Efficacy and Safety of AQX-1125 in Unstable COPD

Phase 2

Completed

• Conditions: COPD
• Interventions: Drug: Placebo; Drug: AQX-1125

• Registration Number: NCT01954628
• Lead Sponsor: Aquinox Pharmaceuticals (Canada) Inc.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2013-09-21
• Study First Submitted QC: 2013-09-27
• Study Start: 2013-10
• Study First Posted: 2013-10-07
• Primary Completion: 2015-07
• Study Completion: 2015-12
• Status Verified: 2017-05
• Results First Submitted: 2017-05-08
• Results First Submitted QC: 2017-05-08
• Last Update Submitted: 2017-05-08
• Results First Posted: 2017-06-12
• Last Update Posted: 2017-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Male or female aged ≥40 years at screening
2. History of COPD for at least 18 months prior to screening, characterised by excessive sputum production
3. Chronic productive cough for at least 3 months in each of the 2 years prior to screening (if other causes of productive cough have been excluded) and/or an exacerbation of COPD with predominantly bronchitic symptoms at enrolment
4. At least 2 documented exacerbations during the last 18 months prior to screening.
5. Presentation of a diagnosed acute exacerbation of COPD, or have recently (within 3 days) been discharged from hospital due to an acute exacerbation of COPD
6. Ability to perform pulmonary function testing and with documented fixed airway obstruction determined by an FEV1 /FVC [forced vital capacity] ratio (post-bronchodilator) of <0.70 and a predicted FEV1 value of 30%-80% of normal within the 6 months prior to Visit 1.
7. Former smoker or current smoker, both with a smoking history of at least 10 pack years

Exclusion Criteria

1. Diagnosis of other relevant lung disease (e.g. asthma, cystic fibrosis [CF] or significant non-CF bronchiectasis)
2. Known alpha-1-antitrypsin deficiency
3. Treatment with roflumilast or theophylline within 1 month prior to screening
4. Lobar pneumonia, with current positive chest X-ray (CXR) or within the 3 months prior to screening including the presence of any new radiological infiltrate on CXR within the previous two weeks
5. Hospitalisation for more than 7 days for current acute exacerbation, or the requirement for intubation during hospitalisation
6. For outpatients, prior medical history indicating that previous exacerbations required >3 weeks to stabilise

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	1 x Placebo capsule daily
AQX-1125	AQX-1125	1 x AQX-1125 capsule daily

Primary Outcome Measures

Name	Time	Method
The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period.	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in COPD Assessment Tool (CAT) Score	12 weeks	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.
Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE))	12 weeks	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).
Time to First COPD Exacerbation	12 weeks	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.
The Number of Subjects With at Least One COPD Exacerbation.	12 weeks	The number of subjects that presented with a COPD exacerbation during the 12 week treatment period.
Change From Baseline in FEV1	12 weeks	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.
AQX-1125 Concentrations in Plasma (Trough Values)	12 weeks	The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma.

Trial Locations

Locations (8)

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Csongrád Megyei Melkasi Betegségek Szakkórháza; 🇭🇺 Deszk, Hungary

Department of Respiratory & Sleep Medicine, Westmead Hospital; 🇦🇺 Wentworthville, New South Wales, Australia

Department of Respiratory Medicine, Odense University Hospital; 🇩🇰 Odense, Denmark

Biomedicum Helsinki; 🇫🇮 Helsinki, Finland

Medical University of Lodz; 🇵🇱 Lodz, Poland

P3 Research; 🇳🇿 Wellington, New Zealand

Lung and Allergy Clinic, Skåne University Hospital; 🇸🇪 Lund, Sweden