A Long-term Safety Study of QMF149 in Japanese Participants With Asthma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03100500
• Collaborator: (none)
• Enrollment: 51
• Locations: 15
• Arm: 1
• Actual Duration (Months): 21.6
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to provide long term safety data of QMF149 in Japanese participants with inadequately controlled asthma for the registration of QMF149 in Japan.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QMF149	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• 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 QMF149 in Japanese Patients With Asthma
• Actual Study Start Date: Apr 25, 2017
• Actual Primary Completion Date: Jul 19, 2018
• Actual Study Completion Date: Feb 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QMF149 All eligible patients take QMF149 150/320 μg once daily over 52 weeks.	Drug: QMF149; QMF149 150/320 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) and Serious Adverse Events (SAEs) [Up to 52 weeks]

   A TEAE is any adverse event that started on or after the time of the first inhalation of study drug but not later than 7 days (30 days in the case of a SAE) after the last administration. A SAE is described as any adverse event that leads to death, is life-threatening, results in persistent or significant disability/incapacity, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event which is medically significant.

Secondary Outcome Measures

1. Change From Baseline of Pre-Dose Forced Expiratory Volume in 1 Second (FEV1) Measured After 26 And 52 Weeks Treatment [Baseline, Weeks 26 and 52]

   The pre-dose FEV1 was defined as the mean of the pre-dose 45 and 15 min FEV1 values prior to evening dose. 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. A positive change from baseline in FEV1 indicates improvement in lung function.

2. Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment [Baseline up to Week 52]

   PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. PEF was analyzed separately in the morning and evening using an electronic Peak Flow Meter (ePEF). A positive change from baseline in PEF indicates improvement in lung function.

3. Change From Baseline of Asthma Control Questionnaire (ACQ-7) After 26 And 52 Weeks Treatment [Baseline, Weeks 26 and 52]

   The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question (question 7) was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.

4. Responder Rate of Participants Achieving the Minimal Important Difference (MID) of ACQ-7 ≥ 0.5 After 26 And 52 Weeks Treatment [Weeks 26 and 52]

   The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question (question 7) was completed by the study investigator using data from the Master Scope spirometer. The proportion of participants who achieved an improvement of at least 0.5 in ACQ-7 (i.e. decrease of ACQ-7 score of at least 0.5 from baseline) at post-baseline visits were analyzed.

5. Change From Baseline of Rescue Medication Use During 52 Weeks Treatment [Baseline up to Week 52]

   Based on the electronic-diary data, the total number of puffs of rescue medication per day over the 52 weeks were calculated and divided by the total number of days to derive the mean daily number of puffs of rescue medication taken for the participant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 for a period of at least 1 year prior to Visit 1.

• Patients who have used medium or high dose inhaled corticosteroids (ICS) plus at least 1 controller for asthma for at least 3 months and at stable dose and regimen for at least 4 weeks prior to Visit 1.

• Patients must have Asthma Control Questionnaire-7 (ACQ-7) score ≥ 1.5 at Visits 2 and qualify for treatment with high dose ICS/long-acting β2 agonist (LABA).

• Pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) of ≥ 50% and ≤ 85% of the predicted normal value for the patient after withholding bronchodilators at Visit

• 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

1. 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.

• Where patient is assessed as eligible based on historical evidence, a copy of the original printed report must be available as source documentation.

• 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).

• If reversibility is not demonstrated at Visit 2 (or after repeated assessment at ad-hoc visit) and historical evidence of reversibility/bronchoprovocation/astography is not available, patients must be screen failed.

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 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) chronic obstructive pulmonary disease, 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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nagoya	Aichi	Japan	457-8511
2	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	819-8555
3	Novartis Investigative Site	Chitose-city	Hokkaido	Japan	066-0021
4	Novartis Investigative Site	Kitahiroshima	Hokkaido	Japan	061-1121
5	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	006-0811
6	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	064-0801
7	Novartis Investigative Site	Takamatsu-city	Kagawa	Japan	760-0018
8	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	223-0059
9	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	231-8682
10	Novartis Investigative Site	Yokosuka	Kanagawa	Japan	239-0821
11	Novartis Investigative Site	Chino-city	Nagano	Japan	391-0011
12	Novartis Investigative Site	Higashiosaka-city	Osaka	Japan	577-0843
13	Novartis Investigative Site	Chuo ku	Tokyo	Japan	103 0027
14	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0027
15	Novartis Investigative Site	Toshima-ku	Tokyo	Japan	171-0014

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 17, 2018
• Study Protocol - Mar 15, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03100500
• Other Study ID Numbers: CQVM149B1305
• First Posted: Apr 4, 2017
• Last Update Posted: Feb 7, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: QVM149,; Asthma,; Japanese,; Allergic asthma,; Allergy triggered asthma,; Reactive asthma,; Asthma attack,; Difficulty breathing
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Period Title: Overall Study
STARTED	51
COMPLETED	51
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Overall Participants	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (12.45)
Sex: Female, Male (Count of Participants)
Female	28 54.9%
Male	23 45.1%
Race/Ethnicity, Customized (Count of Participants)
Asian	51 100%
Race/Ethnicity, Customized (Count of Participants)
East Asian	51 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	A TEAE is any adverse event that started on or after the time of the first inhalation of study drug but not later than 7 days (30 days in the case of a SAE) after the last administration. A SAE is described as any adverse event that leads to death, is life-threatening, results in persistent or significant disability/incapacity, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event which is medically significant.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all participants who received at least one dose of study medication during this study.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
TEAEs	40 78.4%
SAEs	0 0%

2. Secondary Outcome

Title	Change From Baseline of Pre-Dose Forced Expiratory Volume in 1 Second (FEV1) Measured After 26 And 52 Weeks Treatment
Description	The pre-dose FEV1 was defined as the mean of the pre-dose 45 and 15 min FEV1 values prior to evening dose. 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. A positive change from baseline in FEV1 indicates improvement in lung function.
Time Frame	Baseline, Weeks 26 and 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective day are included.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
Baseline	2.1565 (0.58074)
Change at Week 26	0.2417 (0.26361)
Change at Week 52	0.1827 (0.26627)

3. Secondary Outcome

Title	Change From Baseline of Morning and Evening Peak Expiratory Flow (PEF) During 52 Weeks Treatment
Description	PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. PEF was analyzed separately in the morning and evening using an electronic Peak Flow Meter (ePEF). A positive change from baseline in PEF indicates improvement in lung function.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective post baseline month are included.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
Baseline, Morning PEF	342.88 (94.656)
Change through Weeks 1-52, Morning PEF	15.49 (49.089)
Baseline, Evening PEF	352.65 (92.624)
Change through Weeks 1-52, Evening PEF	9.34 (42.685)

4. Secondary Outcome

Title	Change From Baseline of Asthma Control Questionnaire (ACQ-7) After 26 And 52 Weeks Treatment
Description	The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question (question 7) was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.
Time Frame	Baseline, Weeks 26 and 52

Outcome Measure Data

Analysis Population Description

FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective day are included.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
Baseline	1.983 (0.5381)
Change at Week 26	-0.689 (0.6268)
Change at Week 52	-0.830 (0.6852)

5. Secondary Outcome

Title	Responder Rate of Participants Achieving the Minimal Important Difference (MID) of ACQ-7 ≥ 0.5 After 26 And 52 Weeks Treatment
Description	The ACQ-7 is a seven-item disease-specific instrument developed and validated to assess asthma control in participants. It consists of five items to assess symptoms and activity limitations, one question to assess rescue medication use, and one question to assess airway caliber (FEV1% predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question (question 7) was completed by the study investigator using data from the Master Scope spirometer. The proportion of participants who achieved an improvement of at least 0.5 in ACQ-7 (i.e. decrease of ACQ-7 score of at least 0.5 from baseline) at post-baseline visits were analyzed.
Time Frame	Weeks 26 and 52

Outcome Measure Data

Analysis Population Description

FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Number analyzed indicates the number of participants with data available for analysis at Weeks 26 and 52.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
Week 26	66.0 129.4%
Week 52	72.9 142.9%

6. Secondary Outcome

Title	Change From Baseline of Rescue Medication Use During 52 Weeks Treatment
Description	Based on the electronic-diary data, the total number of puffs of rescue medication per day over the 52 weeks were calculated and divided by the total number of days to derive the mean daily number of puffs of rescue medication taken for the participant.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

FAS consisted of all participants who entered the treatment epoch of this study and received at least one dose of study medication during this study. Participants with a value at both baseline and the respective post baseline month are included.

Arm/Group Title	QMF-149 150/320 μg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
Measure Participants	51
Baseline	0.56 (1.382)
Change through Weeks 1-52	-0.18 (0.499)

Adverse Events

Time Frame	Up to 52 weeks
Adverse Event Reporting Description	Safety Set consisted of all participants who received at least one dose of study medication during this study.
Arm/Group Title	QMF149 150/320 µg
Arm/Group Description	QMF-149 150/320 μg delivered as powder in hard capsules, once daily via Concept1 inhaler.
All Cause Mortality
	QMF149 150/320 µg
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Serious Adverse Events
	QMF149 150/320 µg
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Other (Not Including Serious) Adverse Events
	QMF149 150/320 µg
	Affected / at Risk (%)	# Events
Total	37/51 (72.5%)
Gastrointestinal disorders
Gastritis	2/51 (3.9%)
Infections and infestations
Bronchitis	6/51 (11.8%)
Nasopharyngitis	15/51 (29.4%)
Otitis media	2/51 (3.9%)
Pharyngitis	2/51 (3.9%)
Upper respiratory tract infection bacterial	3/51 (5.9%)
Investigations
Electrocardiogram QT prolonged	2/51 (3.9%)
Musculoskeletal and connective tissue disorders
Back pain	3/51 (5.9%)
Myalgia	3/51 (5.9%)
Respiratory, thoracic and mediastinal disorders
Asthma	28/51 (54.9%)
Oropharyngeal pain	2/51 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.