A randomised study of QBW251 in patients with bronchiectasis
Research type
Research Study
Full title
A randomized, subject- and investigator-blinded, placebo controlled, parallel group study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of QBW251 in patients with bronchiectasis
IRAS ID
287333
Contact name
James Chalmers
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2019-002840-26
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 1 months, 20 days
Research summary
Research Summary
Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more likely to suffer from infections; these infections can often be linked to an increased chance of hospitalisation and early death. The most common symptoms include a persistent cough that usually brings up mucus (or sputum) and breathlessness. Bronchiectasis can progress gradually over time causing significant symptoms and overall poor quality of life for patients. At present, the treatment options are limited; as such there is a high unmet need for new therapy options.
QBW251 is an experimental drug designed to improve mucus clearance and reduce the level of bacteria in the lungs. This study will primarily look at how effective QBW251 is in reducing and clearing the amount of mucus in the lungs and whether the levels of bacteria in the mucus are reduced, thereby reducing airway obstruction and inflammation. Improvements in lung function, quality of life and clinical symptoms will also be assessed. Safety of the drug will be continually monitored throughout the course of the trial.
Both male and female bronchiectasis participants, over the age of 18, will be recruited and randomly assigned to receive either the trial drug, QBW251, or matching placebo (dummy drug) in a 1:1 ratio. QBW251/placebo will be taken twice a day, by mouth, for 12 weeks. Approximately 72 participants will be recruited globally, with the intention of fully treating 60 participants.
The study will consist of the following periods: Screening, baseline/Day 1, treatment period, and end of study assessments visit followed by an additional post-treatment safety follow up via a phone call. The total duration for each participant in the study is up to approximately 18 weeks.
The sponsor of this study is Novartis Pharma AG.
Summary of Results
Novartis Pharma AG (the study sponsor), on behalf of the Contract Research Organization TMC and its subcontractors, thanks all patients, site personnel and investigators for participating in the completed study: “A randomized, subject- and investigator-blinded, placebo-controlled, parallel group study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of QBW251 in patients with bronchiectasis”.
The drug (QBW251) is used for the treatment of the respiratory condition, Bronchiectasis. Bronchiectasis is usually the result of a respiratory infection or other conditions that damage the airway walls or prevent the airways from clearing mucus.
The drug aims to improve the clearance of mucus, reduce infection, reduce exacerbations and improve lung function and quality of life for patients.
The 12- week study compared the drug QBW251, with a placebo. A placebo is a capsule that looks identical but does not contain any active ingredient. Patients received either QBW251 at a dose of 300 mg per capsule or the placebo.
42 patients with Bronchiectasis participated in the study, half received the drug QBW251, and the other half received the placebo. The study consisted of the screening, baseline/Day 1, treatment period, and end of study assessments (EOS) visit followed by an additional post-treatment safety follow up via phone call. The total duration for each patient in the study was up to approximately 19 weeks.
Study results: In total, 42 participants (21 in the QBW251 arm and 21 in the placebo arm) completed the study, including the End of Treatment visit at Week 12.
Sputum bacterial colonization: The primary variable of the study was the change from baseline in bacterial load as measured by the number of potentially pathogenic microorganisms in sputum at week 12. Regarding the estimated treatment difference (QBW251 to placebo) from baseline to Week 12, the change in pathogenic bacterial colonization is not clinically relevant, indicating a large number of bacteria still present in sputum samples.
The most common safety findings included Bronchiectasis exacerbation, Fatigue, Pyrexia, COVID-19, Upper Respiratory Infection, Headache, Dizziness and Rhinorrhoea. The majority of AEs across the treatment groups were mild or moderate in severity.
Regarding clinical laboratory evaluation, for haematology, biochemistry and urinalysis for the different treatment groups, no clinically relevant trends were observed during the study.
Overall, QBW251 300 mg b.i.d was well tolerated and had an acceptable safety profile. although, the efficacy results need to be interpreted with caution as the study was prematurely terminated due to Novartis strategic decision to discontinue work on QBW251 clinical studies. This decision was not related to safety.
The study took place in the United Kingdom (England and Scotland), Germany, Spain, and China between April 2021 to June 2023.
Results of the study will be available on public trial registries https://www.clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/. Novartis will submit the study results to relevant regulatory authorities to obtain marketing authorization.REC name
East of Scotland Research Ethics Service REC 2
REC reference
20/ES/0118
Date of REC Opinion
22 Dec 2020
REC opinion
Further Information Favourable Opinion