A Study of the Treatment-Sparing Effects of AEROVANT™ AER 001 Inhalation Powder in Asthma Patients, AEROTRIAL

Study Overview
=================
Brief Summary
-----------------
A multi-center, Phase IIb, double-blind, randomized, placebo controlled, parallel-group, repeated-dose study in male and female patients with moderate to severe asthma in which patients will be stabilized on AEROVANT then doses of inhaled corticosteroids and LABA will be tapered. The hypothesis is that AEROVANT will improve asthma symptom control and decrease the need for inhaled corticosteroids and LABA, thus improving exacerbation incidence compared to placebo. Incidence of asthma exacerbation is the primary endpoint.

Official Title
-----------------
A Phase IIb Study to Investigate the Treatment-Sparing Effects of AEROVANT™ AER 001 Inhalation Powder in Asthma Patients Not Fully Controlled on Current Therapy

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Aerovant
* Drug: Aerovant
* Drug: Aerovant
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patient, ≥ 18 years of age with a documented clinical history of asthma, has been treated for asthma and, in the opinion of the Investigator, is not fully controlled on current asthma therapy. Patient satisfies, or has satisfied in the past, the GINA definition of moderate persistent to severe persistent asthma. Patient has been maintained on moderate-to-high doses of ICS and LABA in the form of combination therapy or as individual agents (equivalent to fluticasone ≥ 250 mcg bid and salmeterol ≥ 50 mcg bid for ≥ 4 weeks before Screening [Visit 1]). Patient has experienced an asthma exacerbation at least once in the past 2 years (defined here as use of physician prescribed oral corticosteroids or asthma requiring treatment increase approximately 4 times the baseline dose of inhaled corticosteroids or hospitalization due to asthma). Patient has a pre-bronchodilator FEV1 ≥ 50% but ≤ 95% of the predicted value at both Screening (Visit 1) and Visit 2. Patient demonstrates ≥ 12% reversibility (and a ≥ 200 mL difference) from prebronchodilator FEV1 within 15 to 30 minutes of receiving up to 4 puffs of a short-acting beta-agonist at Screening (Visit 1) or has ≥ 10% reversibility from pre-bronchodilator FEV1 plus a documented reversibility of ≥ 12% within the previous 12 months (documented methacholine or histamine sensitivity (PC20) <8mg/mL is also acceptable evidence or reversible airways disease). Patient scores ≤ 20 on The Asthma Control Test™ at Screening (Visit 1) and Visit 2. Female patient of childbearing potential or male patient and his female partner are practicing adequate and effective forms of contraception and agree to continue for the duration of the study. If female, must have a negative urine pregnancy test. Patient has a pre-study medical history, physical examination, 12-Lead ECG, and safety laboratory test results within normal reference ranges or clinically acceptable to the Investigator. Patient is a non-smoker for at least 6 months before Screening (Visit 1) and has a < 10 pack/year history of smoking. Patient is medically stable for at least 8 weeks before Randomization (Visit 2), and the Investigator does not consider study participation to place the patient at increased risk of AEs (with the exception of possible asthma exacerbations). Patient is able and willing to give written informed consent. Exclusion Criteria: Patient has a current diagnosis of respiratory disorder other than asthma (e.g., chronic bronchitis, bronchiectasis, emphysema, chronic obstructive pulmonary disease [COPD], etc). Patient has received oral corticosteroid treatment within 8 weeks of Randomization (Visit 2)or patient has been intubated for ventilation in the past 5 years. Patient has used any leukotriene antagonist within 1 week before Screening (Visit 1) or anti-IgE medications within 4 weeks of Screening (Visit 1). Female patient is pregnant, breastfeeding, or not using an adequate method of contraception. Patient has a clinically relevant medical history of very severs asthma that would preclude steroid reduction or sufficient compliance with the protocol. Patient uses concomitant medications, including herbal, over-the-counter, or prescription medicines that, in the opinion of the Investigator, may affect the outcome of study endpoints and/or well-being of the patient. Patient has a history of alcohol or substance abuse within 2 years of Screening (Visit 1). Patient consumes more than 28 units (male) or 21 units (female) of alcohol a week (unit = 1 glass of wine = 1measure of spirits = ½ pint or 8 fluid ounces of beer). Patient cannot communicate reliably with the Investigator or is unlikely to cooperate with the requirements of the study. Patient has previously taken AEROVANT™ or another formulation of AER 001 (e.g., BAY 16-9996, pitrakinra). Patient has participated in any clinical trial involving use of an investigational drug within 12 weeks of first dose of study drug.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerovant 1<br>Aerovant 1mg bid | Drug: Aerovant<br>* Aerovant 1mg bid (dry powder)<br>* Other names: AER 001 DPI, BAY 16-9996, pitrakinra;|
| Experimental: Aerovant 2<br>Aerovant 3mg bid | Drug: Aerovant<br>* Aerovant 3mg bid (dry powder)<br>* Other names: AER 001 DPI, BAY 16-9996, pitrakinra;|
| Experimental: Aerovant 3<br>Aerovant 10mg bid | Drug: Aerovant<br>* Aerovant 10mg bid (dry powder)<br>* Other names: AER 001 DPI, BAY 16-9996, pitrakinra;|
| Placebo Comparator: Placebo Control<br>Placebo Control | Other: placebo<br>* placebo control (dry powder)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of exacerbation |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-clinic and daily pulmonary function |  | 4 months | 
| Time to exacerbation after randomization |  | 4 months | 
| Change from baseline in daily asthma symptom scores |  | 4 months | 
| Change from baseline in daily beta-agonist reliever use |  | 4 months | 
| Change from baseline in total IgE |  | 4 months | 
| Change from baseline in fractional concentration of expired nitric oxide (FENO) |  | 4 months | 
| Population pharmacokinetics |  | 4 months | 
| General safety evaluation including lung function, blood pressure, heart rate, respiratory rate, temperature, ECG parameters, safety laboratory tests. |  | 4 months | 
| SNP analysis for IL-4 and IL-13 relevant genes (Exploratory) |  | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma, allergy, atopy, atopic, wheeze