Trial Outcomes & Findings for Efficacy and Safety of AQX-1125 in Unstable COPD (NCT NCT01954628)
NCT ID: NCT01954628
Last Updated: 2017-06-12
Results Overview
The primary variable (endpoint) of this study is the difference in the Area Above the Curve (AAC) for the daily EXACT score from baseline to Week 12 between subjects treated with AQX-1125 and placebo.The EXACT questionnaire is a patient reported outcome (PRO) measure designed to standardise the method for evaluating the frequency, severity and duration of acute exacerbations of COPD. The EXACT is a 14-item daily questionnaire where each item is assessed on a 5 or 6 point ordinal scale. Participants completed the EXACT questionnaire on a daily basis via an electronic diary from Day 1 (pre-dose) to Day 84 (week 12). Higher scores on the daily EXACT questionnaire indicate a more severe health state. When the post-treatment EXACT scores are lower (i.e. improved symptoms) than baseline EXACT, the AACs are positive.
COMPLETED
PHASE2
400 participants
12 weeks
2017-06-12
Participant Flow
The study was conducted in 8 countries: Australia, Denmark, Finland, Hungary, New Zealand, Poland, Sweden and US. US subjects participating in 6 month safety follow-up continued in the study until November 2015.
Four hundred subjects were randomized into two subsets: (1) Subjects suitable for outpatient treatment of a current exacerbation of COPD (within 3 days of diagnosis) \& (2) Subjects who had been hospitalized in order to treat their exacerbation for not more than 7 days \& were ready to be discharged or had been discharged within the last 3 days.
Participant milestones
| Measure |
AQX-1125 (200 mg)
AQX-1125 (200 mg capsule), oral once daily for 12 weeks. All standard of care treatments for COPD were permitted throughout the study with the exception of Roflumilast and Theophylline.
|
Placebo
Placebo (matching AQX-1125 capsule), oral, once daily for 12 weeks. Placebo control. All standard of care treatments for COPD were permitted throughout the study with the exception of Roflumilast and Theophylline.
|
|---|---|---|
|
Overall Study
STARTED
|
200
|
200
|
|
Overall Study
Full Analysis Set (FAS)
|
200
|
198
|
|
Overall Study
Safety Set
|
200
|
200
|
|
Overall Study
Pharmacokinetic Population
|
181
|
0
|
|
Overall Study
US 6 Month Ophthalmology Safety Visit
|
37
|
32
|
|
Overall Study
COMPLETED
|
169
|
173
|
|
Overall Study
NOT COMPLETED
|
31
|
27
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of AQX-1125 in Unstable COPD
Baseline characteristics by cohort
| Measure |
AQX-1125 (200 mg)
n=200 Participants
1 x AQX-1125 capsule daily
AQX-1125: Synthetic SHIP1 activator
|
Placebo
n=200 Participants
1 x Placebo capsule daily
Placebo: Placebo control
|
Total
n=400 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.8 years
STANDARD_DEVIATION 8.2 • n=99 Participants
|
64.4 years
STANDARD_DEVIATION 8.5 • n=107 Participants
|
65.1 years
STANDARD_DEVIATION 8.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=99 Participants
|
91 Participants
n=107 Participants
|
190 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=99 Participants
|
109 Participants
n=107 Participants
|
210 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
193 Participants
n=99 Participants
|
193 Participants
n=107 Participants
|
386 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
188 Participants
n=99 Participants
|
189 Participants
n=107 Participants
|
377 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
New Zealand
|
3 participants
n=99 Participants
|
3 participants
n=107 Participants
|
6 participants
n=206 Participants
|
|
Region of Enrollment
Sweden
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Region of Enrollment
Hungary
|
40 participants
n=99 Participants
|
43 participants
n=107 Participants
|
83 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
51 participants
n=99 Participants
|
53 participants
n=107 Participants
|
104 participants
n=206 Participants
|
|
Region of Enrollment
Finland
|
5 participants
n=99 Participants
|
3 participants
n=107 Participants
|
8 participants
n=206 Participants
|
|
Region of Enrollment
Denmark
|
13 participants
n=99 Participants
|
13 participants
