NCT04072887

Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients

A 24-week Multi-center, Double-blind, Placebo Controlled Dose-range Finding Study to Investigate the Efficacy and Safety of Oral QBW251 in COPD Patients on Triple Inhaled Therapy (LABA / LAMA / ICS)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 974 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

Summary

This clinical study was designed to support the dose selection for future studies by evaluating efficacy and safety of different QBW251 doses in Chronic obstructive pulmonary disease (COPD) patients with chronic bronchitis and a history of exacerbations, compared to placebo, when added to a triple inhaled therapy of LABA, LAMA and ICS.

Detailed description

This study used a 6 treatment arm, parallel-group, randomized, double-blind study design. 974 male and female COPD patients were randomized into the trial. The study consisted of four distinct study periods: * Screening (Weeks -3 to -2): Participants underwent a screening period of 1 week where were assessed for eligibility and tapered off disallowed medications. * Run-in (Days -14 to 1): Subsequently, participants entered the run-in period of up to 2 weeks to establish baseline values for symptom assessments, to standardize the COPD background therapy (triple combination LABA/LAMA/ICS), and to complete eligibility assessments. * Treatment (Day 1 to Week 24): Eligible participants moved into the Day 1 visit where they were stratified according to their smoking status (current or ex-smoker) and severity of airflow limitation (FEV1 ≥ 30% to \< 50% and ≥ 50% to \< 80%) and then randomized into 1 of 6 treatment arms with a randomization ratio of 2:2:1:1:1:2 (450 mg b.i.d., 300 mg b.i.d., 150 mg b.i.d., 75 mg b.i.d., 25 mg b.i.d., placebo). The treatment period consisted of 24 weeks, during which the participant returned to the site for regular visits (Day 1 - Week 24). QBW251 450 mg arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule. * Follow-up (Weeks 25-28): Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.

Conditions

• Pulmonary Disease, Chronic Obstructive

Interventions

Type	Name	Description
DRUG	QBW251	QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
DRUG	Placebo	Placebo oral capsules administered twice a day for 24 weeks
DRUG	COPD maintenance background therapy	Combination of fluticasone furoate, vilanterol and umeclidinium bromide

Timeline

• Start date: 2019-09-12
• Primary completion: 2021-10-08
• Completion: 2022-02-01
• First posted: 2019-08-28
• Last updated: 2023-04-28
• Results posted: 2023-04-28

Locations

148 sites across 26 countries: United States, Argentina, Australia, Austria, Belgium, Canada, Colombia, Czechia, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Italy, Japan, Netherlands, Philippines, Poland, Slovakia, South Korea, Spain, Thailand, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study