Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of QBW251 in Subjects With Bronchiectasis

NCT04396366 | Terminated Phase 2 Results

• 1 other identifier: CQBW251C12201
• Study Type: interventional
• Target: 42
• Locations: 4 countries
• Sites: 14

Brief Summary

The purpose of this study is to determine whether potentiating the cystic fibrosis transmembrane conductance regulator (CFTR) with QBW251 in patients with bronchiectasis will demonstrate clinical safety and efficacy related to improved mucociliary clearance with reduced bacterial colonization as potential drivers of airway obstruction, reduced airway inflammation, exacerbations and mucus load, improved lung function, clinical symptoms and quality of life to support further development in bronchiectasis.

Conditions

Bronchiectasis

Keywords

Bronchiectasis; QBW251; colony forming units

Outcome Measures

Primary Outcomes (1)

• Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12

  This measure reflects the amount of bacteria present in a patient's lungs.

  Baseline, 12 weeks

Secondary Outcomes (25)

• Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum

  Baseline, 12 weeks

• Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain)

  Baseline, Days 28, 56, 84

• Change From Baseline in Fibrinogen Plasma Concentration

  Baseline, 12 weeks

• Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol)

  Baseline, 12 weeks

• Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1)

  Baseline, Days 28, 56, 84

Study Arms (2)

QBW251 300 mg b.i.d

EXPERIMENTAL

Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks.

Drug: QBW251

Placebo

PLACEBO COMPARATOR

Participants received matching placebo, b.i.d., for 12 weeks.

Drug: Placebo

Interventions

QBW251 DRUG

QBW251, 300 mg, oral use, one capsule, twice daily.

QBW251 300 mg b.i.d

Placebo DRUG

Matching placebo, 300 mg, oral use, one capsule, twice daily.

Also known as: Comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥18 years at screening.
• Proven diagnosis of bronchiectasis by chest CT at screening as determined by investigator.
• Evidence of sputum bacterial load of ≥106 CFU/mL with at least one potentially pathogenic microorganism (H. Influenzae, M catarrhalis, S aureus, S pneumoniae, Enterobacteriaceae, P aeruginosa, Stenotrophomonous maltophilia, or any potential pathogenic non-fermenting Gram-negative bacteria measured by dilution/outgrowth).
• Documented history of at least one bronchiectasis exacerbation between January 2019 and study screening.
• Patients with bronchial hypersecretion, defined as productive cough that occurred on most days (defined as \>50% days) for at least three consecutive months within 12 months prior to screening, as assessed by documentation of patient recollection (anamnesis) or documented in patients' record.
• Patients were allowed to stay on fixed or free combinations of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS as maintenance therapy if they were treated with them at a stable dose for the last 3 months prior to screening. Patients were also allowed to stay on macrolides as maintenance therapy if they were treated with them at a stable dose, 3 months before screening. Patients were allowed to use mucolytics or hyperosmolar agents if they were treated with them before study start.
• If prescribed, patients were included in the study with unchanged chest physiotherapy for at least 4 weeks prior to screening.
• Clinically stable pulmonary status in the opinion of the investigator and unlikely to require any change in the standard regimen of care during the course of the study.

You may not qualify if:

• Patients with a history of long-QT syndrome or the QTcF interval at screening and baseline was prolonged (QTcF \> 450 ms in males, \> 460 ms in females).
• History of lung transplant or malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there was evidence of local recurrence or metastases. Patients with segmentectomy for other reasons than cancer were allowed to be included in the study. Patients with a history of cancer and 5 years or more disease free survival time might be included in the study by agreement with Novartis Medical Monitor on a case-by-case basis.
• Patients requiring long-term oxygen therapy for chronic hypoxemia. This was typically patients requiring oxygen therapy \>12 h per day delivered by home oxygen cylinder or concentrator. Note: Nocturnal oxygen therapy for transient oxygen desaturations during sleep was allowed.
• Patients with bronchiectasis who had a pulmonary exacerbation with a deterioration in three or more of the following key symptoms for at least 48 h:
• cough;
• sputum volume and/or consistency;
• sputum purulence;
• breathlessness and/or exercise tolerance;
• fatigue and/or malaise;
• hemoptysis And A clinician determined that a change in bronchiectasis treatment was required (e.g., requiring systemic glucocorticosteroid treatment and/or systemic or inhaled antibiotics) within 4 weeks prior to screening.
• In the event of an exacerbation occurring 4 weeks before screening, or between the screening and baseline (please see definition above), the participant was not to be enrolled. The participant might be rescreened once, 4 weeks after the resolution of exacerbation.
• Participants with bronchiectasis requiring therapy that might interfere with the assessment of QBW251 efficiency or who were unlikely to respond to QBW251 as follows:
• Participants with suspected active pulmonary tuberculosis or currently being treated for active pulmonary tuberculosis were not allowed. Note: Participants with a history of pulmonary tuberculosis could be enrolled if they met the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to baseline visit suggesting low probability of recurrent active tuberculosis
• Patients with active allergic bronchopulmonary aspergillosis and asthma as primary diagnosis.
• Patients with cystic fibrosis

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Innovative Medicines Initiative: collaborator

Study Sites (14)

Novartis Investigative Site

Guangzhou, Guangdong, 510120, China

Location

Novartis Investigative Site

Shanghai, 200433, China

Location

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Mainz, 55128, Germany

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Girona, Catalonia, 17007, Spain

Location

Novartis Investigative Site

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

Cambridge, CB2 0AY, United Kingdom

Location

Novartis Investigative Site

Edinburgh, EH10 5HF, United Kingdom

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Novartis Investigative Site

Liverpool, L9 7AL, United Kingdom

Location

Novartis Investigative Site

London, SW3 6PH, United Kingdom

Location

Novartis Investigative Site

Manchester, M23 9LT, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Bronchiectasis

Interventions

icenticaftor

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 20, 2020
• Study Start: February 2, 2021
• Primary Completion: June 15, 2023
• Study Completion: June 21, 2023
• Last Updated: September 26, 2025
• Results First Posted: March 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); DE (3); CN (2); GB (7)