Evaluation of the efficacy and safety of QMF149 vs Mometasone in patients with asthma

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-002529-21-DE
• Date of registration: 23/10/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Evaluation of the efficacy and safety of QMF149 vs Mometasone in patients with asthma
• Scientific title: AA multicenter randomized 52 week treatment double-blind, triple dummy parallel group study to assess the efficacy and safety of QMF149 compared to mometasone furoate in patients with asthma
• Date of first enrolment: 06/01/2016
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002529-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: triple-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, China, Colombia, Croatia, Czech Republic, Egypt, Estonia, Germany, Guatemala, Hungary, India, Ireland, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, United Kingdom

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with a diagnosis of asthma, for a period of at least 1 year prior to Visit 1 (Screening)
2. Patients who have used medium or high dose ICS or low dose of LABA/ICS combinations for asthma for at least 3 months and at stable doses for at least 1 month prior to Visit 1
3. Patients must have ACQ-7 score = 1.5 at Visit 101 and at Visit 102 (prior to double-blind treatment) and qualify for treatment with medium or high dose LABA/ICS
4. Pre-bronchodilator = 50% FEV1 of < 85% of the predicted normal value for the patient after withholding bronchodilators at both Visit 101 and 102,according to ATS/ERS criteria.
• Withholding period of bronchodilators prior to spirometry: SABA for = 6 hours and FDC or free combinations of ICS/LABA for = 48 hours, SAMA for = 8 hours, ,xanthines >=07days.
• A one-time repeat/ re-testing of percent predicted FEV1 (prebronchodilator FEV1) is allowed at visit 101 and at visit 102. Spacer devices are permitted for reversibility testing only.
5. 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:
- 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
- Reversibility should be repeated once
- 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
• Patients who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years. This includes or use of nicotine inhalers such as e-cigarettes at the time of Visit 1
• Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening)
• 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 the investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Patients may be rescreened 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.
• Patients who have a clinically significant ECG abnormality at Visit 101 (Start of Run- In epoch) and at any time between Visit 101 and Visit 102 (including unscheduled ECG). ECG evidence of myocardial infarction at Visit 101 (via central reader) should be clinically assessed by the investigator with supportive documentation.
• Patients with a history of hypersensitivity tolactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof
• Patients who have not achieved an acceptable spirometry results at Visit 101 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability (rescreening allowed only once).
Repeat spirometry may be allowed once in an adhoc visit if the spirometry did not qualify due to ATS/ERS criteria. If the patient fails the repeat assessment, the patient may be rescreened once
• Patients on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout
the course of the study.
•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 for 30 days after stopping of study treatment.
•LAMA within 3 months prior to visit 101


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Asthma
MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Indacaterol acetate / mometasone furoate
Product Code: QMF149, 150/160 µg
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL ACETATE
Other descriptive name: INDACATEROL ACETATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: MOMETASONE FUROATE
Current Sponsor code: MF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 160-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Name: Indacaterol acetate/Mometasone furoate
Product Code: QMF149, 150/320 µg
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL ACETATE
Other descriptive name: INDACATEROL ACETATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: MOMETASONE FUROATE
Current Sponsor code: MF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 320-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Asmanex Twisthaler
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: MOMETASONE FUROATE
Current Sponsor code: MF
Other descriptive name: MOMETASONE FUROATE
Concentration unit: µg microgram(s)
Concentra

Primary Outcome(s)

Main Objective: To demonstrate the superiority of either QMF149 150/160 µg delivered via Concept1 o.d. (in the evening) to MF 400 µg o.d. (in the evening) delivered via Twisthaler® or QMF149 150/320 µg delivered via Concept1 o.d. (in the evening) to MF 800 µg delivered via Twisthaler® (delivered as 400 µg b.i.d.) in terms of FEV1 at 26 weeks.

Secondary Objective: To compare QMF149 150/160 µg o.d. to MF 400 µg o.d. or QMF149 150/320 µg to MF 800 µg (delivered as 400 µg b.i.d.) in terms of:
- through FEV1 at week 52
- pre-dose FEV1 at week 4 and 12
- FEV1, FVC and FEF over 52 weeks of treatment.
- PEF over 26 and 52 weeks
- ACQ-7 at week 4, 12, 26 and 52 weeks
- Percentage patients with MID of ACQ>=0,5 at week 26 and 52
- daily e-diary over 52 weeks
- rescue medication use over 26 and 52 weeks
- asthma exacerbation over 52 weeks
- % rescue medication free days over 26 and 52 weeks
- quality of life assessed by AQLQ-S 12 at 52 weeks
- incidence of composite endpoint of serious asthma outcomes
- Adverse event, vital signs, ECG and laboratory analysis

To compare QMF149 150/320 µg with salmeterol xinafoate/fluticasone propionate 50/500 µg via Accuhaler® for all the listed secondary endpoints above as well as through FEV1 at week 26.

Timepoint(s) of evaluation of this end point: 26 weeks

Primary end point(s): Comparison between QMF149 and Mometasone furoate in terms of FEV1.

Secondary Outcome(s)

Secondary end point(s): Comparison between QMF149 and Mometasone furoate in terms of ACQ-7

Timepoint(s) of evaluation of this end point: 26 weeks

Secondary ID(s)

CQVM149B2301

2015-002529-21-GB

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact: