Clinical Study to Assess the Mode of Action of QBW251 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT04268823 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CQBW251B2202
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 12

Brief Summary

The purpose of this study was to determine whether potentiating the cystic fibrosis transmembrane conductance regulator (CFTR) with QBW251 in subjects with COPD would be efficacious with regards to reducing lung and systemic inflammation and bacterial colonization as potential drivers of airway obstruction, airway destruction, remodeling and exacerbations. Furthermore, this study provided supportive data to investigate the relationship of COPD phenotype and the response in small airway structure, function, mucus load and spirometry indices as well as in improvement of overall COPD symptoms and quality of life.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Fibrinogen Plasma Concentrations After 12 Weeks of Treatment

  To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on fibrinogen. The least-squares means for change from baseline in fibrinogen plasma concentrations after 12 weeks visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM). A MMRM was fitted to the changes from baseline in fibrinogen for all time points until Day 84. A decrease in fibrinogen plasma concentration indicates improvement.

  Baseline, week 12.

Secondary Outcomes (17)

• Change From Baseline in Total Bacteria Load of log10 Colony Forming Units (CFU) After 12 Weeks of Treatment

  Baseline, week 12.

• Change From Baseline in COPD Assessment Test (CAT) Questionnaire After 12 Weeks of Treatment

  Baseline, week 12.

• Change From Baseline in Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire After 12 Weeks of Treatment

  Baseline, week 12.

• Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total and Domain Scores After 12 Weeks of Treatment

  Baseline, week 12.

• Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) After 12 Weeks of Treatment

  Baseline, week 12.

Study Arms (2)

QBW251

EXPERIMENTAL

Oral use, one capsule twice daily.

Drug: QBW251

Placebo

PLACEBO COMPARATOR

Oral use, one capsule twice daily.

Drug: Placebo

Interventions

QBW251 DRUG

Capsule 300mg

QBW251

Placebo DRUG

Capsule 300mg

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have signed an Informed Consent Form prior to initiation of any study-related procedure.
• Male and female adults aged ≥40 years at screening.
• Patients with stable COPD, stages GOLD 2-3, according to the current GOLD strategy (GOLD 2019) at screening.
• Patients with a post-bronchodilator FEV1/FVC \< 0.70 at screening
• Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and FEV1 \< 80% of the predicted normal at Screening who must have had at least 2 documented moderate or at least 1 documented severe exacerbation(s) between January 2019 to study screening.
• Patients with sputum positive (\>0 CFU) for at least one strain of potentially pathogenic microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas maltophilia, Burkholderia species, and Achromobacter species or any potential pathogenic bacteria measured by dilution/outgrowth. Any organism that is to be included and that is not included in the list of the protocol defined pathogens will be discussed case by case). Sputum samples may be re collected and re-tested once during the screening period.
• Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening.
• COPD patients are allowed to stay on macrolides as background therapy if they have bronchiectasis as a secondary diagnosis and if they are treated with them at a stable dose 3 months before screening.
• Patients with plasma fibrinogen level ≥ 320 mg/dL at screening. Fibrinogen may be re-tested once during the screening period.
• A COPD Assessment Test (CAT) score of at least 10 at screening.
• Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening.
• Patients featuring chronic bronchitis, defined as productive cough that occurs on most days (defined as \>50% of days) during at least 3 consecutive months in the year prior to screening, as assessed by documentation of patient recollection (anamnesis) or documented in patients' records.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study.

You may not qualify if:

• Patients with a history of long-QT syndrome or whose QTcF interval at screening (Fridericia method) is prolonged (QTcF \>450 ms in males, \>460 ms in females).
• Patients who have a clinically significant\* ECG abnormality before randomization. Note: Clinically significant abnormalities may include but are not limited to the following: left bundle branch block, Wolff-Parkinson-White syndrome, clinically significant arrhythmias (e.g., atrial fibrillation, ventricular tachycardia).
• Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, or hematological abnormalities, which could interfere with the assessment of the efficacy and safety of the study treatment, or patients with uncontrolled Type II diabetes.
• Patients with a history or current treatment for hepatic disease including but not limited to acute hepatitis, cirrhosis or hepatic failure.
• Patients with stable chronic hepatitis may be included in the study by agreement with Novartis Medical Expert on a case-by-case basis.
• Patients with prothrombin time international normalized ratio (PT/INR) of more than 1.5xULN at screening. Patients excluded for the PT/INR of more than 1.5xULN can be re-screened when the values have returned to normal.
• Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with a history of cancer and 5 years or more disease free survival time may be included in the study by agreement with Novartis Medical Monitor on a case-by-case basis.
• Patients who develop a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization during screening. Re-screening is permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation (i.e 2 weeks after the stop of SOC therapy for exacerbation).
• Patients who have had a respiratory tract infection within 4 weeks prior to screening. If a respiratory tract infection occurs during screening, patients can be re-screened after a minimum of 2 weeks after resolution of the respiratory tract infection.
• Patients with history of asthma or any other clinically relevant lung diseases..
• Patients with suspected active pulmonary tuberculosis or currently being treatment for active pulmonary tuberculosis.
• Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to screening suggesting low probability of recurrent active tuberculosis.
• Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung volume reductions, or lung transplantation.
• Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the trial. Participation in a maintenance program is permitted. Note: the supervised pulmonary rehabilitation program as a maintenance program has to be ongoing for at least 3 months at the time of enrollment.
• Patients with a body mass index (BMI) of more than 40 kg/m2.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Feldbach, 8330, Austria

Location

Novartis Investigative Site

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Novartis Investigative Site

Berlin, 10119, Germany

Location

Novartis Investigative Site

Berlin, 10969, Germany

Location

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Mainz, 55128, Germany

Location

Novartis Investigative Site

Witten, 58452, Germany

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

Novartis Investigative Site

London, SW3 6HP, United Kingdom

Location

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

icenticaftor

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 13, 2020
• Study Start: September 10, 2020
• Primary Completion: September 13, 2022
• Study Completion: September 20, 2022
• Last Updated: June 20, 2024
• Results First Posted: October 4, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); GB (2); AU (1); CH (3)