Clinical trial NCT00801853: A Study of the Treatment-Sparing Effects of AEROVANT™ AER 001 Inhalation Powder in Asthma Patients, AEROTRIAL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: asthma
allergy
atopy
atopic
wheeze
Lead sponsor: Aerovance, Inc.
Sponsor class: INDUSTRY
First posted: 2008-12-04
Enrollment: 424
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of exacerbation
timeFrame: 4 months
Secondary outcomes:
measure: In-clinic and daily pulmonary function
timeFrame: 4 months
measure: Time to exacerbation after randomization
timeFrame: 4 months
measure: Change from baseline in daily asthma symptom scores
timeFrame: 4 months
measure: Change from baseline in daily beta-agonist reliever use
timeFrame: 4 months
measure: Change from baseline in total IgE
timeFrame: 4 months
measure: Change from baseline in fractional concentration of expired nitric oxide (FENO)
timeFrame: 4 months
measure: Population pharmacokinetics
timeFrame: 4 months
measure: General safety evaluation including lung function, blood pressure, heart rate, respiratory rate, temperature, ECG parameters, safety laboratory tests.
timeFrame: 4 months
measure: SNP analysis for IL-4 and IL-13 relevant genes (Exploratory)
timeFrame: 4 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Pulmonary Associates of Mobile, P.C.
state: Alabama
city: Scottsdale
country: United States
facility: Allergy and Immunology Associates Ltd
state: Arizona
city: Huntington Beach
country: United States
facility: Allergy and Asthma Specialists Medical Group
state: California
city: San Diego
country: United States
facility: Allergy Associates Medical Group Inc.
state: California
city: San Diego
country: United States
facility: Institute of Healthcare Assessment Inc.
state: California
city: San Jose
country: United States
facility: Allergy and Asthma Associates of Santa Clara Valley Research Center
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research Inc.
state: California
city: Centenniel
country: United States
facility: Colorado Asthma and Allergy Research Centers, P.C.
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates P.C. and Research Center
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Miami
country: United States
facility: Florida Center for Asthma and Allergy Research
state: Florida
city: Tallahassee
country: United States
facility: Allergy and Asthma Diagnostic Treatment Center
state: Florida
city: Valrico
country: United States
facility: Partners in Asthma and Allergy Care, P.A.
state: Florida
city: Coeur d'Alene
country: United States
facility: Pulmonary Consultants of North Idaho
state: Idaho
city: Evansville
country: United States
facility: Deaconess Clinic Downtown
state: Indiana
city: Bangor
country: United States
facility: Allergy and Clinical Immunology
state: Maine
city: Boston
country: United States
facility: The Brigham and Womens Hospital Inc.
state: Massachusetts
city: North Dartmouth
country: United States
facility: North East Medical Research Associates, Inc
state: Massachusetts
city: Missoula
country: United States
facility: Cardiopulmonary Associates of Missoula
state: Montana
city: Summit
country: United States
facility: Pulmonary and Allergy Associates
state: New Jersey
city: Newburgh
country: United States
facility: ENT and Allergy Associates
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cincinatti
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research
state: Oklahoma
city: Eugene
country: United States
facility: Allergy and Asthma Associates/Oak Street Medical P.C.
state: Oregon
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Asthma and Allergy Research of New Jersey Inc.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Upland
country: United States
facility: Asthma and Allergy Research Associates, PA
state: Pennsylvania
city: Providence
country: United States
facility: Asthma, Nasal Disease and Allergy Research Center of New England
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Allergy and Asthma Research Center, P.A.
state: Texas
city: San Antonio
country: United States
facility: Discovery Clinical Trials, LLC
state: Texas
city: Abingdon
country: United States
facility: Johnston Memorial Hospital
state: Virginia
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Kórház - Rendelőintézet
city: Budapest
country: Hungary
facility: Gyógyír XI Kht ( XI Kerületi Tüdőgondozó)
city: Csorna
country: Hungary
facility: Margit Kórház
city: Deszk
country: Hungary
facility: Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórház
city: Siofok
country: Hungary
facility: Siofok Varos Korhaz-Rendelointezet
city: Szarvas
country: Hungary
facility: Szarvasi Tüdőgyógyász Kft.
city: Szazhalombatta
country: Hungary
facility: Men For Care Kft. Százhalom Egészségügyi Központ
city: Szombathely
country: Hungary
facility: Vas Megyei Markusovszky Lajos Általános, Rehabilitációs és Gyógyfürdő Kórház
city: Tatabánya
country: Hungary
facility: Komárom-Esztergom Megyei Önkormányzat Szent Borbála Kórháza
city: Érd
country: Hungary
facility: Érd Városi Önkormányzat Szakorvosi Rendelőintézet
city: Bialystok
country: Poland
facility: Prywatny Gabinet Internistyczno - Alergologiczny
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika Kliniczny Oddzial Pulmonologiczny
city: Bystra
country: Poland
facility: Specjalistyczny Zespol Chorob Pluc i Gruzlicy w Bystrej
city: Gdansk
country: Poland
facility: Medcare NZOZ
city: Krakow
country: Poland
facility: All-Med
city: Lodz
country: Poland
facility: NZOZ Centrum Alergologii prof. Krzysztof Buczylko
city: Lodz
country: Poland
facility: Poradnia Alergologii i Chorob Pluc SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlicki
city: Lublin
country: Poland
facility: AlergoTest SC
city: Strzelce Opolskie
country: Poland
facility: NZOZ Centrum Medyczne Lucyna Andrzej Dymek
city: Tarnów
country: Poland
facility: Alergomed Specjalistyczna Przychodnia Lekarska sp zoo
city: Barnsley
country: United Kingdom
facility: Barnsley District Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Burton on Trent
country: United Kingdom
facility: Queens Hospital
city: Bury St. Edmunds
country: United Kingdom
facility: Woolpit Health Centre
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Chesterfield
country: United Kingdom
facility: Avondale Surgery
city: Chesterfield
country: United Kingdom
facility: Chesterfield Royal Hospital
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
affiliation: University of Pittsburgh
name: Sally Wenzel, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.