n=107 Participants
|
26 participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
81 participants
n=99 Participants
|
75 participants
n=107 Participants
|
156 participants
n=206 Participants
|
|
Region of Enrollment
Australia
|
7 participants
n=99 Participants
|
9 participants
n=107 Participants
|
16 participants
n=206 Participants
|
|
Body Mass Index
|
28.1 kg/m2
STANDARD_DEVIATION 6.6 • n=99 Participants
|
27.2 kg/m2
STANDARD_DEVIATION 6.1 • n=107 Participants
|
27.6 kg/m2
STANDARD_DEVIATION 6.3 • n=206 Participants
|
|
Number of COPD Exacerbations in Last 18 months
|
3.1 number of exacerbations/18 months
STANDARD_DEVIATION 1.7 • n=99 Participants
|
3.0 number of exacerbations/18 months
STANDARD_DEVIATION 1.4 • n=107 Participants
|
3.1 number of exacerbations/18 months
STANDARD_DEVIATION 1.5 • n=206 Participants
|
|
Number of Previous Hospitalizations for COPD
|
1.1 number of previous hospitlizations
STANDARD_DEVIATION 3.0 • n=99 Participants
|
0.9 number of previous hospitlizations
STANDARD_DEVIATION 1.6 • n=107 Participants
|
1.0 number of previous hospitlizations
STANDARD_DEVIATION 2.4 • n=206 Participants
|
|
Years Since COPD Diagnosis
|
8.2 years
STANDARD_DEVIATION 5.7 • n=99 Participants
|
7.8 years
STANDARD_DEVIATION 5.9 • n=107 Participants
|
8.0 years
STANDARD_DEVIATION 5.8 • n=206 Participants
|
|
Smoking Status
Current Smokers
|
69 participants
n=99 Participants
|
103 participants
n=107 Participants
|
172 participants
n=206 Participants
|
|
Smoking Status
Former Smoker
|
131 participants
n=99 Participants
|
97 participants
n=107 Participants
|
228 participants
n=206 Participants
|
|
Smoking Pack Years
|
40.2 pYears
STANDARD_DEVIATION 22.0 • n=99 Participants
|
41.2 pYears
STANDARD_DEVIATION 20.9 • n=107 Participants
|
40.7 pYears
STANDARD_DEVIATION 21.4 • n=206 Participants
|
|
Nicotine Replacement Therapy Use
Yes
|
196 participants
n=99 Participants
|
195 participants
n=107 Participants
|
391 participants
n=206 Participants
|
|
Nicotine Replacement Therapy Use
No
|
4 participants
n=99 Participants
|
5 participants
n=107 Participants
|
9 participants
n=206 Participants
|
|
Post-bronchodilator FEV1/FVC Ratio
|
0.51 ratio
STANDARD_DEVIATION 0.11 • n=99 Participants
|
0.52 ratio
STANDARD_DEVIATION 0.11 • n=107 Participants
|
0.52 ratio
STANDARD_DEVIATION 0.11 • n=206 Participants
|
|
Post-bronchodilator FEV1% of Predicted
|
50.2 percent predicted
STANDARD_DEVIATION 13.9 • n=99 Participants
|
50.9 percent predicted
STANDARD_DEVIATION 13.2 • n=107 Participants
|
50.6 percent predicted
STANDARD_DEVIATION 13.5 • n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS). The FAS was all randomized subjects who have received at least one dose of the study drug and had at least one efficacy assessment (valid diary entries) post-baseline. Imputation, the mean of the last 5 days, counted backwards from day of last recording, in the treatment period will be used.
The primary variable (endpoint) of this study is the difference in the Area Above the Curve (AAC) for the daily EXACT score from baseline to Week 12 between subjects treated with AQX-1125 and placebo.The EXACT questionnaire is a patient reported outcome (PRO) measure designed to standardise the method for evaluating the frequency, severity and duration of acute exacerbations of COPD. The EXACT is a 14-item daily questionnaire where each item is assessed on a 5 or 6 point ordinal scale. Participants completed the EXACT questionnaire on a daily basis via an electronic diary from Day 1 (pre-dose) to Day 84 (week 12). Higher scores on the daily EXACT questionnaire indicate a more severe health state. When the post-treatment EXACT scores are lower (i.e. improved symptoms) than baseline EXACT, the AACs are positive.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=179 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=183 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period.
|
415.4 Area Above Curve on Daily Exact Score
Interval 290.7 to 540.1
|
391.7 Area Above Curve on Daily Exact Score
Interval 268.2 to 515.1
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set. Missing post-treatment data imputed using the last observation carried forward principle.
The secondary objective is to evaluate the treatment effect of once daily administrations of AQX-1125 compared to placebo over 12 weeks on the COPD Assessment Tool (CAT) score.The CAT questionnaire measures the impact of COPD on wellbeing and daily life. Participants answer 8 questions on a scale from 0 (best) to 5 (worst). The total score ranges from 0 to 40 with higher scores indicating more impact. A negative change from baseline indicates improvement. The change in total CAT score from Day 1, before taking study drug (baseline), to end of the 12 week treatment period was compared between the two treatments using an ANOVA model adjusting for treatment and region and including the baseline score as a covariate.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=179 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=182 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
Change From Baseline in COPD Assessment Tool (CAT) Score
|
-4.05 COPD Assessment Tool Score
Interval -5.06 to -3.04
|
-3.71 COPD Assessment Tool Score
Interval -4.71 to -2.71
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set was used and analyzed using the negative binomial regression model with fixed factors treatment, region and time in study as offset. Adjusted means for treatment group shows number of exacerbations/year.
The secondary objective is to evaluate the treatment effect of once daily administrations of AQX-1125 compared to placebo over 12 weeks on the number of COPD exacerbations (MTE). COPD exacerbations were referred to as Medically Treated Exacerbations (MTEs) and identified as a change in symptoms and/or signs of COPD requiring prescription of one or both of: (1) Course of oral corticosteroids or (2) Antibiotic(s).
Outcome measures
| Measure |
AQX-1125 (200mg)
n=200 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=198 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE))
|
1.776 Number of exacerbations/year
Interval 1.374 to 2.297
|
1.641 Number of exacerbations/year
Interval 1.261 to 2.135
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set
The secondary objective is to evaluate the treatment effect of once daily administrations of AQX-1125 compared to placebo over 12 weeks on the time to first exacerbation requiring medical intervention of oral corticosteroids and/or antibiotics.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=200 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=198 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
Time to First COPD Exacerbation
|
38.1 day(s)
Standard Deviation 21.3
|
43.9 day(s)
Standard Deviation 24.1
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set.
The number of subjects that presented with a COPD exacerbation during the 12 week treatment period.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=200 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=198 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
The Number of Subjects With at Least One COPD Exacerbation.
|
48 participants
|
51 participants
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full analysis set. Missing post-treatment data imputed using the last observation carried forward principle.
The secondary objective is to evaluate the treatment effect of once daily administrations of AQX-1125 compared to placebo over 12 weeks on forced expiratory volume in 1 second \[FEV1\]. FEV1 was determined from post-bronchodilator spirometry testing done at clinic visits.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=184 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=185 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
Change From Baseline in FEV1
|
-0.02 Liter
Interval -0.06 to 0.02
|
0.01 Liter
Interval -0.03 to 0.06
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: PK Population
The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma.
Outcome measures
| Measure |
AQX-1125 (200mg)
n=168 Participants
1 x AQX-1125 capsule daily
|
Placebo
n=163 Participants
1 x Placebo capsule daily
|
AQX-1125 Week 12
n=145 Participants
Week 12 PK Week 12 PK
|
|---|---|---|---|
|
AQX-1125 Concentrations in Plasma (Trough Values)
|
170.1 micrograms per Liter
Geometric Coefficient of Variation 70.5
|
163.9 micrograms per Liter
Geometric Coefficient of Variation 74.5
|
120.5 micrograms per Liter
Geometric Coefficient of Variation 80.0
|
Adverse Events
AQX-1125
Placebo
Serious adverse events
| Measure |
AQX-1125
n=200 participants at risk
1 x AQX-1125 capsule daily
AQX-1125: Synthetic SHIP1 activator
|
Placebo
n=200 participants at risk
1 x Placebo capsule daily
Placebo: Placebo control
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
0.50%
1/200 • Number of events 1 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
4.0%
8/200 • Number of events 9 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
|
Infections and infestations
Pneumonia
|
1.5%
3/200 • Number of events 3 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
1.0%
2/200 • Number of events 2 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
1.0%
2/200 • Number of events 2 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
1.0%
2/200 • Number of events 2 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
Other adverse events
| Measure |
AQX-1125
n=200 participants at risk
1 x AQX-1125 capsule daily
AQX-1125: Synthetic SHIP1 activator
|
Placebo
n=200 participants at risk
1 x Placebo capsule daily
Placebo: Placebo control
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.5%
11/200 • Number of events 13 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
4.5%
9/200 • Number of events 9 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
|
Nervous system disorders
Headache
|
6.0%
12/200 • Number of events 12 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
6.5%
13/200 • Number of events 14 • 12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in \>1 subjects per treatment arm.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators shall not publish any articles or make any presentations or communications (including any written, oral or electronic manuscript, abstract, presentation or other publication) relating to the Services, Sponsor Information, Study Drug or other Material, Deliverables or other Developments, in whole or part, without the prior written consent of the Sponsor.
- Publication restrictions are in place
Restriction type: OTHER