Chronic Obstructive Pulmonary DiseasePhase 2NCT03810183
A Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia
A Phase 2 study testing QAW039 in people with Chronic Obstructive Pulmonary Disease, run by Novartis Pharmaceuticals at 4 sites in 2 countries.
Trial summary
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in chronic obstructive pulmonary disease (COPD) patients with eosinophilia. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- QAW039
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 21 May 2019to 16 Jan 2020
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acceptable and reproducible spirometry with post-bronchodilator FEV1/FVC < 0.7 and post-bronchodilator FEV1≥ 30 and ≤ 80% of predicted at the screening and baseline visits (GOLD stage II or III COPD).
- Patients with a physician-diagnosed history of COPD for at least 1 year prior to screening visit, and a documented history of at least one COPD exacerbation within the year prior to screening visit and on a stable therapy regimen for COPD for at least 4 weeks prior to screening visit with inhaled glucocorticoid + one or more long acting bronchodilator.
- Current or ex-smokers who have a smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, or equivalent).
- Circulating eosinophils ≥ 300 cells/µL blood AND sputum eosinophils ≥ 3% of total cell count during screening period.
Who cannot join
- Patients with a past or current medical history of asthma.
- Patients with a past or current medical history of conditions other than COPD or allergic rhinitis that could result in elevated sputum eosinophils (e.g., asthma, hypereosinophilic syndrome, Churg-Strauss Syndrome). Patients with known parasitic infestation within 6 months prior to screening are also excluded.
- Patients who have had a respiratory tract infection or COPD worsening or systemic steroid use within 4 weeks prior to screening visit or between screening and randomization visits.
- Patients with history of concomitant chronic or severe pulmonary disease (e.g., sarcoidosis, interstitial lung disease, cystic fibrosis, tuberculosis). Exception: patients with concomitant mild or moderate pulmonary hypertension or bronchiectasis are permitted to participate.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception (also called basic contraception)methods during the study.
- Patients on any statin therapy with a CK level > 2 X ULN at screening.
Show all 17Show fewer
- Patients who have a clinically significant laboratory abnormality at the screening visit including (but not limited to):
- Total white blood cell count <2500 cells/uL
- AST or ALT > 2.0 X ULN or total bilirubin > 1.3 X ULN
- Estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation or Bedside Schwartz equation <55 mL/minute/1.73 m2.
- Patients with any of the following cardiac related concerns:
- A resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) at screening visit
- A history of familial long QT syndrome or known family history of Torsades de Pointe
- Receiving any medications or other agents known to prolong the QT interval
- patients with a history of moderate or severe uncontrolled tachyarrhythmias
- History of a clinically significant cardiovascular event within 1 year prior to the screening visit, such as acute myocardial infarction, congestive heart failure, unstable arrhythmia
- Patients who, in the judgment of the investigator have a clinically significant ECG abnormality such as (but not limited to) sustained ventricular tachycardia, or clinically significant second or third degree AV block without a pacemaker
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Germany3 sites
Novartis Investigative Site
Frankfurt, 60596
Novartis Investigative Site
Hamburg, 20354
Novartis Investigative Site
Hanover, 30625
United Kingdom1 site
Novartis Investigative Site
Bradford, West Yorkshire, BD9 6RJ
About this study
Official title: A Multi-center, Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in chronic obstructive pulmonary disease (COPD) patients with eosinophilia.
Read the detailed description
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study in COPD subjects with eosinophilia, on standard of care therapy. Standard of care (SoC) treatment in subjects with COPD typically includes a regimen of inhaled corticosteroid (ICS) plus one or more long acting bronchodilator (long-acting beta2-agonist (LABA) or long-acting antimuscarinic antagonist (LAMA)).
The study consisted of a screening period (including an optional pre-screen visit) during which the subject's phenotype and eligibility for the study were assessed. All subjects who met the eligibility criteria after the screening visit were to undergo induction of their sputum to examine the baseline sputum cell counts. Subjects were required to demonstrate both blood and sputum eosinophilia to be eligible for participation in the study.
Eligible subjects were randomized 3:2 to active (fevipiprant 450 mg oral daily) vs. placebo arms. Randomization was stratified by current smoking status (current vs. ex-smoker). Subjects were to continue their COPD standard of care and other medications during the entire course of the study. Subjects were to receive multiple doses of fevipiprant or placebo for six weeks.
Sputum induction was to be repeated at the end of the treatment period and at the end of the study (approximately 4 weeks after the last dose).
The primary purpose of the proof-of-mechanism study was to determine whether fevipiprant (QAW039), when administered to COPD patients with eosinophilic airway inflammation on standard of care therapy, reduced the burden of sputum eosinophilia. Data from other trials did not confirm efficacy of fevipiprant and did not warrant the continuation of treatment in this study. As a result, this study was terminated early.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- QAW039, Placebo
- Keywords
- QAW039, Chronic obstructive pulmonary disease, COPD, sputum, eosinophillic, eosinophilia, prostaglandin D2 receptor, DP2, CRTh2, fevipiprant
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QAW039Drug
QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care
PlaceboDrug
Placebo once daily for 6 weeks administered orally as a tablet + Standard of Care
| Study group | Role | What they receive |
|---|---|---|
| QAW039 450 mg | Experimental | QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet. Receives: Drug: QAW039 |
| Placebo | Placebo comparator | Placebo once daily for 6 weeks administered orally as a tablet. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6
Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count.
As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).
Measured: Baseline, Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2019
- Study start21 May 2019
- Primary completion16 Jan 2020
- Study completion16 Jan 2020
Why it stopped: Company decision
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 Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03810183
- Sponsor's protocol ID
- CQAW039E12201
- Other IDs
- 2018-004267-32, 2018
- Status last verified
- Oct 2021
- First submitted
- 15 Jan 2019
- Last updated
- 8 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia
- ClinicalTrials.gov ID
- NCT03810183
- Acronym / sponsor ID
- CQAW039E12201
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- QAW039, Chronic obstructive pulmonary disease, COPD, sputum, eosinophillic, eosinophilia, prostaglandin D2 receptor, DP2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 May 2019 (actual)
- Primary completion
- 16 Jan 2020 (actual)
- Study completion
- 16 Jan 2020 (actual)
- First posted
- 18 Jan 2019 (actual)
- Results
- Posted 25 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in chronic obstructive pulmonary disease (COPD) patients with eosinophilia.
Detailed description
This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study in COPD subjects with eosinophilia, on standard of care therapy. Standard of care (SoC) treatment in subjects with COPD typically includes a regimen of inhaled corticosteroid (ICS) plus one or more long acting bronchodilator (long-acting beta2-agonist (LABA) or long-acting antimuscarinic antagonist (LAMA)).
The study consisted of a screening period (including an optional pre-screen visit) during which the subject's phenotype and eligibility for the study were assessed. All subjects who met the eligibility criteria after the screening visit were to undergo induction of their sputum to examine the baseline sputum cell counts. Subjects were required to demonstrate both blood and sputum eosinophilia to be eligible for participation in the study.
Eligible subjects were randomized 3:2 to active (fevipiprant 450 mg oral daily) vs. placebo arms. Randomization was stratified by current smoking status (current vs. ex-smoker). Subjects were to continue their COPD standard of care and other medications during the entire course of the study. Subjects were to receive multiple doses of fevipiprant or placebo for six weeks.
Sputum induction was to be repeated at the end of the treatment period and at the end of the study (approximately 4 weeks after the last dose).
The primary purpose of the proof-of-mechanism study was to determine whether fevipiprant (QAW039), when administered to COPD patients with eosinophilic airway inflammation on standard of care therapy, reduced the burden of sputum eosinophilia. Data from other trials did not confirm efficacy of fevipiprant and did not warrant the continuation of treatment in this study. As a result, this study was terminated early.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| QAW039 450 mg | Experimental | Drug: QAW039QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo once daily for 6 weeks administered orally as a tablet. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Acceptable and reproducible spirometry with post-bronchodilator FEV1/FVC < 0.7 and post-bronchodilator FEV1≥ 30 and ≤ 80% of predicted at the screening and baseline visits (GOLD stage II or III COPD).
- Patients with a physician-diagnosed history of COPD for at least 1 year prior to screening visit, and a documented history of at least one COPD exacerbation within the year prior to screening visit and on a stable therapy regimen for COPD for at least 4 weeks prior to screening visit with inhaled glucocorticoid + one or more long acting bronchodilator.
- Current or ex-smokers who have a smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, or equivalent).
- Circulating eosinophils ≥ 300 cells/µL blood AND sputum eosinophils ≥ 3% of total cell count during screening period.
Key exclusion criteria (17 listed)
- Patients with a past or current medical history of asthma.
- Patients with a past or current medical history of conditions other than COPD or allergic rhinitis that could result in elevated sputum eosinophils (e.g., asthma, hypereosinophilic syndrome, Churg-Strauss Syndrome). Patients with known parasitic infestation within 6 months prior to screening are also excluded.
- Patients who have had a respiratory tract infection or COPD worsening or systemic steroid use within 4 weeks prior to screening visit or between screening and randomization visits.
- Patients with history of concomitant chronic or severe pulmonary disease (e.g., sarcoidosis, interstitial lung disease, cystic fibrosis, tuberculosis). Exception: patients with concomitant mild or moderate pulmonary hypertension or bronchiectasis are permitted to participate.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception (also called basic contraception)methods during the study.
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 |
|---|---|---|
| QAW039QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care | Drug | QAW039 450 mg |
| PlaceboPlacebo once daily for 6 weeks administered orally as a tablet + Standard of Care | Drug | Placebo |
Primary outcome
Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6
Time frame: Baseline, Week 6
Sputum eosinophil percentage of the total cell count was obtained from induced sputum samples. Sputum was processed to include preparation of slides for differential cellular count. As sputum eosinophil percentage has been found to follow a log-normal distribution, the analysis of this outcome measure was based on log10-transformed scale. The baseline measurement was defined as sputum eosinophil percentage prior to the first dosing (on log10-transformed scale).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Related trials for Chronic Obstructive Pulmonary Disease
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing QAW039 in people with Chronic Obstructive Pulmonary Disease, run by Novartis Pharmaceuticals at 4 sites in 2 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 4 inclusion and 17 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: stopped early, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, United Kingdom. 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 25 Jan 2021). 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?
Change From Baseline in Sputum Eosinophil Percentage Based on Log-10 Transformed Scale at Week 6 (time frame: Baseline, Week 6). 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 8 Oct 2021.