A 24-week study to investigate dose, efficacy and safety of QBW251 in patients with chronic obstructive airways disease, given on top of triple inhaled therapy (LABA/LAMA/inhaled corticosteroids)
- Conditions
- Chronic obstructive pulmonary diseaseMedDRA version: 21.1Level: LLTClassification code 10029972Term: Obstructive airways disease (chronic)System Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-003197-28-FR
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 900
• 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.
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 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 450
• 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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 ß2-agonist / long-acting muscarinic receptor antagonist / inhaled corticosteroid; LABA/LAMA/ICS).;Secondary Objective: -Evaluate COPD symptoms across various dose levels of QBW251 administered orally over 24 weeks, compared to placebo <br>-Evaluate health-related quality of life across various dos levels of QBW251 administered orally over 24 weeks, compared to placebo<br>-Evaluate lung function across various dose levels of QBW251 administered orally over 24 weeks, compared to placebo<br>-Assess the pharmacokinetics of QBW251 in COPD patients ;Primary end point(s): Trough FEV1 change from baseline after 12 weeks of treatment;Timepoint(s) of evaluation of this end point: 12 weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in the Evaluating Respiratory Symptoms in COPD (E-RS) weekly mean scores (total and subscale scores).<br>- Change from baseline in Patient Global Impression of Severity (PGI-S) score.<br>- Change from baseline in the Cough and Sputum Assessment Questionnaire (CASA-Q) domain scores - cough symptoms, cough impact, sputum symptoms, and sputum Impact.<br>- Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total and domain scores at weeks 12 and 24<br>- Trough FEV1 change from baseline after 4, 8, 16, 20 and 24 weeks of treatment, respectively<br>- 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<br>in a subset of patients;Timepoint(s) of evaluation of this end point: Specified in the endpoints descriptions