A study to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple doses of QBM076 in patients with COPD

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2012-005615-92-NL
• Date of registration: 22/12/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 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: 01/04/2015
• 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

Countries of recruitment

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

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services AG

Key inclusion & exclusion criteria

Inclusion criteria:
Part 1:
- 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 bronchodilatation.
- Current smokers can be enrolled if they currently smoke =1ppd for last 3 months.
- Post bronchodilator FEV1 at screening =40% of predicted.
- DLCO =40% at screening.
- A stable medical regimen for at least 4 weeks prior to screening.

Part 2:
- 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.
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) no
F.1.3.1 Number of subjects for this age range 82

Exclusion criteria:
Part 1:
- Gold Class IV COPD.
- Moderate to significant emphysema.
- History of malignancy within the past 5 years prior to screening.
- Medication considered potential for DDI.
- Estimated CrCl < 30ml/min at screening.
- More than 1 exacerbation requiring antibiotics or oral steroids in the 8 weeks prior to screening and/or hospitalization in the 3 months prior to screening.
- Use of oral corticosteroids, theophylline (within 1 week priot to screening), PDE4 inhibitors or oral antibiotic use (e.g., macrolides).

Part 2:
- 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 priot to screening), PDE4 inhibitors or oral antibiotic use (e.g., macrolides).


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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Product Code: QBM076
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not available
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
INN or Proposed INN: Not available
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)

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:
-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.
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.

Main Objective: Part 1:
To evaluate the safety and tolerability of multiple ascending doses of QBM076 in current or ex-smoking patients with stable COPD with spirometry grades I-III (according to the current GOLD strategy (GOLD 2013) for 14 consecutive days of treatment.

Part 2:
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).
1. LCI
2. absolute neutrophil count in sputum
3. spirometry FEV1
4. TDI

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.

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

Secondary Outcome(s)

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, and FVC/FEV1 ratio. The descriptive statistics for each variable will be provided by treatment for each part of the study.

Safety Part 1 and 2:

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) Part 1 and 2:

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.

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

Secondary ID(s)

CQBM076X2203

2012-005615-92-DE

Source(s) of Monetary Support

Novartis Pharma Services AG