The purpose of this study is to support the dose selection for the future development program of QBW251 by evaluating efficacy and safety of different QBW251 doses in patients with Chronic Obstructive pulmonary disease (COPD) with chronic bronchitis…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to 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
(LABA/LAMA/ICS). Trough forced expiratory volume in one second (FEV1) will be
assessed at Week 12 and evaluated as change from baseline after 12 weeks of
treatment.
Secondary outcome
Objective 1: To evaluate symptoms (overall COPD symptoms, cough and sputum)
across various dose levels of QBW251 administered orally over 24 weeks,
compared to placebo at Weeks 12 and 24.
Endpoints are
- 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 (PGIS) score.
- Change from baseline in the Cough and Sputum Assessment Questionnaire
(CASA-Q) domain scores - cough symptoms, cough impact, sputum symptoms, and
sputum impact.
Objective 2: To evaluate health-related quality of life across various dose
levels of QBW251 administered orally over 24 weeks, compared to placebo, at
Weeks 12 and 24. The endpoint assessed is the change from baseline in St.
George's Respiratory Questionnaire (SGRQ) total and domain scores at Weeks 12
and 24.
Objective 3: To evaluate lung function across various dose levels of QBW251
administered orally over 24 weeks, compared to placebo, over 4, 8, 16, 20 and
24 weeks. Trough FEV1 change from baseline after 4, 8, 16, 20 and 24 weeks of
treatment, respectively, will be evaluated.
Objective 4: To evaluate safety and tolerability across various dose levels of
QBW251, administered orally over 24 weeks, compared to placebo, as assed by
ECGs, laboratory tests (hematology and clinical chemistry, urinalysis), vital
signs, and adverse events (AEs) per treatment group.
Objective 5: To assess the pharmacokinetics (PK) of QBW251 in COPD patients
through measurement of trough concentration and minimum
concentration (Cmin) on all visits and around maximum concentration (Cmax) on
Days 1, 15 and 169. The area under the plasma concentration-time curve (AUC)
and Cmax on Days 1 and 15 will be assessed in a sub-group of patients.
Background summary
Chronic obstructive pulmonary disease (COPD) is characterized by persistent
respiratory symptoms and airflow limitation that is due to airway and/or
alveolar abnormalities usually caused by significant exposure to noxious
particles/gases, in particular cigarette smoke. COPD is a critically important
disease, with a prevalence of 10% to 15% in Europe. COPD is associated with
episodic periods of symptom deterioration termed exacerbations. Despite
currently available treatments almost 70% of patients remain significantly
limited by breathlessness, therefore additional novel therapies are urgently
needed.
Study objective
The purpose of this study is to support the dose selection for the future
development program of QBW251 by evaluating efficacy and safety of different
QBW251 doses in patients with Chronic Obstructive pulmonary disease (COPD) with
chronic bronchitis and a history of exacerbations. QBW251 treatment will be
added on top of a triple combination therapy of a long-active beta2-agonist
(LABA), a long-acting muscarinic receptor-antagonist (LAMA) and an inhaled
corticosteroid (ICS).
Study design
This study uses a 5 treatment arm, parallel-group, randomized, double-blind
study design. The study is placebo-controlled with a standardized COPD
background treatment. The treatment period lasts 24 weeks, the total duration
of study participation for a patient is 31 weeks.
Intervention
- Treatment arm 1: QBW251, 300 mg, b.i.d.
- Treatment arm 2: QBW251, 150 mg, b.i.d.
- Treatment arm 3: QBW251, 75 mg, b.i.d.
- Treatment arm 4: QBW251, 25 mg, b.i.d.
- Treatment arm 5: Placebo matching QBW251, b.i.d.
All patients are receiving standardized background COPD medication consisting
of fluticasone furoate, umeclinidium and vilanterol.
Study burden and risks
Potential burden and risk for participants includes potential side effects of
study medication, time investment and additional tests and examinations.See
protocol, Investigator's Brochure and above for additional information on risk
and benefits.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
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.
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003197-28-NL |
| CCMO | NL69760.056.19 |