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Trial record 1 of 7 for:    QVM149
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Investigating the Effects of QVM149 on MRI Ventilation Defects (XPERTT)

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ClinicalTrials.gov Identifier: NCT04206761
Recruitment Status : Not yet recruiting
First Posted : December 20, 2019
Last Update Posted : January 20, 2020
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Dr. Grace Parraga, Western University, Canada

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: QVM149 Drug: High Dose Dual Therapy (ICS/LABA) Phase 3

Detailed Description:

A single site, two arm, randomized, open-label study in participants with asthma, who demonstrate visually obvious ventilation defects despite being on ICS/LABA was chosen to evaluate the capability of QVM149 150/50/160 μg once daily as compared to high dose dual therapy (ICS/LABA) to improve ventilation heterogeneity. According to the design of the study, hyperpolarized Xenon-129 (129Xe) will be used to measure ventilation defects in asthma participants as ventilation defect percent (VDP). A low-dose chest CT acquired within a few minutes of MRI will provide a way to measure both airway and parenchymal abnormalities. The selection of the QVM149 150/50/160 μg was made in order to keep the ICS dose equipotent to baseline therapy and to the active comparator arm and to directly compare the addition of a long-acting muscarinic antagonist (LAMA) versus continuing the therapy with high dose dual therapy (ICS/LABA).

This study will be a single site, two arm, randomized, open-label study with the following treatment:

  • Treatment A: 2-week treatment with Indacaterol/Glycopyrronium/Mometasone 150/50/160 μg delivered as powder in hard capsules via Breezhaler, a breath-activated device which will deliver a specific dose of medication.
  • Treatment B: 2-week treatment with high dose dual therapy (ICS/LABA) in any approved drug formulation and delivery device. (Continue receiving high dose ICS/LABA therapy at the same dose and in the same formulation as at baseline).

The study will consist of a screening/inclusion period of 1-5 days, followed by a treatment period of 14 days. The evaluation team including MRI observers will be blinded to treatment.

At Visit 101, informed consent will be obtained before any study related assessments or procedures are performed. Asthma medications and eligibility criteria will be reviewed. Furthermore, at Visit 101, safety assessments including electrocardiography (ECG), hematology, blood chemistry, urinalysis, and spirometry to test reversibility will be performed. Once the above criteria are met, participants will move on to Visit 102.

At Visit 102 all additional assessments, including MRI to detect visually obvious ventilation defects, low-dose chest CT, and Pulmonary Function Test assessments including spirometry, plethysmography, Lung Clearance Index (LCI) and Forced Oscillation Technique (FOT) will be conducted. Participants who qualify will then be randomized and entered into the 14 days treatment period and continue with the assessments according to study protocol. Participants will be supplied with open-label Indacaterol/Glycopyrronium/ Mometasone 150/50/160 μg o.d. delivered as powder in hard capsules via Breezhaler or continue with their previously prescribed high dose dual therapy (ICS/LABA) in any approved drug formulation and delivery device, which will be used during the study treatment period and stopped at Visit 201.

Upon completion of the study treatment period at Visit 201, all participants will undergo post-treatment assessments, including MRI, pre- and post-salbutamol pulmonary function testing including spirometry, plethysmography, LCI, FOT, and asthma questionnaires.

A final visit, Visit 301 will be scheduled for safety assessments. All participants will undergo vital signs, spirometry, ECG, bloodwork and urinalysis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A single site, two arm, randomized, open-label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Xenon MRI Probing vEntilation Response to Triple Therapy (QVM149)
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment - QVM149
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
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
Other Name: indacaterol acetate/glycopyrronium bromide/mometasone furoate

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




Primary Outcome Measures :
  1. 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 [ Time Frame: Day 0 and 14 ]
    Change in VDP

  2. 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) [ Time Frame: Day 0 and 14 ]
    Difference in change in VDP


Secondary Outcome Measures :
  1. Explore univariate correlation and linear regression of MRI ventilation defect percent and forced expiration volume in one second. [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and forced expiration volume in one second will be assessed using univariate correlation analysis and linear regression. This information gives insight into the relationship between pulmonary function and structure.

  2. Explore univariate correlation and linear regression of MRI ventilation defect percent and forced vital capacity [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and forced vital capacity will be assessed using univariate correlation analysis and linear regression. This information gives insight into the relationship between pulmonary function and structure.

  3. Explore univariate correlation and linear regression of MRI ventilation defect percent and lung volumes [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and lung volumes will be assessed using univariate correlation analysis and linear regression. This information gives insight into the relationship between pulmonary function and structure.

  4. Explore univariate correlation and linear regression of MRI ventilation defect percent and forced oscillation technique [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and forced oscillation technique will be assessed using univariate correlation analysis and linear regression. This information gives insight into the relationship between pulmonary function, structure and inflammation.

  5. Explore univariate correlation and linear regression of MRI ventilation defect percent and lung clearance index [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and lung clearance index will be assessed using univariate correlation analysis and linear regression. This information gives insight into the relationship between pulmonary function and structure.

  6. Explore univariate correlation and linear regression of MRI ventilation defect percent and asthma control as measured by the Asthma Control Questionnaire [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and asthma control, as measured by the Asthma Control Questionnaire (ACQ-6) will be assessed using a univariate correlation analysis and linear regression. The ACQ-6 is scored from 0 to 6, with higher scores indicating more uncontrolled asthma.

  7. Explore univariate correlation and linear regression of MRI ventilation defect percent and asthma-related quality of life as measured by the Asthma Quality of Life Questionnaire [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and asthma-related quality of life as measured by the Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) will be assessed using a univariate correlation analysis and linear regression. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.

  8. Explore univariate correlation and linear regression of MRI ventilation defect percent and daily life and perceived well-being as measured by the St. George's Respiratory Questionnaire [ Time Frame: Day 14 ]
    The relationship between ventilation defect percent and daily life and perceived well-being as measured by the St. George's Respiratory Questionnaire (SGRQ) will be assessed using univariate correlation analysis and linear regression. The SGRQ is scored from 0-100 with higher scores indicating more limitations.

  9. Change from baseline forced expiration volume in one second [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  10. Difference in change from baseline forced expiration volume in one second after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  11. Change from baseline forced vital capacity [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  12. Difference in change from baseline forced vital capacity after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  13. Change from baseline residual volume. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  14. Difference in change from baseline residual volume after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  15. Change from baseline total lung capacity. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  16. Difference in change from baseline total lung capacity after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  17. Change from baseline forced oscillation technique [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function and inflammation

  18. Difference in change from baseline forced oscillation technique after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function and inflammation

  19. Change from baseline lung clearance index [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  20. Difference in change from baseline lung clearance index after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Indicator of pulmonary function

  21. Change from baseline in asthma control [ Time Frame: Day 0 and 14 ]
    Asthma Control Questionnaire (ACQ-6) is used to evaluate asthma control. The ACQ-6 is scored from 0 to 6, with higher scores indicating more severely uncontrolled asthma.

  22. Difference in change from baseline in asthma control after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Asthma Control Questionnaire (ACQ-6) is used to evaluate asthma control. The ACQ-6 is scored from 0 to 6, with higher scores indicating more severely uncontrolled asthma.

  23. Change from baseline in asthma-related quality of life [ Time Frame: Day 0 and 14 ]
    Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) evaluates asthma-related quality of life. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.

  24. Difference in change from baseline in asthma-related quality of life after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) evaluates asthma-related quality of life. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.

  25. Change from baseline in daily life and perceived well-being as measured by the St. George's Respiratory Questionnaire [ Time Frame: Day 0 and 14 ]
    Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) evaluates asthma-related quality of life. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.

  26. Difference in change from baseline in daily life and perceived well-being as measured by the St. George's Respiratory Questionnaire after use of QVM149 compared to high dose dual therapy. [ Time Frame: Day 0 and 14 ]
    Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) evaluates asthma-related quality of life. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 :

    1. 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
    2. Documented increase in FEV1 of ≥ 12% and 200 ml 15 to 30 minutes after administration of 400μg salbutamol in past 24 months
    3. Documented increase in FEV1 of ≥ 12% and 200 ml after treatment for asthma (e.g. treatment with ICS) in past 24 months
    4. 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.

Exclusion Criteria:

  • 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 paroxysmal (e.g., intermittent) atrial fibrillation are excluded. Participants with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blockers, calcium channel blocker, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such participants, atrial fibrillation must be present at Visit 101 with a resting ventricular rate < 100/min.
  • 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.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and follow-up period. Highly effective contraception methods include:

    1. True sexual abstinence with male partner(s) (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.
    2. Female sterilization (have had surgical tubal ligation, bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
    3. Vasectomized male partner(s) (at least 6 months prior to Visit 101).
    4. Use hormonal contraception with failure rate <1% (e.g. oral contraceptive pill, Depo-Provera™ injections, Erva Patch™ or Nuvaring™).
    5. Placement of an MRI safe intrauterine device (IUD) or intrauterine system (IUS).

In case of use of hormonal contraception, women should have been stable on the same pharmacological agent for a minimum of 3 months before Visit 101. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04206761


Contacts
Layout table for location contacts
Contact: Grace E Parraga, PhD 519-931-5265 gparraga@robarts.ca
Contact: Danielle Knipping, RN 519-931-5777 ext 24197 dknipping@robarts.ca

Locations
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Canada, Ontario
Robarts Research Insitute; The University of Western Ontario; London Health Sciences Centre
London, Ontario, Canada, N6A 5B7
Contact: Grace E Parraga, PhD    519-931-5265    gparraga@robarts.ca   
Sponsors and Collaborators
Dr. Grace Parraga
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Grace E Parraga, PhD Robarts Research Institute, The University of Western Ontario

Layout table for additonal information
Responsible Party: Dr. Grace Parraga, Professor, Western University, Canada
ClinicalTrials.gov Identifier: NCT04206761    
Other Study ID Numbers: ROB0045
First Posted: December 20, 2019    Key Record Dates
Last Update Posted: January 20, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Grace Parraga, Western University, Canada:
QVM149
Indacaterol
Glycopyrronium
Mometasone
Xenon
Triple Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Mometasone Furoate
Glycopyrrolate
Bromides
Anticonvulsants
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs