Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02571777
• Date of registration: 05/10/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma
• Scientific title: A Multicenter, Randomized, 52-week, Double-blind, Parallelgroup, Active Controlled Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma
• Date of first enrolment: December 8, 2015
• Target sample size: 3092
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02571777
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, China, Colombia, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Jordan, Latvia, Lebanon, Lithuania, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, United Kingdom, Vietnam

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with a diagnosis of asthma, (GINA 2015) for a period of at least 1 year prior
to Visit 1 (Screening).

- Patients who have used medium or high dose of ICS/LABA combinations for asthma for at
least 3 months and at stable medium or high doses of ICS/LABA for at least 1 month
prior to Visit 1.

- Patients must be symptomatic at screening despite treatment with mid or high stable
doses of ICS/LABA. Patients with ACQ-7 score = 1.5 at Visit 101 and at Visit 102
(before randomization).

- Patients with documented history of at least one asthma exacerbation which required
medical care from a physician, ER visit (or local equivalent structure) or
hospitalization in the 12 months prior to Visit 1, and required systemic
corticosteroid treatment.

- Pre-bronchodilator FEV1 of < 80 % of the predicted normal value for the patient
according to ATS/ERS guidelines after withholding bronchodilators at both visits 101
and 102.

- Withholding period of bronchodilators prior to spirometry: SABA for = 6 hrs, Twice
daily LABA (or FDC of ICS/LABA) for = 12 hrs, Once daily LABA (or FDC of ICS/LABA) for
= 24 hrs, SAMA for = 8 hrs, Short acting xanthines for 12 hrs, Long acting xanthines
for 24 hrs, .

- Washout period of each drug should be kept as close as possible as above and should
not be longer. If longer washout period is needed due to scheduling issues, please
contact Novartis Medical monitor.

- A one-time repeat of percentage predicated FEV1 (Pre-bronchodilator) at Visit 101
and/or Visit 102 is allowed in an ad-hoc visit. Repeat of Visit 101 spirometry should
be done in an ad-hoc visit to be scheduled on a date that would provide sufficient
time to receive confirmation from the spirometry data central reviewer of the validity
of the assessment before randomization. Run-in medication should be dispensed once
spirometry assessment met inclusion criteria (ATS/ERS quality criteria, FEV1 %
predicted normal value, and reversibility) as per equipment

- A one-time rescreen is allowed in case the patient fails to meet the criteria at the
repeat, provided the patient returned to the required treatment as per inclusion
criteria 4

- Patients who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after
administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit
101.All patients must perform a reversibility test at Visit 101. If reversibility is
not demonstrated at Visit 101 then one of the following criteria need to be met.

- Reversibility should be repeated once.

- Patients may be permitted to enter the study with historical evidence of reversibility
that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1.

- Alternatively, patients may be permitted to enter the study with a historical positive
bronchoprovocation test that was performed within 2 years prior to Visit 1. If
reversibility is not demonstrated at Visit 101 (or after repeated assessment in an
ad-hoc visit) and historical evidence of reversibility/bronchoprovocation is not
available (or was not performed according to the ATS/ERS guidelines patients must be
screen failed

- Spacer devices are permitted during reversibility testing only. The Investigator or
delegate may decide whether or not to use a spacer for the reversibility testing

Exclusion Criteria:

- Patients who have had an asthma attack/exacerbation requiring systemic steroids or
hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening). If
patients experience an asthma attack/exacerbation requiring systemic steroids or
hospitalization or emergency room visit between Visit 1 and Visit 102 they may be
re-screened 6 weeks after recovery from the exacerbation.

- Patients who have ever required intubation for a severe asthma attack/exacerbation.

- Patients who have a clinical condition which is likely to be worsened by ICS
administration (e.g. glaucoma, cataract and fragility fractures) who are according to
investigator's medical judgment at risk participating in the study.

- Patients treated with a LAMA for asthma within 3 months prior Visit 1 (Screening).

- Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or
bladder-neck obstruction or severe renal impairment or urinary retention. BPH patients
who are stable on treatment can be considered).

- Patients who have had a respiratory tract infection or asthma worsening as determined
by investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and
Visit 102. Patients may be re-screened 4 weeks after recovery from their respiratory
tract infection or asthma worsening.

- Patients with evidence upon visual inspection (laboratory culture is not required) of
clinically significant (in the opinion of investigator) oropharyngeal candidiasis at
Visit 102 or earlier, with or without treatment. Patients may be re-screened once
their candidiasis has been treated and has resolved.

- Patients with any chronic conditions affecting the upper respiratory tract (e.g.
chronic sinusitis) which in the opinion of the investigator may interfere with the
study evaluation or optimal participation in the study.

- Patients with a history of chronic lung diseases other than asthma, including (but not
limited to) chronic obstructive pulmonary disease, sarcoidosis, interstitial lung
disease, cystic fibrosis, clinically significant bronchiectasis and active
tuberculosis.

- Patients with Type I diabetes or uncontrolled Type II diabetes.

- Patients who, either in the judgment of the investigator or the responsible Novartis
personnel, have a clinically significant condition such as (but not limited to)
unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left
ventricular failure arrhythmia, uncontrolled hypertension, cerebrovascular disease,
psychiatric disease, neurodegenerative diseases, or other neurological disease,
uncontrolled hypo- and hyperthyroidism and other autoimmune diseases, hypokalemia,
hyperadrenergic state, or ophthalmologic disorder or patients with a medical condition
that might compromise patient safety or compliance, interfere with evaluation, or
preclude completion of the study.

- Patients with paroxysmal (e.g., intermittent) atrial fibrillation are excluded.
Patients with persistent atrial fibrillation as defined by continuous atrial
fibrillation for at least 6 months a


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Drug: salmeterol/fluticasone

Drug: QVM149 150/50/160

Drug: QVM149 150/50/80

Drug: QMF149 150/160

Drug: QMF149 150/320

Primary Outcome(s)

Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus QMF149 at Week 26 [Time Frame: 26 weeks]

Secondary Outcome(s)

Annual Rate of Asthma Exacerbations by Exacerbation Category [Time Frame: 52 weeks]

Trough FEV1 at Week 52 [Time Frame: 52 weeks]

Trough Forced Expiratory Flow (FEF) Between 25% and 75% of FVC (FEF25-75) at 52 Weeks [Time Frame: Up to Week 52]

Change From Baseline in Percentage of Nights With no Night-time Awakenings Over 52 Weeks [Time Frame: Baseline, 52 weeks]

Duration in Days of Asthma Exacerbations by Exacerbation Category [Time Frame: Up to Week 52]

Pre-dose Forced Vital Capacity (FVC) at Week 4 and Week 12 [Time Frame: 4 weeks, 12 weeks]

Change From Baseline in Percentage of Days With no Daytime Symptoms Over 52 Weeks [Time Frame: Baseline, 52 weeks]

Time to First Asthma Exacerbation by Exacerbation Category [Time Frame: 52 weeks on average, up to 416 days]

Asthma Control Questionnaire (ACQ-7) at Week 26 and Week 52 [Time Frame: 26 weeks, 52 weeks]

Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment [Time Frame: Baseline, 26 weeks, 52 weeks]

Change From Baseline in Percentage of Mornings With no Symptoms on Rising Over 52 Weeks [Time Frame: Baseline, 52 weeks]

Change From Baseline in Percentage of Rescue Medication Free Days Over 26 and 52 Weeks [Time Frame: Baseline, 26 weeks, 52 weeks]

Percentage of Patients Achieving the Minimal Clinically Important Difference (MCID) ACQ = 0.5 at Week 26 and Week 52 [Time Frame: 26 weeks, 52 weeks]

Pre-dose FEV1 at Weeks 4 and 12 [Time Frame: 4 weeks, 12 weeks]

Time to First Hospitalization for Asthma Exacerbation [Time Frame: 52 weeks on average, up to 416 days]

Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus Salmeterol/Fluticasone at Week 26 [Time Frame: 26 weeks]

Change From Baseline in Percentage of Asthma Symptom-free Days Over 52 Weeks [Time Frame: Baseline, 52 weeks]

Change From Baseline in Percentage of Days Without Rescue Medication Use Over 26 and 52 Weeks [Time Frame: Baseline, 26 weeks, 52 weeks]

Asthma Quality of Life Questionnaire (AQLQ) at Week 52 [Time Frame: 52 weeks]

Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category [Time Frame: Up to Week 52]

Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes [Time Frame: Up to Week 52]

Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbation [Time Frame: 52 weeks on average, up to 416 days]

Total Amount of Oral Corticosteroid Used (in Prednisone-equivalent mg Doses) to Treat Asthma Exacerbations [Time Frame: Up to Week 52]

Secondary ID(s)

2015-002899-25

CQVM149B2302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02571777