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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Characterize the dose-response relationship of QBW251
administered orally over 12 weeks on lung function,
compared to placebo when added to inhaled triple
combination therapy (long-acting β2-agonist / long-acting
muscarinic receptor antagonist / inhaled corticosteroid;
LABA/LAMA/ICS). |
|
E.2.2 | Secondary objectives of the trial |
-Evaluate COPD symptoms across various dose levels of QBW251
administered orally over 24 weeks, compared to placebo
-Evaluate health-related quality of life across various dose
levels of QBW251 administered orally over 24 weeks,
compared to placebo
-Evaluate lung function across various dose levels of
QBW251 administered orally over 24 weeks, compared to
placebo
-Assess the pharmacokinetics of QBW251 in COPD
patients |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female COPD patients aged ≥40 years,
who have signed an Informed Consent Form prior to
initiation of any study-related procedure.
• Current or ex-smokers who have a smoking
history of at least 10 pack years.
• Patients who have been treated with a triple
combination of LABA/LAMA/ICS for the last 3 months
prior to screening.
• A COPD Assessment Test (CAT) score of at
least 10 at Run-In 1 visit.
• Patients with a post-bronchodilator FEV1/FVC <
0.70 at Run-In 1 visit.
• Patients with airflow limitation indicated by
EITHER
a post-bronchodilator FEV1 ≥ 30 % and FEV1 < 50 %
of the predicted normal at Run-in 1, who must have
had at least 1 documented moderate or severe
healthcare resource utilization (HCRU) exacerbation
in the 12 months prior to study entry (screening),
OR
a post-bronchodilator FEV1 ≥ 50 % and <80 % of the
predicted normal at Run-In 1, who must have had at
least 2 documented moderate or at least 1
documented severe HCRU exacerbation(s) in the 12
months prior to study entry (screening)
• Patients featuring chronic bronchitis, defined by
the presence of cough and bronchial hypersecretion,
that occurs for at least three consecutive months in
each of two consecutive years prior to study entry
(screening), documented in patient history. |
|
E.4 | Principal exclusion criteria |
• Patients who have a history of long-QT
syndrome, a clinically significant ECG abnormality at
baseline, or whose QTc measured at baseline is
prolonged.
• Patients who have clinically significant renal,
cardiovascular, neurological, endocrine,
immunological, psychiatric, gastrointestinal, or
hematological abnormalities, which could interfere
with the assessment of the efficacy and safety of the
study treatment, with a clinically significant laboratory
abnormality at baseline, or patients with Type I
diabetes or uncontrolled Type II diabetes.
• Patients who have had a COPD exacerbation
that required treatment with antibiotics and/or oral
corticosteroids and/or hospitalization, or a respiratory
tract infection in the 4 weeks prior to screening, or
between screening and randomization.
• Patients with any documented history of asthma,
or with an onset of chronic respiratory symptoms,
including a COPD diagnosis, prior to age 40 years.
• Patients with a body mass index (BMI) of more
than 40 kg/m2.
• Use of other investigational drugs (approved or
unapproved) within 30 days or 5 half-lives prior to
screening, or until the expected pharmacodynamic
effect has returned to baseline (e.g., biologics),
whichever is longer; or longer if required by local
regulations.
• Pregnant or nursing (lactating) women, and
women of childbearing potential not willing to use
acceptable effective methods of contraception during
study participation. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Trough FEV1 change from
baseline after 12 weeks of
treatment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in the
Evaluating Respiratory
Symptoms in COPD (E-RS)
weekly mean scores (total
and subscale scores).
Change from baseline in
Patient Global Impression of
Severity (PGI-S) score.
Change from baseline in the Cough and Sputum
Assessment Questionnaire
(CASA-Q) domain scores -
cough symptoms, cough
impact, sputum symptoms,
and sputum Impact.
- Change from baseline in St.
George's Respiratory
Questionnaire (SGRQ) total
and domain scores at weeks
12 and 24
- Trough FEV1 change from
baseline after 4, 8, 16, 20
and 24 weeks of treatment,
respectively
- Assessment of drug
exposure (trough
concentration; Cmin) on all
visits and around Cmax on
Days 1, 15 and 169. AUC
and Cmax on Days 1 and 15
in a subset of patients |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Specified in the endpoints descriptions |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Belgium |
Canada |
Colombia |
Czechia |
Denmark |
France |
Germany |
Greece |
Guatemala |
Hong Kong |
Hungary |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Philippines |
Poland |
Slovakia |
Spain |
Thailand |
Turkey |
United Kingdom |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |