Effect of Omalizumab in Patients With Severe Persistent Non-atopic Uncontrolled Asthma (NATAIR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01007149
First received: October 30, 2009
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

This study will assess the change in the expression of FcεRI receptors of blood basophils and dendritic cells after 16 weeks of treatment with omalizumab as compared with placebo, in adult patients with non-atopic severe persistent asthma, uncontrolled despite optimal therapy.


Condition Intervention Phase
Asthma
Drug: omalizumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A 16-week Treatment, Multicenter, Randomized, Double Blind, Placebo-controlled, Parallel-group Study to Assess the Effect of Omalizumab on the Expression of FcεRI Receptors of Blood Basophils and Dendritic Cells in Patients With Severe Persistent Non-atopic Asthma, Uncontrolled Despite Optimal Therapy

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in the Expression of FcεRI Receptors of Blood Basophils [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of blood basophils (mean fluorescence intensity(MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value.

  • Change From Baseline in the Expression of FcεRI Receptors of Dendritic Cells [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of dendritic cells (mean fluorescence intensity (MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value.


Secondary Outcome Measures:
  • Change in Fractional Exhaled Nitric Oxide (FeNO) [ Time Frame: Baseline and 4, 8, 12 and 16 weeks ] [ Designated as safety issue: No ]
    FeNO was measured at baseline, and after 4, 8, 12 and 16 weeks of treatment. Absolute change in FeNO was expressed at each time point versus baseline value.

  • Change From Baseline in Induced Sputum Eosinophil Count [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    The induced sputum eosinophil count was measured in a subset of patients in selected centers. Sputum samples were collected at screening and Week 16. Sputum eosinophil count was expressed as a percentage of total nonsquamous cells. Absolute change in sputum eosinophil count was expressed versus baseline value.

  • Change From Baseline in Score of the Shortened Version of the Asthma Control Questionnaire (Symptoms Plus Short-acting β2-agonist) [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    The shortened version of the asthma control questionnaire (symptoms plus β2-agonist) consists of 6 subscores (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze and rescue short-acting β2-agonist use) between 0 and 6 (0 = no impairment; 6 = maximum impairment) and a total score between 0 and 6 (subscores mean value). Absolute change in total score and subscores count was expressed versus baseline value. A decrease in score indicates improvement.

  • Change From Baseline in Nasal Symptom Global Score and Individual Components [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Nasal symptom score calculated from six scales assessing the nasal symptom severity (sneezing, runny nose, congestion, itchy nose, postnasal drip and nasal symptoms overall). These six scores were rated on a scale from 1 to 7, with 7 being the worst rating. Absolute changes in these six scores were expressed versus baseline values. A negative change indicates improvement. The range of the global score was from 1 to 7, since this is the mean value of all the subscores.

  • Physician and Patient Global Evaluation of Treatment Effectiveness [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    The GETE is an assessment of asthma symptoms controlled in response to asthma treatment. The evaluation was performed independently by both investigator and patient using the same 5 point scale. The scale points are: excellent, good, moderate, poor and worsening. A good or excellent response is suggested as a means of defining a patient who has responded to treatment.

  • Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to 16 Weeks [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards. At least three maneuvers were performed at each sampling timepoint. The FEV1 recorded was taken from the maneuver obtained from the single best test curve. The best test curve was defined as the spirogram that gave the largest FEV1.

  • Number of Patients With at Least One Asthma-related Event Over 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Asthma-related events were: unscheduled medical visits, emergency room visits and hospitalizations. Details of exacerbations requiring oral or IV corticosteroids were recorded at each visit.


Enrollment: 79
Study Start Date: September 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omalizumab
Participants received subcutaneous injections of omalizumab every 2 weeks or every 4 weeks; dosage dependent on IgE level and body weight.
Drug: omalizumab
Omalizumab was supplied in 5mL vials with solution for subcutaneous injection.
Placebo Comparator: Placebo
Participants received subcutaneous injections of placebo to omalizumab every 2 weeks or every 4 weeks.
Drug: Placebo
Placebo was supplied in vials with solution for subcutaneous injection.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Severe persistent asthma with the following characteristics:

  • Uncontrolled according to Global Initiative for Asthma (GINA) 2007 guidelines and at least 2 exacerbations having required systemic corticosteroid and/or at least 1 hospitalization or emergency room visit in the past year.
  • Treated with high-dose inhaled corticosteroid (i.e. > 1,000 µg beclometasone dipropionate equivalent per day) plus inhaled long-acting β2 agonist (with or without maintenance oral corticosteroid).
  • Non-atopic, i.e. negative blood multiallergic testing and negative Aspergillus-specific IgE-radio allergosorbent blood test and negative skin prick tests to a battery of common aeroallergens

Exclusion Criteria:

  • Current smokers or smoking history stopped for less than 3 years or > 10 pack years.
  • Asthma exacerbation during the 4 weeks prior to randomization.
  • Active lung disease other than non-atopic asthma.
  • Patients with an active cancer, a suspicion of cancer or any history of cancer with less than 5 disease free years.
  • Pregnant or nursing (lactating) women.
  • Treatment with omalizumab.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01007149

Locations
France
Novartis Investigative Site
Arnaud de Villeneuve, France
Novartis Investigative Site
Bethune, France
Novartis Investigative Site
Bordeaux, France
Novartis Investigative Site
Clamart, France
Novartis Investigative Site
Lyon, France
Novartis Investigative Site
Nantes, France
Novartis Investigative Site
Paris, France
Novartis Investigative Site
Strasbourg, France
Novartis Investigative Site
Suresnes, France
Novartis Investigative Site
Toulouse, France
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01007149     History of Changes
Other Study ID Numbers: CIGE025AFR05, 2009-010937-38
Study First Received: October 30, 2009
Results First Received: February 20, 2012
Last Updated: July 18, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:
Severe asthma,
non-atopic,
omalizumab

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Omalizumab
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 16, 2014