Investigating the Effects of QVM149 on MRI Ventilation Defects

NCT04206761 | Withdrawn Phase 3

• 1 other identifier: ROB0045
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare treatment with QVM149, an inhaler that contains three types of asthma medications compared to an inhaler that contains two types of asthma medications. Both inhalers contain an inhaled corticosteroid, which reduces inflammation in the lungs, and a medication that helps to open up the airways. The investigational inhaler, QVM149, contains a third medication that also works to open up the airways. The investigators will measure the difference in these two treatments with magnetic resonance imaging (MRI) using a special technique using xenon gas to show how gas spreads in the lungs. In healthy lungs, the gas fills the lungs evenly, but in unhealthy lungs, the gas may fill the lungs unevenly and they will appear patchy. The patchy areas are called ventilation defects. A CT of the chest will be done to assess the structure of the lungs. The investigators will also use lung function testing and questionnaires to evaluate the differences between these therapies.

Conditions

Asthma

Keywords

QVM149; Indacaterol; Glycopyrronium; Mometasone; Xenon; Triple Therapy

Outcome Measures

Primary Outcomes (2)

• Change from baseline airway function measured using 129-Xenon MRI ventilation defect percent at the end of 2 weeks of treatment with QVM149 150/50/160 μg once daily

  Change in VDP

  Day 0 and 14

• Difference in change from baseline airway function measured using 129-Xenon MRI ventilation defect percent after 2 weeks use of QVM149 150/50/160 μg once daily compared to high dose dual therapy (ICS/LABA)

  Difference in change in VDP

  Day 0 and 14

Secondary Outcomes (26)

• Explore univariate correlation and linear regression of MRI ventilation defect percent and forced expiration volume in one second.

  Day 14

• Explore univariate correlation and linear regression of MRI ventilation defect percent and forced vital capacity

  Day 14

• Explore univariate correlation and linear regression of MRI ventilation defect percent and lung volumes

  Day 14

• Explore univariate correlation and linear regression of MRI ventilation defect percent and forced oscillation technique

  Day 14

• Explore univariate correlation and linear regression of MRI ventilation defect percent and lung clearance index

  Day 14

Study Arms (2)

Treatment - QVM149

EXPERIMENTAL

Participants will complete a two week treatment with QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) 150/50/160 μg delivered as powder in hard capsules via Breezhaler, a breath-activated device which will deliver a specific dose of medication via inhalation.

Drug: QVM149

Control

ACTIVE COMPARATOR

Participants will continue their clinically prescribed treatment with a high dose dual therapy of Inhaled Corticosteroid (ICS)/Long-Acting Beta2-Agonist (LABA) in any approved drug formulation and delivery device for the treatment period of two weeks. (Participants will continue receiving high dose ICS/LABA therapy at the same dose and in the same formulation as at baseline).

Drug: High Dose Dual Therapy (ICS/LABA)

Interventions

QVM149 DRUG

QVM149 is an investigational drug consisting of 150μg indacaterol acetate, 50μg glycopyrronium bromide and 160μg mometasone furoate. The drug is delivered as powder in hard capsules via Breezhaler, a breath-activated device which will deliver a specific dose of medication

Also known as: indacaterol acetate/glycopyrronium bromide/mometasone furoate

Treatment - QVM149

High Dose Dual Therapy (ICS/LABA) DRUG

High dose inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) in any approved drug formulation and delivery device.

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be directly obtained from legally competent participants before any study- related assessment is performed.
• Male and female adult participant ≥ 18 years of age and ≤ 80 years of age.
• Participants with a confirmed clinical diagnosis of asthma by a respirologist for a period of at least 6 months prior to Visit 101.
• Participants who demonstrate reversibility in FEV1 by one of :
• Increase in forced expiratory volume in one second (FEV1) of ≥ 12% and 200 ml 15 to 30 minutes after administration of 400μg salbutamol at Visit 101
• Documented increase in FEV1 of ≥ 12% and 200 ml 15 to 30 minutes after administration of 400μg salbutamol in past 24 months
• Documented increase in FEV1 of ≥ 12% and 200 ml after treatment for asthma (e.g. treatment with ICS) in past 24 months
• Documented positive methacholine challenge in past 24 months
• Participants who have used high dose dual therapy (ICS/LABA) for asthma for at least 3 months and at a stable dose equivalent to high dose ICS for at least 1 month prior to Visit 101 (please refer to Table 1-1 for ICS dosages).
• Participants with visually obvious MRI ventilation defects at Visit 102.
• Pre-bronchodilator FEV1 of \< 85% of the predicted normal value for the participant after withholding bronchodilators prior to spirometry at Visit 101.

You may not qualify if:

• Participants meeting contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia.
• Currently smoking or vaping any substance (e.g. nicotine, cannabis) at Visit 101 or within 12 months of visit 101.
• Ex-smoker of nicotine or cannabis with a smoking history of ≥ 10 pack years or 20 joint years (Note: 1 pack is equivalent to 20 cigarettes. 10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs. 1 joint year is equivalent to 1 joint/day x 1 year)
• Participants diagnosed with Chronic Obstructive Pulmonary Disease (COPD). Diagnoses of asthma- COPD overlap syndrome may be eligible.
• Participants who have had an asthma attack/exacerbation requiring systemic steroids, hospitalization and/or emergency room visit within 6 weeks of Visit 101 or a respiratory tract infection requiring antibiotics within 4 weeks prior to Visit 101. If participants experience an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit between Visit 101 and Visit 201, they will be withdrawn from the study but may be re-screened 4 weeks after recovery from the exacerbation.
• Participants treated with a LAMA for asthma within 3 months prior to Visit 101.
• Participants with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder- neck obstruction or severe renal impairment or urinary retention. BPH participants who are stable on treatment can be considered.
• Participants with a history of chronic lung diseases other than asthma, including (but not limited to) sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
• Use of other investigational drugs within 30 days (e.g. small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer.
• History of hypersensitivity to any of the study treatments or its excipients or to other drugs of similar chemical classes.
• Participants with a history of myocardial infarction within 12 months prior to Visit 101.
• Concomitant use of agents known to prolong the QT interval unless it can be discontinued for the duration of study. Decisions about the discontinuation of such agents will be made between the Qualified Investigator and participant.
• Participants with a history of long QT syndrome or whose QTc measured at Visit 101 (Fridericia method) is prolonged (\> 450 msec for males and \> 460 msec for females). These participants may not be rescreened.
• Participants with a history of lactose intolerance and hypersensitivity to any of the study drugs or its excipients, or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

Sponsors & Collaborators

• Dr. Grace Parraga: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Robarts Research Insitute; The University of Western Ontario; London Health Sciences Centre

London, Ontario, N6A 5B7, Canada

Location

MeSH Terms

Conditions

Asthma

Interventions

indacaterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Grace E Parraga, PhD

  Robarts Research Institute, The University of Western Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: A single site, two arm, randomized, open-label study

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 20, 2019
• Study Start: December 1, 2021
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 14, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)