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Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02555683
Recruitment Status : Completed
First Posted : September 21, 2015
Results First Posted : May 18, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

This study aimed to determine the efficacy and safety of QAW039 150 mg and QAW039 450 mg, compared with placebo, when added to GINA (Global Initiative for Asthma) steps 4 and 5 standard-of- care (SoC) asthma therapy (GINA 2016) in the following two populations:

  • patient with inadequately controlled severe asthma and high eosinophil counts at baseline (eosinophil count at Visit 1 ≥250 cells/ µl) (sub-population)
  • patients with inadequately controlled severe asthma (overall study population)

Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2016).


Condition or disease Intervention/treatment Phase
Asthma Drug: QAW039 Drug: Placebo Phase 3

Detailed Description:

This study used a randomized, multicenter, double-blind, placebo-controlled parallel-group design in which QAW039 150 mg or QA039 450 mg or placebo was added to standard of care, GINA steps 4 and 5 asthma therapy.

The study included:

  • Screening period of up to 2 weeks to assess eligibility;
  • Run-in period of approximately 2 weeks and a maximum of 6 weeks on placebo to collect baseline data for efficacy variables and compliance with the Electronic Peak Flow/ eDiary device. Upon completion of the run-in period, all patients who met the eligibility criteria were randomized to one of three treatments: QAW039 150 mg or QAW039 450 mg or placebo once daily in a ratio of 1:1:1.
  • Treatment period of 52 weeks (assessment period for all Primary and Secondary Outcome Measures). Clinic visits were scheduled approximately 4 weeks after randomization and then at approximately 8-week intervals during the active-treatment period. Phone calls occurred at specified time points between visits occurring at 8-week intervals. Patients who had successfully completed 52 weeks of treatment in this study were offered an optional participation in a safety study (CQAW039A2315).
  • Follow-up period of 4 weeks, investigational and drug-free, following the last dose of study drug. A follow-up visit occurred approximately 4 weeks (i.e., approximately 30 days) following the last dose of study therapy to complete safety assessments and pregnancy testing (if applicable). the follow-up period applied to all patients except those patients who had entered the safety study (CQAW039A2315) directly after the Week 52 study visit.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 894 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Existing Asthma Therapy in Patients With Uncontrolled Severe Asthma.
Actual Study Start Date : December 11, 2015
Actual Primary Completion Date : October 21, 2019
Actual Study Completion Date : November 4, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: QAW039 150 mg
QAW039 150 mg once daily
Drug: QAW039
QAW039 150 mg once daily

Experimental: QAW039 450 mg
QAW039 450 mg once daily
Drug: QAW039
QAW039 450 mg once daily

Placebo Comparator: Placebo
Placebo once daily
Drug: Placebo
Placebo once daily




Primary Outcome Measures :
  1. Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation [ Time Frame: Baseline, Week 52 ]
    A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

  2. Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population [ Time Frame: Baseline, Week 52 ]
    A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).


Secondary Outcome Measures :
  1. Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in High Eosinophils Subpopulation [ Time Frame: 52 weeks ]

    The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli.

    Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.


  2. Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in High Eosinophils Subpopulation [ Time Frame: Baseline, Week 52 ]
    The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

  3. Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation [ Time Frame: Baseline, Week 52 ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

  4. Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population [ Time Frame: Baseline, Week 52 ]

    The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli.

    Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life.


  5. Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in Overall Population [ Time Frame: Baseline, Week 52 ]
    The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).

  6. Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population [ Time Frame: Baseline, Week 52 ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.



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:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent and assent (if applicable).
  • Male and female patients aged ≥12 years (or ≥lower age limit allowed by health authority and/or ethics committee/institutional review board approvals).
  • A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.
  • Evidence of airway reversibility or airway hyper- reactivity.
  • FEV1 of ≤80% of the predicted normal value for patients aged ≥18 years; FEV1 of ≤90% for patients aged 12 to <18 years
  • An ACQ score ≥1.5.
  • A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.

Exclusion Criteria:

  • Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer.
  • Subjects who have participated in another trial of QAW039.
  • A QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female).
  • History of malignancy with the exception of local basal cell carcinoma of the skin.
  • Pregnant or nursing (lactating) women.
  • Serious co-morbidities.
  • Patients on greater than 20 mg of simvastatin, greater than 40 mg of atorvastatin, greater than 40 mg of pravastatin, or greater than 2 mg of pitavastatin

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): NCT02555683


Locations
Show Show 233 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] November 29, 2019
Study Protocol  [PDF] February 10, 2017

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02555683    
Other Study ID Numbers: CQAW039A2307
2015-002553-35 ( EudraCT Number )
First Posted: September 21, 2015    Key Record Dates
Results First Posted: May 18, 2020
Last Update Posted: May 18, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Asthma
QAW039
allergic asthma
allergy triggered asthma
reactive asthma
asthma attack
difficulty breathing
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Indoleacetic Acids
Plant Growth Regulators
Growth Substances
Physiological Effects of Drugs