Clinical Trials Register

Summary
EudraCT Number:	2012-005615-92
Sponsor's Protocol Code Number:	CQBM076X2203
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-02-05
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2012-005615-92

A.3

Full title of the trial

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

Kétszakaszos, kettősvak, placebo kontrollált vizsgálat a többszörös dózisban alkalmazott QBM076 biztonságosságának, tolerálhatóságának, farmakokinetikai és farmakodinámiás hatásainak vizsgálatára COPD betegek esetén

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

CQBM076X2203

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Hungary Kft. Pharma
B.5.2	Functional name of contact point	Public Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Bartók Béla út 43-47.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1114
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+361457-6500
B.5.5	Fax number	+361457-6600
B.5.6	E-mail	infoph.hungary@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	QBM076
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	QBM076
D.3.9.3	Other descriptive name	QBM076
D.3.9.4	EV Substance Code	SUB32050
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	QBM076
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	QBM076
D.3.9.3	Other descriptive name	QBM076
D.3.9.4	EV Substance Code	SUB32050
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

Smokers cough

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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 current or ex-smoking COPD patients for 8 consecutive weeks
• pharmacokinetics of multiple doses of QBM076 for 8 consecutive weeks
• preliminary efficacy at 8 weeks of multiple doses of QBM076 in COPD patients as reflected in changes in:
• Measurements associated with MBNW
• Change in % neutrophils in sputum
• FEF25-75, FEV3/FVC, 1-(FEV3/FVC), FEV6, FEV1/FEV6 and post-bronchodilator 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

E.2.3

Trial contains a sub-study

E.3

Principal 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)
- 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 GOLD spirometry grades 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 ≥30% 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
- 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.

E.4

Principal exclusion criteria

• Part 1:
- Gold Grade IV COPD, moderate to significant emphysema, or
evidence of active 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 daily oral steroids, theophylline, PDE4 inhibitors or oral antibiotic use (eg.macrolides)

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

E.5.2

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

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Global LPLV (LVLS)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

122

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No post trial treatment foreseen.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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