Effect of Omalizumab in Patients With Severe Persistent Non-atopic Uncontrolled Asthma - Clinical Trial for Asthma | NCT01007149

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

omalizumab

Placebo

About this trial

This is an interventional basic science trial for Asthma focused on measuring Severe asthma,, non-atopic,, omalizumab

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Omalizumab

Placebo

Arm Description

Participants received subcutaneous injections of omalizumab every 2 weeks or every 4 weeks; dosage dependent on IgE level and body weight.

Participants received subcutaneous injections of placebo to omalizumab every 2 weeks or every 4 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline in the Expression of FcεRI Receptors of Blood Basophils

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

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)

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

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)

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

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

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

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

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.

Full Information

NCT ID

NCT01007149

First Posted

October 30, 2009

Last Updated

July 18, 2012

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01007149

Brief Title

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

Acronym

NATAIR

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

Severe asthma,, non-atopic,, omalizumab

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Omalizumab

Arm Type

Experimental

Arm Description

Participants received subcutaneous injections of omalizumab every 2 weeks or every 4 weeks; dosage dependent on IgE level and body weight.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants received subcutaneous injections of placebo to omalizumab every 2 weeks or every 4 weeks.

Intervention Type

Drug

Intervention Name(s)

omalizumab

Intervention Description

Omalizumab was supplied in 5mL vials with solution for subcutaneous injection.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo was supplied in vials with solution for subcutaneous injection.

Primary Outcome Measure Information:

Title

Change From Baseline in the Expression of FcεRI Receptors of Blood Basophils

Description

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.

Time Frame

Baseline and 16 weeks

Title

Change From Baseline in the Expression of FcεRI Receptors of Dendritic Cells

Description

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.

Time Frame

Baseline and 16 weeks

Secondary Outcome Measure Information:

Title

Change in Fractional Exhaled Nitric Oxide (FeNO)

Description

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.

Time Frame

Baseline and 4, 8, 12 and 16 weeks

Title

Change From Baseline in Induced Sputum Eosinophil Count

Description

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.

Time Frame

Baseline and 16 weeks

Title

Change From Baseline in Score of the Shortened Version of the Asthma Control Questionnaire (Symptoms Plus Short-acting β2-agonist)

Description

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.

Time Frame

Baseline and 16 weeks

Title

Change From Baseline in Nasal Symptom Global Score and Individual Components

Description

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.

Time Frame

Baseline and 16 weeks

Title

Physician and Patient Global Evaluation of Treatment Effectiveness

Description

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.

Time Frame

16 weeks

Title

Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to 16 Weeks

Description

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.

Time Frame

Baseline and 16 weeks

Title

Number of Patients With at Least One Asthma-related Event Over 16 Weeks

Description

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.

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Arnaud de Villeneuve

Country

France

Facility Name

Novartis Investigative Site

City

Bethune

Country

France

Facility Name

Novartis Investigative Site

City

Bordeaux

Country

France

Facility Name

Novartis Investigative Site

City

Clamart

Country

France

Facility Name

Novartis Investigative Site

City

Lyon

Country

France

Facility Name

Novartis Investigative Site

City

Nantes

Country

France

Facility Name

Novartis Investigative Site

City

Paris

Country

France

Facility Name

Novartis Investigative Site

City

Strasbourg

Country

France

Facility Name

Novartis Investigative Site

City

Suresnes

Country

France

Facility Name

Novartis Investigative Site

City

Toulouse

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

23579324

Citation

Garcia G, Magnan A, Chiron R, Contin-Bordes C, Berger P, Taille C, Devouassoux G, de Blay F, Couderc LJ, Didier A, O'Callaghan DS, Girodet PO, Bourdeix I, Le Gros V, Humbert M. A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma. Chest. 2013 Aug;144(2):411-419. doi: 10.1378/chest.12-1961.

Results Reference

derived

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

Asthma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial