A Long-term Safety Study of QVM149 in Japanese Patients With Asthma

• ClinicalTrials.gov Identifier: NCT03100825
• Recruitment Status: Completed
• First Posted: April 4, 2017
• Results First Posted: April 7, 2020
• Last Update Posted: April 7, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this study is to provide long term safety data of QVM149 in Japanese patients with asthma for the registration of QVM149 in Japan.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: QVM149	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Single Arm, 52-week Treatment Study to Assess the Safety of QVM149 in Japanese Patients With Asthma
• Actual Study Start Date: April 28, 2017
• Actual Primary Completion Date: September 18, 2018
• Actual Study Completion Date: April 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: QVM149; All eligible patients take QVM149 150/50/160 μg once daily over 52 weeks.	Drug: QVM149; QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate); Other Name: QVM149 150/50/160 μg once daily, delivered as powder in hard capsules via Concept1 inhaler

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) [ Time Frame: Up to 52 Weeks ]
   An adverse event (AE) was any untoward medical occurrence (example; any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study until the end of study visit. TEAEs were defined as adverse events started on or after the time of the first inhalation of study drug but no later than 7 days after the last administration (30 days in the case of SAEs). SAE was defined as any adverse event (appearance of [or worsening of any pre-existing]) undesirable sign, symptom or medical conditions which is fatal or life-threatening or results in persistent or significant disability/incapacity or constitutes a congenital anomaly/birth defect or requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.

Secondary Outcome Measures :

1. Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52 [ Time Frame: Baseline (Pre-dose), Week 26, Week 52 ]
   FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Change from baseline in FEV1 at week 26 and 52 was reported.
2. Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52 [ Time Frame: Baseline (Pre-dose), Week 26, Week 52 ]
   Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. Change from baseline in FVC at week 26 and 52 was reported.
3. Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks [ Time Frame: Baseline up to week 52 ]
   PEF is the peak expiratory flow, the maximum speed of expiration. Electronic peak flow meter (ePEF) was given to each participant at visit 1 for the measurement of morning and evening PEF. Change from baseline in morning and evening PEF over 52 weeks was measured.
4. Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52 [ Time Frame: Baseline, Week 26, Week 52 ]
   ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point Likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. The questions were equally weighted and the total score is the mean of the 7 items. A decrease of ACQ-7 score of at least 0.5 from baseline was considered to be clinically meaningful improvement.
5. Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52 [ Time Frame: Week 26, Week 52 ]
   ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. Questions were equally weighted and total score is mean of 7 items. A decrease from baseline of at least 0.5 units in ACQ-7 score was considered to be clinically meaningful improvement. The proportion of participants achieving the clinically meaningful improvement threshold in ACQ-7 score were reported at Week 26 and Week 52.
6. Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks [ Time Frame: Baseline up to week 52 ]
   Daily use of rescue medication (number of puffs taken in the previous 12 hours) were recorded each morning and evening throughout the 52 week treatment by the participant using their electronic diary.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Male and female adult patient ≥ 18 years old.
• Patients with a diagnosis of persistent asthma (GINA 2016) for a period of at least 1 year prior to Visit 1.
• Patients who have used medium or high dose of ICS/LABA combinations for asthma for at least 3 months and at stable dose and regimen for at least 4 weeks prior to Visit 1.
• An ACQ-7 score ≥ 1.5 at Visits 2.

• Pre-bronchodilator FEV1 of ≥ 40% and ≤ 85% of the predicted normal value for the patient after withholding bronchodilators at Visit 2.

  o Repeating is allowed once only. Repeating of percentage predicted FEV1 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 Visit 99.

• Patients must demonstrate reversibility defined as an increase in FEV1 of ≥ 12% and 200 mL within 15 to 30 minutes after administration of 400 µg of salbutamol at Visit 2. 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.

  • If reversibility is not proven at Visit 2, patients may be permitted to enter the study with historical evidence of reversibility that was performed within 5 years prior to Visit 1.
  • Alternatively, patients may be permitted to enter the study with a historical positive bronchoprovocation test (defined as a provoked fall in FEV1 of 20% by bronchoconstriction agent e.g., methacholine, histamine) or equivalent test (e.g., astography) that was performed within 5 years prior to Visit 1.
  • If reversibility is not proven at Visit 2 and historical data is not available, reversibility should be repeated once in an ad-hoc visit scheduled as close as possible from the first attempt (but not on the same day).

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.
• 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 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 or between Visit 1 and Visit 99. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
• Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
• Patients with severe narcolepsy and/or insomnia
• Pregnant or nursing (lactating) women
• Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 30 days after stopping of investigational medication

Contacts and Locations

Locations

Japan

Novartis Investigative Site

Koga city, Fukuoka, Japan, 811 3195

Novartis Investigative Site

Yanagawa-city, Fukuoka, Japan, 832-0059

Novartis Investigative Site

Maebashi-shi, Gunma, Japan, 371-0054

Novartis Investigative Site

Hiroshima-city, Hiroshima, Japan, 732-0052

Novartis Investigative Site

Sapporo-city, Hokkaido, Japan, 001-0901

Novartis Investigative Site

Tomakomai-city, Hokkaido, Japan, 053-8506

Novartis Investigative Site

Takamatsu-city, Kagawa, Japan, 761-8073

Novartis Investigative Site

Fujisawa-city, Kanagawa, Japan, 251-0041

Novartis Investigative Site

Sagamihara-city, Kanagawa, Japan, 228-8522

Novartis Investigative Site

Sagamihara-city, Kanagawa, Japan, 229-1103

Novartis Investigative Site

Yokohama-city, Kanagawa, Japan, 236 0051

Novartis Investigative Site

Yokkaichi-city, Mie, Japan, 510-8561

Novartis Investigative Site

Nagaoka-City, Niigata, Japan, 940-2085

Novartis Investigative Site

Osaka city, Osaka, Japan, 530 0001

Novartis Investigative Site

Sakai-city, Osaka, Japan, 591 8037

Novartis Investigative Site

Ageo-city, Saitama, Japan, 362-8588

Novartis Investigative Site

Chuo ku, Tokyo, Japan, 104-0031

Novartis Investigative Site

Chuo-ku, Tokyo, Japan, 103-0003

Novartis Investigative Site

Chuo-ku, Tokyo, Japan, 103-0027

Novartis Investigative Site

Chuo-ku, Tokyo, Japan, 103-0028

Novartis Investigative Site

Ota-ku, Tokyo, Japan, 145 0063

Novartis Investigative Site

Setagaya-ku, Tokyo, Japan, 158-0097

Novartis Investigative Site

Setagaya-ku, Tokyo, Japan, 158-8531

Novartis Investigative Site

Shinagawa-ku, Tokyo, Japan, 142-8666

Novartis Investigative Site

Toshima ku, Tokyo, Japan, 170 0003

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] April 6, 2017

Statistical Analysis Plan  [PDF] April 6, 2017

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03100825
• Other Study ID Numbers: CQVM149B1304
• First Posted: April 4, 2017
• Results First Posted: April 7, 2020
• Last Update Posted: April 7, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

QVM149; Asthma; Japanese; Allergic asthma; Allergy triggered asthma; Reactive asthma; Asthma attack; Difficulty breathing

Additional relevant MeSH terms:

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