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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Aerovant; Drug: Aerovant; Drug: Aerovant; Other: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 424
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Balassagyarmat, Hungary
    • Dr. Kenessey Albert Kórház - Rendelőintézet
  • Budapest, Hungary
    • Gyógyír XI Kht ( XI Kerületi Tüdőgondozó)
  • Csorna, Hungary
    • Margit Kórház
  • Deszk, Hungary
    • Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza
  • Nyiregyhaza, Hungary
    • Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórház
  • Siofok, Hungary
    • Siofok Varos Korhaz-Rendelointezet
  • Szarvas, Hungary
    • Szarvasi Tüdőgyógyász Kft.
  • Szazhalombatta, Hungary
    • Men For Care Kft. Százhalom Egészségügyi Központ
  • Szombathely, Hungary
    • Vas Megyei Markusovszky Lajos Általános, Rehabilitációs és Gyógyfürdő Kórház
  • Tatabánya, Hungary
    • Komárom-Esztergom Megyei Önkormányzat Szent Borbála Kórháza
  • Érd, Hungary
    • Érd Városi Önkormányzat Szakorvosi Rendelőintézet
• Poland
  • Bialystok, Poland
    • Prywatny Gabinet Internistyczno - Alergologiczny
  • Bydgoszcz, Poland
    • 10 Wojskowy Szpital Kliniczny z Poliklinika Kliniczny Oddzial Pulmonologiczny
  • Bystra, Poland
    • Specjalistyczny Zespol Chorob Pluc i Gruzlicy w Bystrej
  • Gdansk, Poland
    • Medcare NZOZ
  • Krakow, Poland
    • All-Med
  • Lodz, Poland
    • NZOZ Centrum Alergologii prof. Krzysztof Buczylko
  • Lodz, Poland
    • Poradnia Alergologii i Chorob Pluc SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlicki
  • Lublin, Poland
    • AlergoTest SC
  • Strzelce Opolskie, Poland
    • NZOZ Centrum Medyczne Lucyna Andrzej Dymek
  • Tarnów, Poland
    • Alergomed Specjalistyczna Przychodnia Lekarska sp zoo
• United Kingdom
  • Barnsley, United Kingdom
    • Barnsley District Hospital
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital
  • Burton on Trent, United Kingdom
    • Queens Hospital
  • Bury St. Edmunds, United Kingdom
    • Woolpit Health Centre
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Chesterfield, United Kingdom
    • Avondale Surgery
  • Chesterfield, United Kingdom
    • Chesterfield Royal Hospital
  • Colchester, United Kingdom
    • Colchester General Hospital
  • Glasgow, United Kingdom
    • Gartnavel General Hospital
  • Leicester, United Kingdom
    • Glenfield Hospital
  • London, United Kingdom
    • Hammersmith Hospital
  • Swansea, United Kingdom
    • Morriston Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States
      • Pulmonary Associates of Mobile, P.C.
  • Arizona
    • Scottsdale, Arizona, United States
      • Allergy and Immunology Associates Ltd
  • California
    • Huntington Beach, California, United States
      • Allergy and Asthma Specialists Medical Group
    • San Diego, California, United States
      • Allergy Associates Medical Group Inc.
    • San Diego, California, United States
      • Institute of Healthcare Assessment Inc.
    • San Jose, California, United States
      • Allergy and Asthma Associates of Santa Clara Valley Research Center
    • Walnut Creek, California, United States
      • Allergy and Asthma Clinical Research Inc.
  • Colorado
    • Centenniel, Colorado, United States
      • Colorado Asthma and Allergy Research Centers, P.C.
    • Colorado Springs, Colorado, United States
      • Asthma and Allergy Associates P.C. and Research Center
    • Denver, Colorado, United States
      • National Jewish Health
  • Florida
    • Miami, Florida, United States
      • Florida Center for Asthma and Allergy Research
    • Tallahassee, Florida, United States
      • Allergy and Asthma Diagnostic Treatment Center
    • Valrico, Florida, United States
      • Partners in Asthma and Allergy Care, P.A.
  • Idaho
    • Coeur d'Alene, Idaho, United States
      • Pulmonary Consultants of North Idaho
  • Indiana
    • Evansville, Indiana, United States
      • Deaconess Clinic Downtown
  • Maine
    • Bangor, Maine, United States
      • Allergy and Clinical Immunology
  • Massachusetts
    • Boston, Massachusetts, United States
      • The Brigham and Womens Hospital Inc.
    • North Dartmouth, Massachusetts, United States
      • North East Medical Research Associates, Inc
  • Montana
    • Missoula, Montana, United States
      • Cardiopulmonary Associates of Missoula
  • New Jersey
    • Summit, New Jersey, United States
      • Pulmonary and Allergy Associates
  • New York
    • Newburgh, New York, United States
      • ENT and Allergy Associates
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Wake Forest University
  • Ohio
    • Cincinatti, Ohio, United States
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States
      • Bernstein Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Allergy, Asthma and Clinical Research Center
    • Oklahoma City, Oklahoma, United States
      • IPS Research
  • Oregon
    • Eugene, Oregon, United States
      • Allergy and Asthma Associates/Oak Street Medical P.C.
    • Portland, Oregon, United States
      • Allergy Associates Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Asthma and Allergy Research of New Jersey Inc.
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Upland, Pennsylvania, United States
      • Asthma and Allergy Research Associates, PA
  • Rhode Island
    • Providence, Rhode Island, United States
      • Asthma, Nasal Disease and Allergy Research Center of New England
  • South Carolina
    • Greenville, South Carolina, United States
      • Greenville Pharmaceutical Research
    • Spartanburg, South Carolina, United States
      • Spartanburg Medical Research
  • Texas
    • Houston, Texas, United States
      • Baylor College of Medicine
    • San Antonio, Texas, United States
      • Allergy and Asthma Research Center, P.A.
    • San Antonio, Texas, United States
      • Discovery Clinical Trials, LLC
  • Virginia
    • Abingdon, Virginia, United States
      • Johnston Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Patient satisfies, or has satisfied in the past, the GINA definition of moderate persistent to severe persistent asthma.
3. 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]).
4. 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).
5. Patient has a pre-bronchodilator FEV1 ≥ 50% but ≤ 95% of the predicted value at both Screening (Visit 1) and Visit 2.
6. 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).
7. Patient scores ≤ 20 on The Asthma Control Test™ at Screening (Visit 1) and Visit 2.
8. 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.
9. 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.
10. Patient is a non-smoker for at least 6 months before Screening (Visit 1) and has a < 10 pack/year history of smoking.
11. 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).
12. Patient is able and willing to give written informed consent.

Exclusion Criteria:

1. Patient has a current diagnosis of respiratory disorder other than asthma (e.g., chronic bronchitis, bronchiectasis, emphysema, chronic obstructive pulmonary disease [COPD], etc).
2. 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.
3. Patient has used any leukotriene antagonist within 1 week before Screening (Visit 1) or anti-IgE medications within 4 weeks of Screening (Visit 1).
4. Female patient is pregnant, breastfeeding, or not using an adequate method of contraception.
5. Patient has a clinically relevant medical history of very severs asthma that would preclude steroid reduction or sufficient compliance with the protocol.
6. 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.
7. Patient has a history of alcohol or substance abuse within 2 years of Screening (Visit 1).
8. 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).
9. Patient cannot communicate reliably with the Investigator or is unlikely to cooperate with the requirements of the study.
10. Patient has previously taken AEROVANT™ or another formulation of AER 001 (e.g., BAY 16-9996, pitrakinra).
11. Patient has participated in any clinical trial involving use of an investigational drug within 12 weeks of first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aerovant 1; Aerovant 1mg bid	Drug: Aerovant; Aerovant 1mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 3mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 10mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra
EXPERIMENTAL: Aerovant 2; Aerovant 3mg bid	Drug: Aerovant; Aerovant 1mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 3mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 10mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra
EXPERIMENTAL: Aerovant 3; Aerovant 10mg bid	Drug: Aerovant; Aerovant 1mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 3mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra; Drug: Aerovant; Aerovant 10mg bid (dry powder); Other Names: AER 001 DPI, BAY 16-9996, pitrakinra
PLACEBO_COMPARATOR: Placebo Control	Other: placebo; placebo control (dry powder)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of exacerbation	4 months

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Aerovance, Inc.
• Investigators: Principal Investigator: Sally Wenzel, M.D., University of Pittsburgh

Publications and helpful links

General Publications

• Slager RE, Otulana BA, Hawkins GA, Yen YP, Peters SP, Wenzel SE, Meyers DA, Bleecker ER. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor alpha antagonist. J Allergy Clin Immunol. 2012 Aug;130(2):516-22.e4. doi: 10.1016/j.jaci.2012.03.030. Epub 2012 Apr 26.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): February 1, 2010
• Study Completion (ACTUAL): February 1, 2010

Study Registration Dates

• First Submitted: December 1, 2008
• First Submitted That Met QC Criteria: December 3, 2008
• First Posted (ESTIMATE): December 4, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 27, 2011
• Last Update Submitted That Met QC Criteria: January 25, 2011
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: asthma; allergy; atopy; wheeze; atopic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interleukin-4
• Other Study ID Numbers: PPD/2007/AER 001 DPI/2b