-0.31 Number of puffs
Standard Error 0.082
|
-0.33 Number of puffs
Standard Error 0.126
|
-0.33 Number of puffs
Standard Error 0.084
|
|
Change From Baseline in Mean Number of Puffs of Morning, Evening and Total Daily Asthma Rescue Medication
Overall
|
-0.56 Number of puffs
Standard Error 0.145
|
-0.64 Number of puffs
Standard Error 0.226
|
-0.73 Number of puffs
Standard Error 0.148
|
|
Change From Baseline in Mean Number of Puffs of Morning, Evening and Total Daily Asthma Rescue Medication
Morning
|
-0.28 Number of puffs
Standard Error 0.072
|
-0.34 Number of puffs
Standard Error 0.113
|
-0.39 Number of puffs
Standard Error 0.073
|
Adverse Events
QGE031 High Dose
QGE031 Low Dose
Omalizumab
Placebo Total
Serious adverse events
| Measure |
QGE031 High Dose
n=199 participants at risk
Participants received QGE031 240 mg q2w, 240 mg q4w, 180 mg q2w or 120 mg q2w.
|
QGE031 Low Dose
n=40 participants at risk
Participants received QGE031 36 mg q2w or 18 mg q2w.
|
Omalizumab
n=131 participants at risk
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
Placebo Total
n=96 participants at risk
Participants received matching placebo to QGE031 or Omalizumab
|
|---|---|---|---|---|
|
Infections and infestations
Impetigo
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Infections and infestations
Influenza
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Infections and infestations
Pneumonia
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/199
|
0.00%
0/40
|
0.76%
1/131
|
0.00%
0/96
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Vaginal laceration
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
Cardiac disorders
Coronary artery disease
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/199
|
2.5%
1/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Immune system disorders
Drug hypersensitivity
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
Infections and infestations
Cellulitis
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Investigations
Alanine aminotransferase increased
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Investigations
Aspartate aminotransferase increased
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.50%
1/199
|
0.00%
0/40
|
0.76%
1/131
|
0.00%
0/96
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.50%
1/199
|
0.00%
0/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/199
|
0.00%
0/40
|
0.76%
1/131
|
0.00%
0/96
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/199
|
2.5%
1/40
|
0.00%
0/131
|
0.00%
0/96
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.50%
1/199
|
2.5%
1/40
|
0.00%
0/131
|
2.1%
2/96
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal dysplasia
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/199
|
0.00%
0/40
|
0.00%
0/131
|
1.0%
1/96
|
Other adverse events
| Measure |
QGE031 High Dose
n=199 participants at risk
Participants received QGE031 240 mg q2w, 240 mg q4w, 180 mg q2w or 120 mg q2w.
|
QGE031 Low Dose
n=40 participants at risk
Participants received QGE031 36 mg q2w or 18 mg q2w.
|
Omalizumab
n=131 participants at risk
Participants received omalizumab as per locally approved dosing table q2w or q4w.
|
Placebo Total
n=96 participants at risk
Participants received matching placebo to QGE031 or Omalizumab
|
|---|---|---|---|---|
|
General disorders
Injection site reaction
|
28.6%
57/199
|
12.5%
5/40
|
14.5%
19/131
|
5.2%
5/96
|
|
Infections and infestations
Nasopharyngitis
|
8.0%
16/199
|
5.0%
2/40
|
6.9%
9/131
|
9.4%
9/96
|
|
Infections and infestations
Viral upper respiratory tract infection
|
3.0%
6/199
|
5.0%
2/40
|
1.5%
2/131
|
6.2%
6/96
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
22.1%
44/199
|
32.5%
13/40
|
14.5%
19/131
|
28.1%
27/96
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER