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The primary objective of this study is to evaluate the effect of 12 weeks of treatment with once daily administration of AQX-1125 compared to placebo in subjects following exacerbations of Chronic Obstructive Pulmonary Disease (COPD) by targeting the SHIP1 (Src Homology 2-containing Inositol-5'-Phosphatase 1) pathway.
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Acute exacerbations of COPD are usually treated with steroids and/or antibiotics. Currently this conventional therapy has significant side effects including osteoporosis, cataracts and suppression of the immune system (from the steroids) and increasing bacterial resistance and other side effects from the use of antibiotics. During an acute exacerbation of COPD, the inflammation in the airways increases.
AQX-1125 represents a new type drug that based current data is thought decrease the inflammatory process and therefore may provide a therapeutic benefit in the treatment of COPD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AQX-1125 | Experimental | 1 x AQX-1125 capsule daily |
|
| Placebo | Placebo Comparator | 1 x Placebo capsule daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AQX-1125 | Drug | Synthetic SHIP1 activator |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period. | 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. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in COPD Assessment Tool (CAT) Score | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen B Shrewsbury, MD | Aquinox Pharmaceuticals (Canada) Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Cincinnati | Cincinnati | Ohio | 45267 | United States | ||
| Department of Respiratory & Sleep Medicine, Westmead Hospital |
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| Label | URL |
|---|---|
| GOLD COPD Guidelines | View source |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety set.
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| ID | Title | Description |
|---|---|---|
| BG000 | AQX-1125 (200 mg) | 1 x AQX-1125 capsule daily AQX-1125: Synthetic SHIP1 activator |
| BG001 | Placebo | 1 x Placebo capsule daily Placebo: Placebo control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period. | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Area Above Curve on Daily Exact Score | 12 weeks |
12 weeks treatment; up to 6 months safety follow-up.
SAEs listed occurred in >1 subjects per treatment arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AQX-1125 | 1 x AQX-1125 capsule daily AQX-1125: Synthetic SHIP1 activator | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment | COPD exacerbations occurring during the study should not have been reported as SAEs (as per protocol). However, 10 events were reported (1 in AQX-1125 group and 9 in placebo). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
Secondary objective of "The frequency and severity of AEs and changes in physical exam, vital signs, ophthalmic exam, laboratory tests, weight, ECG, and con meds" was monitored throughout the study, clinically significant events were reported as AEs.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical | Aquinox Pharmaceuticals (Canada) Inc. | +1 (604) 629-9223 | clinical@aqxpharma.com |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C582990 | 4-(4-(aminomethyl)-7a-methyl-1-methylideneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexan-1-ol |
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| Drug |
Placebo control |
|
| 12 weeks |
| Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE)) | 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). | 12 weeks |
| Time to First COPD Exacerbation | 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. | 12 weeks |
| The Number of Subjects With at Least One COPD Exacerbation. | The number of subjects that presented with a COPD exacerbation during the 12 week treatment period. | 12 weeks |
| Change From Baseline in FEV1 | 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. | 12 weeks |
| AQX-1125 Concentrations in Plasma (Trough Values) | The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma. | 12 weeks |
| Wentworthville |
| New South Wales |
| 2145 |
| Australia |
| Department of Respiratory Medicine, Odense University Hospital | Odense | Denmark |
| Biomedicum Helsinki | Helsinki | Finland |
| Csongrád Megyei Melkasi Betegségek Szakkórháza | Deszk | Hungary |
| P3 Research | Wellington | New Zealand |
| Medical University of Lodz | Lodz | Poland |
| Lung and Allergy Clinic, Skåne University Hospital | Lund | Sweden |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m2 |
|
| Number of COPD Exacerbations in Last 18 months | Mean | Standard Deviation | number of exacerbations/18 months |
|
| Number of Previous Hospitalizations for COPD | Mean | Standard Deviation | number of previous hospitlizations |
|
| Years Since COPD Diagnosis | Mean | Standard Deviation | years |
|
| Smoking Status | Number | participants |
|
| Smoking Pack Years | Mean | Standard Deviation | pYears |
|
| Nicotine Replacement Therapy Use | Number | participants |
|
| Post-bronchodilator FEV1/FVC Ratio | Mean | Standard Deviation | ratio |
|
| Post-bronchodilator FEV1% of Predicted | Mean | Standard Deviation | percent predicted |
|
| ID | Title | Description |
|---|---|---|
| OG000 | AQX-1125 (200mg) | 1 x AQX-1125 capsule daily |
| OG001 | Placebo | 1 x Placebo capsule daily |
|
|
|
| Secondary | Change From Baseline in COPD Assessment Tool (CAT) Score | 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. | Full analysis set. Missing post-treatment data imputed using the last observation carried forward principle. | Posted | Least Squares Mean | 95% Confidence Interval | COPD Assessment Tool Score | 12 weeks |
|
|
|
|
| Secondary | Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE)) | 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Number of exacerbations/year | 12 weeks |
|
|
|
|
| Secondary | Time to First COPD Exacerbation | 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. | Full analysis set | Posted | Mean | Standard Deviation | day(s) | 12 weeks |
|
|
|
| Secondary | The Number of Subjects With at Least One COPD Exacerbation. | The number of subjects that presented with a COPD exacerbation during the 12 week treatment period. | Full analysis set. | Posted | Number | participants | 12 weeks |
|
|
|
| Secondary | Change From Baseline in FEV1 | 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. | Full analysis set. Missing post-treatment data imputed using the last observation carried forward principle. | Posted | Least Squares Mean | 95% Confidence Interval | Liter | 12 weeks |
|
|
|
|
| Secondary | AQX-1125 Concentrations in Plasma (Trough Values) | The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per Liter | 12 weeks |
|
|
|
| 200 |
| 6 |
| 200 |
| 21 |
| 200 |
| EG001 | Placebo | 1 x Placebo capsule daily Placebo: Placebo control | 1 | 200 | 12 | 200 | 21 | 200 |
|
| Pneumonia | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
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.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |