Primary Obejective:To evaluate the preliminary efficacy of 8 consecutive weeks of QBM076 in current or ex-smoking patients with stable COPD with spirometry grades I-III (according to the current GOLD strategy (GOLD 2013).Secondary Objectives:To…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- LCI
- Absolute number of sputum neutrophils
- FEV1
- TDI.
Secondary outcome
- Respiratory resistance
- All vital signs data
- All ECG data
- All laboratory data
- All information obtained on adverse events
- An exploratory analysis of the relationship between pharmacokinetic and
pharmacodynamic measures.
Background summary
COPD is a progressive condition that is a major cause of poor health and death
worldwide and contributes significantly to health care costs and comorbidity.
COPD is a highly heterogeneous disease that is characterized by poorly
reversible airflow limitation that is progressive, and associated with abnormal
inflammatory response of the lung. By suppressing neutrophil influx it is
postulated that reduced inflammation and/or increased repair will take place.
QBM076 choline salt is an orally administered low molecular weight CXCR2
antagonist specifically developed for the treatment of COPD. Inhibition of
CXCR2 receptor in vivo with QBM076 will block neutrophil migration. By reducing
CXCR2 activation, it is postulated inflammation within the lung will be reduced
resulting in improved function of the small airways and a slowdown of tissue.
Recently, COPD has been determined to be a progressive and potentially
reversible disease beginning and manifesting pathology throughout the disease
process in the small airways. As the disease progresses, the large airways
become involved. Current standards of treatment efficacy focus on PFTs, and in
particular, FEV1, which is a measure primarily of the larger conducting
airways. This study focuses on COPD patients with measurable small airway
disease, physiologically and phenotypically, to preselect patients who may have
the greatest benefit from QBM076, a selective CXCR2 inhibitor.
The improvement of the ventilation and perfusion of smaller airways of the lung
with concomitant improvement in their function, will result in either
prevention of further deterioration or clinical improvement in longer studies
manifested by fewer exacerbations. Thus there may be an improvement in both the
quality and quantity COPD patients* lives through a novel mechanism of action.
Study objective
Primary Obejective:
To evaluate the preliminary efficacy of 8 consecutive weeks of QBM076 in
current or ex-smoking patients with stable COPD with spirometry grades I-III
(according to the current GOLD strategy (GOLD 2013).
Secondary Objectives:
To assess the safety and tolerability of multiple doses of QBM076 in current or
ex-smoking COPD patients for 8 consecutive weeks
* To evaluate the pharmacokinetics of multiple doses of QBM076 for 8
consecutive weeks
* To evaluate the preliminary efficacy after 8 consecutive weeks of multiple
doses of QBM076 in COPD patients as reflected in changes in:
- Measurements associated with MBNW such as Scond and Sacin, trapped gas
volume, closing volume
- Change in % sputum neutrophils in sputum
- FEF25-75, FEV3/FVC, 1-(FEV3/FVC), FEV6, FEV1/FEV6 and post-bronchodilator
FEV1 measured by spirometry
- Additional PFT measurements performed in a body plethysmography box including
DLCO, IC, FRC, TLC, RV and RV/TLC ratio
- Assessment of the change from baseline in quantitative air trapping as
assessed by HRCT
Study design
This is a two part, double-blind placebo-controlled study of the safety,
tolerability, pharmacokinetic and pharmacodynamic effects of multiple doses
QBM076 in patients with COPD. Part 1 has been completed in which the
Netherlands has not participated. Netherlands participates in Part 2.
Part 2 of this study begins with a screening of a maximum of 30 days, followed
by a treatment period (QBM076 / placebo) of 8 weeks. Approximately one week
after the treatment period, there is a final end of study visit (control). For
each subject the total duration of the study is approximately 14 weeks and
approximately 12 visits will be performed.
Intervention
Treatment with QBM076 150 mg / placebo (oral): daily, for 8 weeks.
Study burden and risks
Disadvantages of participating is the risk of side effects from the study
medication and discomfort of the test procedures.
Possible side effects of QBM076:
Headache (most often reported) and increase sensitivity to sunlight / UV light.
Inconvenience/Risk of the studyprocedures:
- Blood prick; local pain, bruising, scab infection.
- During the blowing of a lung; headache, chest pressure or light-headedness.
After inhalation of salbutamol: tremors or palpitations.
- When coughing up sputum: chest tightness, wheezing, light-headedness or an
unpleasant taste in the mouth.
- When a CT scan is radiation-free, however very gering.Tijdens staying in the
scanner; suffer from anxiety in a small space (claustrophobia).
Burden:
- Physical examination: 6x
- Blood pressure and pulse: 12x
- Temperature, oxygen content: 12x
- Blood collection/tests: 12x
- Pregnancy test (female subjects): 6x
- Urinalysis: 7x
- ECG: 9x
- PFT spirometry: 8x
- PFT bodybox: 4x
- Induced sputum : 5x
- CT Scan: 1-2x.
- Completing two questionnaires (BDI and TDI): 2x.
- Completion of a Diary: During entire study period.
Optional:
Additional blood collection for pharmacogenetic analysis: 1x
There are prohibited medications. See protocol section 5.5.9 page 63 for
details.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
Part 2 of protocol:
- Patients, smokers or ex-smokers with stable GOLD spirometry grades I-III COPD according to the current GOLD strategy (GOLD 2013). COPD is defined as patients with FEV1/FVC ratio *0.7 after bronchodilation.
- Current smokers with at least 10 pack years can be enrolled if they currently smoke *1ppd for last 3 months.
- A stable medical regimen for at least 4 weeks prior to screening.
- hsCRP * 1.5 mg/L at screening and baseline visit.
- Post-bronchodilator FEV1 at screening * 30% of predicted.
- Mean LCI 2.5% * 8 at screening.
- Evidence of air trapping on HRCT.
- Women of child bearing potential can be enrolled as long as they agree to use effective contraception (except hormonal contraceptives, due to the risk of drug-drug interaction with QBM076) as described in the protocol.
Exclusion criteria
Part 2 of protocol:
- Gold Class IV COPD
- Medication considered potential for DDI.
- Estimated CrCl < 30ml/min at screening.
- Serum creatinine *1.9 mg/dL at screening.
- More than 1 exacerbation requiring antibiotics or oral steroids in the 8 weeks prior to screening and/or hospitalization in 3 months prior to screening.
- History of malignancy within the past 5 years prior to screening.
- HRCT chest screen failure based on preset criteria for air trapping, emphysematous changes and extent of bronchiectasis
- Use of oral corticosteroids, theophylline (within 1 week prior to screening), PDE4 inhibitors or oral antibiotic use (e.g., macrolides).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005615-92-NL |
| ClinicalTrials.gov | NCT01972776 |
| CCMO | NL51583.058.14 |