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

• ClinicalTrials.gov Identifier: NCT01954628
• Recruitment Status: Completed
• First Posted: October 7, 2013
• Results First Posted: June 12, 2017
• Last Update Posted: June 12, 2017
• Sponsor: Aquinox Pharmaceuticals (Canada) Inc.
• Information provided by (Responsible Party): Aquinox Pharmaceuticals (Canada) Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COPD	Drug: AQX-1125; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2013
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period. [ Time Frame: 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 :

1. Change From Baseline in COPD Assessment Tool (CAT) Score [ Time Frame: 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.
2. Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE)) [ Time Frame: 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).

3. Time to First COPD Exacerbation [ Time Frame: 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.
4. The Number of Subjects With at Least One COPD Exacerbation. [ Time Frame: 12 weeks ]
   The number of subjects that presented with a COPD exacerbation during the 12 week treatment period.
5. Change From Baseline in FEV1 [ Time Frame: 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.

6. AQX-1125 Concentrations in Plasma (Trough Values) [ Time Frame: 12 weeks ]
   The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

Australia, New South Wales

Department of Respiratory & Sleep Medicine, Westmead Hospital

Wentworthville, New South Wales, Australia, 2145

Denmark

Department of Respiratory Medicine, Odense University Hospital

Odense, Denmark

Finland

Biomedicum Helsinki

Helsinki, Finland

Hungary

Csongrád Megyei Melkasi Betegségek Szakkórháza

Deszk, Hungary

New Zealand

P3 Research

Wellington, New Zealand

Poland

Medical University of Lodz

Lodz, Poland

Sweden

Lung and Allergy Clinic, Skåne University Hospital

Lund, Sweden

Sponsors and Collaborators

Aquinox Pharmaceuticals (Canada) Inc.

Investigators

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

More Information

Additional Information:

GOLD COPD Guidelines 

• Responsible Party: Aquinox Pharmaceuticals (Canada) Inc.
• ClinicalTrials.gov Identifier: NCT01954628
• Other Study ID Numbers: AQX-1125-202
• First Posted: October 7, 2013
• Results First Posted: June 12, 2017
• Last Update Posted: June 12, 2017
• Last Verified: May 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Aquinox Pharmaceuticals (Canada) Inc.:

Exacerbation of COPD; Unstable COPD

Additional relevant MeSH terms:

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases