A two part, double blind, placebo controlled, study to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple doses of QBM076 in patients with COPD

• Register: EUCTR
• Last refreshed on: 16 August 2016
• Main ID: EUCTR2012-005615-92-BE
• Date of registration: 28/11/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A two part, double blind, placebo controlled, study to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple doses of QBM076 in patients with COPD
• Scientific title: A two part, double blind, placebo controlled, study to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple doses of QBM076 in patients with COPD
• Date of first enrolment: 19/12/2014
• Target sample size: 122
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005615-92
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Hungary, Netherlands, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novaryis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novaryis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Part 1:
- Patients, smokers or ex-smokers with stable chronic bronchitis GOLD
class I-III COPD according to the current GOLD strategy (GOLD 2013)
- FEV1 =40% of predicted and FEV1:FVC ratio =0.7 post bronchodilator
- DLCO =40%; a stable medical regimen for at least 4 weeks prior to
screening.
Current smokers can be enrolled if they currently smoke =1ppd for last 3
months.
• Part 2:
- Patients with stable chronic bronchitis GOLD class I-III COPD
according to the current GOLD strategy (GOLD 2013)
- a stable medical regimen for at least 4 weeks prior to screening
- hsCRP=1.5 mg/L; FEV1 =40% of predicted and FEV1:FVC ratio =0.7
post bronchodilator, respectively with LCI=8
- ex-smokers with at least 10 pack year smoking history or current
smokers with at least 10 pack
year smoking history who smoke = 1ppd on average for last 3 months.
- evidence on HRCT of airway thickening by visual inspection

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 82

Exclusion criteria:
• Part 1:
- Gold Class IV COPD, of moderate to significant emphysema, or
evidence of malignancy
- medication considered potential for DDI
- CrCl <40ml/min
- more than 1 exacerbation requiring antibiotics or oral steroids and/or
hospitalization within 3 months of screening
- women of child bearing potential
• Part 2:
- Gold Class IV COPD
- medication considered a potential for DDI
- serum creatinine =1.9 mg/dL
- more than 1 exacerbation requiring antibiotics or oral steroids and/or
hospitalization within 3 months of screening
- current smokers
- any malignancy
- HRCT chest screen failure based on preset criteria for bronchial
thickening, emphysematous changes and extent of bronchiectasis
- use of oral steroids, theophylline, PDE4 inhibitors or oral antibiotic use
(eg.macrolides)
- women of child bearing potential


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 17.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Code: QBM076
Pharmaceutical Form: Capsule, hard
Current Sponsor code: QBM076
Other descriptive name: QBM076
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: QBM076
Pharmaceutical Form: Capsule, hard
Current Sponsor code: QBM076
Other descriptive name: QBM076
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Part 1: To evaluate the safety and tolerability of multiple ascending
doses of QBM076 in current or ex-smoking patients with chronic
bronchitis stable COPD classes I-III (according to the current GOLD
strategy (GOLD 2013)) for 14 consecutive days of treatment.
Part 2: To evaluate the preliminary efficacy of 56 consecutive days of
QBM076 in current or ex-smoking patients with stable chronic bronchitis
COPD classes I-III (according to the current GOLD strategy (GOLD
2013)).
1. LCI;
2. absolute neutrophil count in induced sputum;
3. spirometry FEV1;
4. TDI.

Timepoint(s) of evaluation of this end point: Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

Primary end point(s): Part 1:
The primary variable for the safety objective is occurrence of an adverse event in multiple doses of QBM076 for 14 days of treatment.

Part 2:
The primary variables for the efficacy objective are LCI, absolute number of sputum neutrophils, FEV1 and TDI.

Secondary Objective: Part 1
• To evaluate the pharmacokinetics of multiple doses of QBM076 for 14
consecutive days.
• To evaluate the effects of multiple doses of QBM076 for 14 consecutive
days on CD11b inhibition, CXCR2 receptor occupancy, LCI and PFTs
Part 2
• safety and tolerability of multiple doses of QBM076 in chronic
bronchitis current or ex-smoking COPD patients for 56 consecutive days
• pharmacokinetics of multiple doses of QBM076 for 56 consecutive days
• preliminary efficacy at Day 56 of multiple doses of QBM076 in chronic
bronchitis COPD patients as reflected in changes in:
• Measurements associated with MBNW
• Change in % sputum neutrophils in induced sputum
• FEF25-75, FEV3/FVC, 1-(FEV3/FVC), FEV6, FEV1/FEV6 and postbronchodilator
FEV11 measured by spirometry
• Additional PFT measurements performed in a body plethysmography
box including DLCO, IC, FRCTLC, RV and RV/TLC ratio
• Assessment of air trapping as assessed by the exhalation phase of the
HRCT

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

Secondary end point(s): Efficacy / Pharmacodynamics
Part 1
To evaluate the pharmacodynamic response to multiple doses of QMB076 in COPD patients as reflected by changes in LCI, sputum neutrophils, and lung function to Day 14.

Part 2
Secondary and exploratory pharmacodynamic variables include
respiratory resistance as measured by FOT, PFT measurements
performed in a body plethysmography box including, DLCO, FVC,
FVC/FEV1 ratio, CD11b expression, neutrophils shape change, CXCR2
receptor occupancy in whole blood. The descriptive statistics for each
variable will be provided by treatment for each part of the study.

Safety

Vital signs
All vital signs data will be listed by treatment, subject, and visit/time and if ranges are available abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics will be provided by treatment and visit/time.

ECG evaluations
All ECG data will be listed by treatment, subject and visit/time, abnormalities will be flagged. Summary statistics will be provided by treatment and visit/time.

Clinical laboratory evaluations
All laboratory data will be listed by treatment, subject, and visit/time and if normal ranges are available abnormalities will be flagged. Summary statistics will be provided by treatment and visit/time.

Adverse events
All information obtained on adverse events will be displayed by treatment and subject. The number and percentage of subjects with adverse events will be tabulated by body system and preferred term with a breakdown by treatment. A subject with multiple adverse events within a body system is only counted once towards the total of this body system.

Pharmacokinetics (including exploratory assessment of dose proportionality)

Pharmacokinetic / pharmacodynamic interactions
An exploratory analysis of the relationship between pharmacokinetic and pharmacodynamic measures will be explored using a model based approach, if the data permits.

Secondary ID(s)

CQBM076X2203

2012-005615-92-DE

Source(s) of Monetary Support

Novartis Pharma Services AG