Clinical trial NCT01954628: Efficacy and Safety of AQX-1125 in Unstable COPD
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: Exacerbation of COPD
Unstable COPD
Lead sponsor: Aquinox Pharmaceuticals (Canada) Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-07
Enrollment: 400
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period.
timeFrame: 12 weeks
Secondary outcomes:
measure: Change From Baseline in COPD Assessment Tool (CAT) Score
timeFrame: 12 weeks
measure: Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE))
timeFrame: 12 weeks
measure: Time to First COPD Exacerbation
timeFrame: 12 weeks
measure: The Number of Subjects With at Least One COPD Exacerbation.
timeFrame: 12 weeks
measure: Change From Baseline in FEV1
timeFrame: 12 weeks
measure: AQX-1125 Concentrations in Plasma (Trough Values)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Wentworthville
country: Australia
facility: Department of Respiratory & Sleep Medicine, Westmead Hospital
state: New South Wales
city: Odense
country: Denmark
facility: Department of Respiratory Medicine, Odense University Hospital
city: Helsinki
country: Finland
facility: Biomedicum Helsinki
city: Deszk
country: Hungary
facility: Csongrád Megyei Melkasi Betegségek Szakkórháza
city: Wellington
country: New Zealand
facility: P3 Research
city: Lodz
country: Poland
facility: Medical University of Lodz
city: Lund
country: Sweden
facility: Lung and Allergy Clinic, Skåne University Hospital
Study officials:
affiliation: Aquinox Pharmaceuticals (Canada) Inc.
name: Stephen B Shrewsbury, MD
role: STUDY_DIRECTOR
References: