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A 52-week, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of QAW039 when added to existing asthma therapy in patients with uncontrolled severe asthma

PHRR160620-001285

CQAW039A2307

2016-CT0338

A 52-week, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of QAW039 when added to existing asthma therapy in patients with uncontrolled severe asthma

Study of efficacy and safety of QAW039 in male and female patients (≥12 years) with severe asthma inadequately controlled with standard of care asthma treatment.

Regime Classification Priority
2010 - 2016 Health Technology Development Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2016-10-03 13 2017-11-03 2019-10-12

Completed

Institution Classification Region LTO #
Novartis Healthcare Philippines, Inc. Private Business NCR CDRR-NCR-S-1
Institution Classification Region LTO #
PAREXEL Clinical Research (Philippines) Ltd. Corp. Private Business NCR CDRR-NCR-CRO-4
Name E-Mail Institution and Institution Address
Anna Liza Calingasin anna_liza.calingasin@novartis.com Novartis Healthcare Philippines, Inc. 5F Ayala North Exchange Tower 1 Amorsolo corner Salcedo Streets Legaspi Village, Makati City 1229
Name E-Mail Institution and Institution Address
Ivy Emily Peneyro-Vergara ivy_emily.peneyro-vergara@novartis.com Novartis Healthcare Philippines, Inc. 5F Ayala North Exchange Tower 1 Amorsolo corner Salcedo Streets Legaspi Village, Makati City 1229
Name Expertise Affiliation
Aileen D. Wang, MD Pulmonologist Manila Doctors Hospital
Araceli Maliwat-Galapon, MD Pulmonologist St. Michael Family Hospital
Joven Roque V. Gonong, MD Pulmonologist Lung Center of the Philippines
Maria Janeth Samson, MD Pulmonologist St. Luke's Medical Center - Quezon City
Tito C. Atienza, MD Pulmonologist Veterans Memorial Medical Center
Project Location Institutional Ethics Review Board
Manila Doctors Hospital Manila Doctors Hospital Institutional Review Board
St. Michael Family Hospital N/A
Lung Center of the Philippines Lung Center of the Philippines Ethics Review Committee
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board
Veterans Memorial Medical Center Veterans Memorial Medical Center Ethics Review Committee

uncontrolled severe asthma

In patients with severe asthma and high eosinophil counts (≥250 cells/μl) receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch.

In patients with severe asthma receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch.

In patients with severe asthma and high eosinophil counts (≥250 cells/μl) receiving SoC asthma therapy:

  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in Asthma Quality of Life Questionnaire (AQLQ+12) scores at the end of the 52-week active-treatment epoch.
  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score at the end of the 52-week active-treatment epoch.
  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in pre-dose FEV1 at the end of the 52-week active-treatment epoch.
  • To assess the safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, with respect to adverse events, electrocardiograms (ECGs), vitals sign, laboratory tests and hypersensitivity reactions.


In all patients with severe asthma receiving SoC asthma therapy:

  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in Asthma Quality of Life Questionnaire (AQLQ+12) scores at the end of the 52-week active-treatment epoch.
  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score at the end of the 52-week active-treatment epoch.
  • To demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline in pre-dose FEV1 at the end of the 52-week active-treatment epoch.
  • To assess the safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, with respect to adverse events, electrocardiograms (ECGs), vitals sign, laboratory tests and hypersensitivity reactions.

Completed

  • Argentina
  • Australia
  • Austria
  • Belgium
  • Brazil
  • China
  • Denmark
  • Estonia
  • Finland
  • France
  • Germany
  • Greece
  • Guatemala
  • Hungary
  • Ireland
  • Latvia
  • Lithuania
  • Philippines
  • Poland
  • Romania
  • Singapore
  • Spain
  • Switzerland
  • United Kingdom
  • United States
  • Vietnam

Clinical Trial

CQAW039A2307

2016115102935

2016-06-09

0000-00-00

25

34

The sites were able to randomize 34 patients in the study and over recruit.

2016-10-03

Inclusion Criteria

  • Written informed consent must be obtained within 14 days prior to or at Visit 1 before any assessment is performed including any adjustment to asthma medication.
  • Male and female patients aged ≥12 years.
  • Patients must have a diagnosis of asthma (according to GINA 2015) for a period of at least 24 months prior to Visit 1.
  • Patients have been treated with high-dose inhaled corticosteroids plus a LABA (or alternate therapy: montelukast or theophylline or tiotropium) with or without maintenance oral corticosteroids for at least 3 months prior to Visit 1(See GINA 2015 for the definition of high dose ICS). The doses must have been stable for at least 4
    weeks prior to Visit 1.
  • FEV1 of ≥40% and ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Visit 1 and Visit 101.
  • Demonstration of inadequate control of asthma based on an ACQ score ≥1.5 at Visit 1.
  • A history of 2 or more asthma exacerbations within the 12 months prior to Visit 1 that required either:
    • Treatment with systemic corticosteroids (tablets, suspension or injection)               
    • OR
    • Hospitalization (defined as an inpatient stay or >24-hour stay in an observation area in the emergency room of other equivalent facility.
  • A clinical diagnosis of asthma supported by at least one of the following:

- An increase of ≥12% and ≥200 ml in FEV1 within 30 minutes after administration of 400 mcg of salbutamol/albuterol (or equivalent dose) prior to randomization. Spacer devices are not permitted during reversibility testing. All patients must perform a reversibility test at Visit 1. If reversibility is not demonstrated at Visit 1*, the following historical information may be used:                                                                   
- Documented evidence of reversibility that was performed according to ATS/ERS guidelines (ATS/ERS 2005) with the 2 years prior to Visit 1. Where a patient is assessed as eligible based on historical evidence of reversibility, a copy of the original printed spirometry report with relevant spirometry tracings must be available as source documentation.                                    
- Documented evidence of a positive airways hyper-reactivity (AHR) test result within the 2 years prior to or at Visit 101, defined as a provoked fall in FEV1 of 20% by methacholine at ≤8 mg/ml (or histamine ≤10 mg/ml or acetylcholine when not on ICS or ≤16 mg/ml or histamine ≤20 mg/ml or acetylcholine

Exclusion Criteria

  • Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
  • Subjects who have participated in another trial of QAW039 (i.e. subject received study medication [active (QAW039), placebo or other].
  • Patients with a resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) at Visit 1 or at Visit 101.
  • Patients with a history of malignancy of any organ, treated or untreated, whether or not there is evidence of local recurrence ofmetastases, with the exception of local basal cell carcinoma of the skin.
  • 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.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
  • Patients who have a clinically significant laboratory abnormality at Visit 1 or Visit 101
  • Patients with serious co-morbidities including, but not limited to, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases.
  • Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, or >2 mg of pitavastatin. Statin doses less than or equal to these doses as well as other statins will be permitted during the study.
  • Patients on any statin therapy with a CK level >2 X ULN at Visit 1.

Interventional

QAW039A/Fevipiprant

The following investigational treatment will be supplied by Novartis to the study sites:
-Name: QAW039
- Formulation: tablet
- Unit dose: 2 strengths: 150 mg and 450 mg
- Name: QAW039 placebo
- Formulation: tablet
 Unit dose: matching placebo to QAW039 150 mg, matching placebo to QAW039 450 mg
The investigational treatment (tablets) will be supplied in bottles. The matching placebos for
QAW039 will be identical in appearance to their active counterparts and will be identically
packaged.

Date Amendment Classification Reason
2016-09-26 Amendments related to the protocol Informed consent
2017-07-17 Amendments related to the protocol Informed consent

Randomized

Double Blind

This study uses a randomized, multicenter, double-blind, placebo-controlled parallel-group study design in which QAW039 or placebo is added to GINA steps 4 and 5 asthma therapy

Parallel

The overall purpose of this study is to determine the efficacy and safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, when added to GINA steps 4 and 5 standard-of- care (SoC) asthma therapy (GINA 2015)†, in patients with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ μl). Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2015).
The study will also determine the efficacy and safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, in the overall study population.

This approach will permit the determination of the effect of QAW039 in reducing asthma exacerbations in the subset of patients with severe asthma and high eosinophil counts as well as in the overall study population regardless of eosinophil counts.
†High dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids.

Phase II/III

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