Dose Finding Study for QAW039 in Asthma

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2011-001062-18-NL
• Date of registration: 29/05/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Dose Finding Study for QAW039 in Asthma
• Scientific title: A randomized, placebo-controlled, dose-ranging, multi-centre trial of QAW039 (1-450 mg p.o.), to investigate the effect on FEV1 and ACQ in patients with moderate-to-severe, persistent, allergic asthma, inadequately controlled with ICS therapy
• Date of first enrolment: 19/07/2012
• Target sample size: 950
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001062-18
• 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: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 15

Countries of recruitment

Argentina, Austria, Bulgaria, Canada, Colombia, Greece, Guatemala, Hungary, India, Japan, Mexico, Netherlands, Peru, Philippines, Poland, South Africa, United Kingdom, United States, Venezuela, Bolivarian Republic of

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed
2. Males and females of any race who are between 18 and 65 years old at the time informed
consent is obtained.
3. Physician diagnosis of asthma, as per GINA (2009) guidelines, and currently prescribed ICS therapy.
4. Patients with a pre-bronchodilator FEV1 value of 40% to 80% of individual predicted value at screening and at randomization, and the value at the randomization should be within 15% of the screening FEV1. The results of spirometry should meet the ATS/ERS criteria for acceptability and repeatability.
5. Patients must be allergic or atopic, as diagnosed historically or at screening visit by either a skin prick test (= 3mm diameter above background) or a positive specific IgE (e.g. RAST/CAP) test (=0.35 IU eq./ml).
6. Patients who are demonstrated to have reversible airway obstruction or airways hyperreactivity or have shown either of such responses in previous test(s) within 5 years.
• Reversible airway obstruction demonstrated at screening is defined as either: a. an increase of =12% and =200 ml in FEV1 over the patient’s pre-bronchodilator
value in litres or
b. an increase of =10% in % of predicted FEV1 over the patient’s prebronchodilator % of predicted FEV1
within 10-15 minutes after inhaling a total of 360 µg of albuterol or 400 µg salbutamol via MDI (reversibility test). The administration of albuterol or salbutamol for the reversibility test is to be within 30 minutes after pre-bronchodilator spirometry.
• A positive airways hyper-reactivity (AHR) test result is defined as a provoked fall in FEV1 of 20% (PC20) by methacholine at =8 mg/ml when not on ICS or =16 mg/ml on ICS therapy.
7. An ACQ score = 1.5 at randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 940
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives
of enrollment, whichever is longer.
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes (CRTh2 antagonists).
3. History of long QT syndrome or whose current QTc interval (Fridericia’s) is prolonged > 450 msec for males and females at screening as assessed by central ECG interpretation.
4. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
5. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use effective contraception during the study and for 4 days (5
half-lives) after treatment. Effective contraception methods are defined in the protocol.
7. Patients with serious co-morbidities including, but not limuted to, uncontrolled diabetes (HbA1c =8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune
diseases, other lung diseases including chronic bronchitis, chronic obstructive pulmonary disease or emphysema or other conditions characterised by eosinophilia and pulmonary symptoms (i.e. Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis,
eosinophilic pneumonia, etc.).
8. Acute illness other than asthma at the start of the study
9. History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma.
10. History of alcohol or other substance abuse.
11. Patients who have had a respiratory tract infection within 4 weeks of the screening visit.
Patients who develop a respiratory tract infection between screening and the randomization visit must be screen failed, and may be permitted to re-enroll at a later date.
12. Patients who have been hospitalized due to their asthma, or that have required treatment
with systemic steroids, within 6 weeks of the screening visit.
13. Patients with clinically significant laboratory abnormalities (not associated with the study
indication) at screening including (but not limited to):
• Total white blood cell count <2500 cells/µL at screening.
• AST or ALT>2.0 X ULN or total bilirubin >1.3 X ULN at screening.
• Estimated Glomerular Filtration Rate (eGFR) by the MDRD equation <55 mL/minute/1.73 m2 at screening.
14. Patients who have a clinically significant abnormality on a 12-lead ECG recorded within
one month prior to or at screening.
15. Current smokers or ex-smokers who stopped smoking within 6 months prior to screening or have a smoking history of = 10 pack years.
16. Patients with a body mass index (BMI) < 17 or > 40 kg/m2.


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

Health Condition(s) or Problem(s) studied

Moderate-to-severe, persistent, allergic asthma, inadequately controlled with ICS therapy
MedDRA version: 14.1 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

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

Intervention(s)

Product Code: QAW039
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 872365-14-5
Current Sponsor code: QAW039
Other descriptive name: QAW039-NXA.001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Code: QAW039
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 872365-14-5
Current Sponsor code: QAW039
Other descriptive name: QAW039-NXA.001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Code: QAW039
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 872365-14-5
Current Sponsor code: QAW039
Other descriptive name: QAW039-NXA.001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Code: QAW039
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 872365-14-5
Current Sponsor code: QAW039
Other descriptive name: QAW039-NXA.001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Morning FEV1

Timepoint(s) of evaluation of this end point: Visit 2 to 10 included

Main Objective: To demonstrate a clinically significant improvement in morning FEV1 in moderate to severe allergic asthmatics inadequately controlled by ICS therapy treated with QAW039 for 12 weeks compared to placebo.

Secondary Objective: - To demonstrate that QAW039 provides significantly superior control of asthmatic symptoms in these patients as measured by the ACQ, compared to placebo.
- To estimate the onset of efficacy as measured by spirometry assessments and the ACQ after 2, 4, 8 and 12 weeks of treatment.
- To characterize the dose response relationship among QAW039 doses with respect to trough FEV1 after 12 weeks of treatment.
- To assess safety and tolerability of QAW039 in a moderate to severe asthmatic population, particularly with regard to vital signs, ECG, heart rate, laboratory tests and adverse events, as compared to placebo.
- To compare the efficacy of QAW039 to that of montelukast as an add-on therapy to ICS in
inadequately controlled moderate-to-severe asthmatics.
- To assess the effect of QAW039 on asthma symptoms as measured by the Juniper asthma
diary.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - ACQ (visit 2 to 10 included)
- Trough FEV1 (visit 2 to 10 included)
- Jumper asthma diary (visit 3 to 10 included)
- Vital signs (visit 2 to 10 included)

Secondary end point(s): - ACQ
- Trough FEV1
- Jumper asthma diary
- Vital signs

Secondary ID(s)

CQAW039A2206

2011-001062-18-GR

Source(s) of Monetary Support

Novartis Pharma Services AG