COPDPhase 2FLAGSHIPNCT01954628
Efficacy and Safety of AQX-1125 in Unstable COPD
A Phase 2 study testing AQX-1125 in people with COPD, run by Aquinox Pharmaceuticals (Canada) Inc. at 8 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD
- What is being tested?
- AQX-1125
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 8 sitesin 8 countries
- Study dates
- Oct 2013to Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥40 years at screening
- History of COPD for at least 18 months prior to screening, characterised by excessive sputum production
- 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
- At least 2 documented exacerbations during the last 18 months prior to screening.
- 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
- 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.
- Former smoker or current smoker, both with a smoking history of at least 10 pack years
Who cannot join
- Diagnosis of other relevant lung disease (e.g. asthma, cystic fibrosis [CF] or significant non-CF bronchiectasis)
- Known alpha-1-antitrypsin deficiency
- Treatment with roflumilast or theophylline within 1 month prior to screening
- 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
- Hospitalisation for more than 7 days for current acute exacerbation, or the requirement for intubation during hospitalisation
- For outpatients, prior medical history indicating that previous exacerbations required >3 weeks to stabilise
Trial locations and contacts
8 sites in 8 countries.
8 sites in 8 countries
Australia1 site
Department of Respiratory & Sleep Medicine, Westmead Hospital
Wentworthville, New South Wales, 2145
Denmark1 site
Department of Respiratory Medicine, Odense University Hospital
Odense
About this study
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
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.
Read the 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.
- Conditions
- COPD
- Being tested
- AQX-1125, Placebo
- Keywords
- Exacerbation of COPD, Unstable COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AQX-1125Drug
Synthetic SHIP1 activator
PlaceboDrug
Placebo control
| Study group | Role | What they receive |
|---|---|---|
| AQX-1125 | Experimental | 1 x AQX-1125 capsule daily Receives: Drug: AQX-1125 |
| Placebo | Placebo comparator | 1 x Placebo capsule daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (6)
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 weeks
AQX-1125 Concentrations in Plasma (Trough Values)
The secondary objectives are to evaluate the pharmacokinetics (PK) of AQX-1125 in plasma.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aquinox Pharmaceuticals (Canada) Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen B Shrewsbury, MD, Study director, Aquinox Pharmaceuticals (Canada) Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01954628
- Sponsor's protocol ID
- AQX-1125-202
- Acronym
- FLAGSHIP
- Status last verified
- May 2017
- First submitted
- 21 Sep 2013
- Last updated
- 12 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01954628
- Acronym / sponsor ID
- FLAGSHIP / AQX-1125-202
- Conditions
- COPD
- Keywords
- Exacerbation of COPD, Unstable COPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Aquinox Pharmaceuticals (Canada) Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 7 Oct 2013 (estimated)
- Results
- Posted 12 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AQX-1125 | Experimental | Drug: AQX-11251 x AQX-1125 capsule daily |
| Placebo | Placebo comparator | Drug: Placebo1 x Placebo capsule daily |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female aged ≥40 years at screening
- History of COPD for at least 18 months prior to screening, characterised by excessive sputum production
- 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
- At least 2 documented exacerbations during the last 18 months prior to screening.
- 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
Key exclusion criteria (6 listed)
- Diagnosis of other relevant lung disease (e.g. asthma, cystic fibrosis [CF] or significant non-CF bronchiectasis)
- Known alpha-1-antitrypsin deficiency
- Treatment with roflumilast or theophylline within 1 month prior to screening
- 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
- Hospitalisation for more than 7 days for current acute exacerbation, or the requirement for intubation during hospitalisation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AQX-1125Synthetic SHIP1 activator | Drug | AQX-1125 |
| PlaceboPlacebo control | Drug | Placebo |
Primary outcome
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.
6 secondary outcomes
Change From Baseline in COPD Assessment Tool (CAT) Score
Time frame: 12 weeks
Analysis of the Number of COPD Exacerbations (Medically Treated Event (MTE))
Time frame: 12 weeks
Time to First COPD Exacerbation
Time frame: 12 weeks
The Number of Subjects With at Least One COPD Exacerbation.
Time frame: 12 weeks
Change From Baseline in FEV1
Time frame: 12 weeks
AQX-1125 Concentrations in Plasma (Trough Values)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- GOLD COPD GuidelinesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen B Shrewsbury, MD study director
Aquinox Pharmaceuticals (Canada) Inc.
8 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AQX-1125 in people with COPD, run by Aquinox Pharmaceuticals (Canada) Inc. at 8 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia, Denmark, Finland, Hungary and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Primary Efficacy Variable Was the AAC for Daily EXACT Scores During the 12-week Treatment Period. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2017.