Clinical Trials Register

Summary
EudraCT Number:	2019-000325-49
Sponsor's Protocol Code Number:	CQBW251B2202
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2020-04-09
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

Germany - BfArM

A.2

EudraCT number

2019-000325-49

A.3

Full title of the trial

A randomized, subjects and investigator blinded, placebo controlled parallel group study to assess the mode of action of QBW251 in patients with Chronic Obstructive Pulmonary Disease (COPD)

A.3.1

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

Clinical Study to Assess the Mode of Action of QBW251 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A.4.1

Sponsor's protocol code number

CQBW251B2202

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 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 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 Pharma GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice (MCC)
B.5.3	Address:
B.5.3.1	Street Address	Roonstrasse 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 911 273-12100
B.5.5	Fax number	+49 911 27312160
B.5.6	E-mail	infoservice.novartis@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	QBW251
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.3.8	INN - Proposed INN	Icenticaftor
D.3.9.2	Current sponsor code	QBW251
D.3.9.3	Other descriptive name	CFTR potentiator
D.3.9.4	EV Substance Code	SUB73414
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	300
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

E.1.1.1

Medical condition in easily understood language

Chronic obstructive airways disease

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10029972
E.1.2	Term	Obstructive airways disease (chronic)
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

To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on fibrinogen plasma concentration.

E.2.2

Secondary objectives of the trial

•To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on:
a)sputum bacterial load
b)airway structure and function
c)COPD subjects patients symptom burden changes
d)health status
e)changes in health-related quality of life
f)COPD exacerbations
g)clinical symptoms, cough and sputum
h)pharmacokinetics
i)spirometry
•To assess the safety and tolerability of QBW251 in subjects with COPD

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Patients who have signed an Informed Consent Form prior to initiation
of any study-related procedure.
•Male and female adults aged ≥40 years at screening.
•Patients with stable COPD, stages GOLD 2-3, according to the current
GOLD strategy (GOLD 2019) at screening.
•Patients with a post-bronchodilator FEV1/FVC < 0.70 at screening
•Patients with airflow limitation indicated by a post-bronchodilator FEV1
≥ 30% and FEV1 < 80% of the predicted normal at Screening who must
have had at least 2 documented moderate or at least 1 documented
severe exacerbation(s) between January 2019 to study screening.
• Patients with sputum positive (>0 CFU) for at least one
strain of potentially pathogenic microorganism at screening (H
influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas
maltophilia, Burkholderia species, and Achromobacter species or any
potential pathogenic bacteria measured by dilution/outgrowth. Any
organism that is to be included and that is not included in the list of the
protocol defined pathogens will be discussed case by case). Sputum
samples may be re-collected and re-tested once during the screening
period.
•Patients who have been treated with a combination of LABA/LAMA or
LABA/ICS or LABA/LAMA/ICS at a stable dose for the last 3 months
prior to screening.
COPD patients are allowed to stay on macrolides as background therapy
if they have bronchiectasis as a secondary diagnosis and if they are
treated with them at a stable dose 3 months before screening.
•Patients with plasma fibrinogen level ≥320 mg/dL at screening.
Fibrinogen may be re-tested once during the screening period.
•A COPD Assessment Test (CAT) score of at least 10 at screening.
•Current or ex-smokers who have a smoking history of at least 10 pack
years at screening. (e.g. 10 pack years = 1 pack/day x 10 years, or 0.5
pack/day x 20 years) at screening.
•Patients featuring chronic bronchitis, defined as productive cough that
occurs on most days (defined as >50% of days) during at least 3
consecutive months in the year prior to screening, as assessed by
documentation of patient recollection(anamnesis) or documented in
patients' records.

E.4

Principal exclusion criteria

•Patients with a history of long-QT syndrome or whose QTcF interval at
screening (Fridericia method) is prolonged (QTcF >450 ms in males,
>460 ms in females).
•Patients who have a clinically significant ECG abnormality before
randomization.
•Clinical laboratory values abnormalities (including Gamma GT, AST,
ALT, total bilirubin or creatinine) considered as clinically significant in
the opinion of the Investigator at screening.
•Patients who have clinically significant renal, cardiovascular (such as
but not limited to unstable ischemic heart disease, NYHA Class III/IV
left ventricular failure, myocardial infarction), neurological, endocrine,
immunological, psychiatric, gastrointestinal, or hematological
abnormalities, which could interfere with the assessment of the efficacy
and safety of the study treatment, or patients with uncontrolled Type II
diabetes.
•Patients with a history or current treatment for hepatic disease
including but not limited to acute hepatitis, cirrhosis or hepatic failure.
-Patients with stable chronic hepatitis may be included in the study by
agreement with Novartis Medical Expert on a case-by-case basis.
-A history of resolved Hepatitis A is not exclusionary.
-Patients with prothrombin time international normalized ratio
(PT/INR) of more than 1.5xULN at screening. Patients excluded for the
PT/INR of more
than 1.5xULN can be re-screened when the values have returned to
normal.
•Patients with a history of malignancy of any organ system, treated or
untreated, within the past 5 years whether or not there is evidence of
local recurrence or metastases, with the exception of localized basal cell
carcinoma of the skin. Patients with a history of cancer and 5 years or
more disease free survival time may be included in the study by
agreement with Novartis Medical Expert on a case-by-case basis.
•Patients who develop a COPD exacerbation that required treatment
with antibiotics and/or oral corticosteroids and/or hospitalization during screening. Re-screening is permitted after a minimum of 2 weeks after
the resolution of the COPD exacerbation (i.e. 2 weeks after the stop of
SOC therapy for exacerbation).
•Patients who have had a respiratory tract infection within 4 weeks
prior to screening. If a respiratory tract infection occurs during
screening, patients can be re-screened after a minimum of 2 weeks after
resolution of the respiratory tract infection.
•Patients with history of asthma or any other clinically relevant lung
diseases.
•Patients with suspected active pulmonary tuberculosis or currently
being treatment for active pulmonary tuberculosis.
Note: Patients with a history of pulmonary tuberculosis can be enrolled if
they meet the following requirements: history of appropriate drug
treatment followed by negative imaging results within 12 months prior
to screening suggesting low probability of recurrent active tuberculosis.
•Patients with pulmonary lobectomy, lung volume reduction surgery,
bronchoscopic lung volume reductions, or lung transplantation.
•Patients participating in or planning to participate in the active phase of
a supervised pulmonary rehabilitation program during the trial.
Participation in a maintenance program is permitted. Note: the
supervised pulmonary rehabilitation program as a maintenance program
has to be ongoing for at least 3 months at the time of enrollment.
•Patients with a body mass index (BMI) of more than 40 kg/m2.
•Pregnant or nursing (lactating) women where pregnancy was defined
as the state of a female after conception and until the termination of
gestation, confirmed by a positive human chorionic gonadotropin (hCG)
laboratory test.
•Women of childbearing potential defined as all women physiologically
capable of becoming pregnant,unless they are using acceptable effective
methods of contraception during study participation.
•Patients who have not achieved an acceptable spirometry result at
screening in accordance with American Thoracic Society (ATS)/European
Respiratory Society (ERS) criteria for acceptability and repeatability.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in fibrinogen plasma concentration.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks of treatment

E.5.2

Secondary end point(s)

•Change from baseline in total bacteria load of colony forming units (CFU/mL) of potentially pathogenic microorganisms in sputum.
•Change from baseline in airway wall and lumen parameters along with extent of global and regional air trapping, as measured by HRCT.
•Change from baseline in COPD Assessment Test (CAT) questionnaire.
•Changes from baseline in the Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) questionnaire.
•Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total and domain scores.
•Time to first COPD exacerbation, Proportion of subjects with exacerbations and Annualized rate of exacerbations as defined by EXACT-PRO questionnaire.
•Change from baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) domain scores.
•Assessment of safety and tolerability (ECG intervals, vital signs, standard clinical laboratory Evaluations, adverse Events)
•Assessment of drug exposure (Ctrough collected at pre-dose and Cmax at post-dose +3hr) on Day 1, Day 28, Day 56 and Day 84. Cmax and AUC post-dose (+1hr, +2hr, +3hr, +4hr, +6hr, +8hr) on Day 1 and Day 28 in a subset of subject population
•Change from baseline in trough FEV1, FVC, and FEV1/FVC.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks of treatment

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

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and Mode of action

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

Austria

Switzerland

Germany

United Kingdom

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

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

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)

Yes

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

100

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)

None

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

2020-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-09

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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