Efficacy and Safety of AQX-1125 in Unstable COPD (FLAGSHIP)

The FLAGSHIP Study: A 12-week Phase II Study to Evaluate the Efficacy and Safety of AQX-1125 Following Exacerbations in Patients With Chronic Obstructive Pulmonary Disease (COPD) by Targeting the SHIP1 Pathway

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo; Drug: AQX-1125

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 Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wentworthville, New South Wales, Australia, 2145
      • Department of Respiratory & Sleep Medicine, Westmead Hospital
• Denmark
  • Odense, Denmark
    • Department of Respiratory Medicine, Odense University Hospital
• Finland
  • Helsinki, Finland
    • Biomedicum Helsinki
• Hungary
  • Deszk, Hungary
    • Csongrád Megyei Melkasi Betegségek Szakkórháza
• New Zealand
  • Wellington, New Zealand
    • P3 Research
• Poland
  • Lodz, Poland
    • Medical University of Lodz
• Sweden
  • Lund, Sweden
    • Lung and Allergy Clinic, Skåne University Hospital
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AQX-1125; 1 x AQX-1125 capsule daily	Drug: AQX-1125; Synthetic SHIP1 activator
Placebo Comparator: Placebo; 1 x Placebo capsule daily	Drug: Placebo; Placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Aquinox Pharmaceuticals (Canada) Inc.
• Investigators: Study Director: Stephen B Shrewsbury, MD, Aquinox Pharmaceuticals (Canada) Inc.

Publications and helpful links

Helpful Links

• GOLD COPD Guidelines

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 21, 2013
• First Submitted That Met QC Criteria: September 27, 2013
• First Posted (Estimate): October 7, 2013

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Exacerbation of COPD; Unstable COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AQX-1125-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO