A Prospective, Randomized, Double-Blind Study of the Efficacy of Omalizumab (Xolair) in Atopic Asthmatics With Good Lung Capacity Who Remain Difficult to Treat (EXACT) (EXACT)

This was a multicenter, parallel-group, double-blind, randomized, placebo-controlled study that enrolled 333 subjects. These subjects were 12-75 years old with atopic asthma, had elevated serum total Immunoglobulin E (IgE), had a baseline forced expiratory volume in 1 second (FEV1) ≥ 80% predicted, and were on inhaled corticosteroids with or without other controller asthma medications (e.g., long-acting β2-agonists [LABAs], leukotriene receptor antagonist [LTRA], or immunotherapy).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: omalizumab (Xolair); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a documented history of asthma as well as evidence of ≥ 12% reversibility of FEV1. Evidence of ≥ 12% reversibility of FEV1 may be obtained by any one of the following measures: 1) Documentation of ≥ 12% reversibility of FEV1 after albuterol administration at any time during the preceding 24 months; 2) Documentation of ≥ 12% improvement in FEV1 with two separate measurements obtained within a 4-week period surrounding an asthma exacerbation during the preceding 24 months; 3) Demonstration of ≥ 12%reversibility of FEV1 after albuterol administration at the time of screening
• Have baseline FEV1 ≥ 80% predicted normal value prior to randomization
• Have a positive skin test (diameter of wheal ≥ 3 mm vs. control) or in vitro radioallergosorbent test (RAST(R)) or ImmunoCap(R) to one relevant perennial aeroallergen such as cat or house dust mites documented within the previous year
• Be receiving at least an inhaled corticosteroid dosage of fluticasone dry powder inhaler (DPI) ≥ 200 ug/day or equivalent ex-valve dose during the 12 weeks prior to the screening visit
• During the 4-week run-in period prior to randomization, demonstrate evidence of inadequate asthma symptom control despite inhaled corticosteroids with or without other controller asthma medications (e.g., LABA, LTRA, immunotherapy). Inadequate asthma symptom control is defined as at least one of the following reported on the subject diary card during the 4-week run-in period: Daytime asthma symptoms as a score of ≥ 1 (scale of 0-4) on at least 20 of 28 days (missing data to be treated as a day with no symptoms) and a mean symptom score of ≥ 1.5 (mean will be calculated based on only data supplied; missing values will not be considered) or Nighttime awakening because of asthma symptoms (more than 4 times during the 4-week run-in period)
• Meet the study drug-dosing table eligibility criteria (serum baseline IgE level ≥ 30 to ≤ 1300 IU/mL and body weight ≥ 20 to ≤ 150 kg)
• If a female of childbearing potential, use an effective method of contraception (in the opinion of the investigator) to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study

Exclusion Criteria:

• Have received chronic systemic corticosteroids (oral or intravenous) within 3 months or have received a burst of oral corticosteroids within the last 2 weeks prior to screening
• Have received Xolair therapy at any time within 12 months prior to screening
• Are pregnant or lactating
• Have a known hypersensitivity to any ingredients of Xolair, including excipients (sucrose, histidine, polysorbate 20)
• Have a lifetime history of smoking > 10-pack years
• Have active lung disease other than asthma (e.g., chronic bronchitis, emphysema, cystic fibrosis, chronic obstructive pulmonary disease)
• Have a history of upper respiratory infection or lower respiratory infection within the 30 days prior to randomization
• Have a diagnosis of aspirin or nonsteroidal anti-inflammatory drug-induced asthma
• Have taken immunosuppressants or other investigational drugs within the 30 days prior to screening
• Have a significant medical illness other than asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab; Omalizumab (Xolair) administered in this study was either a minimum of 0.008 mg/kg/IgE [IU/mL] every 2 weeks or a minimum of 0.016 mg/kg/IgE [IU/mL] every 4 weeks.	Drug: omalizumab (Xolair); Omalizumab (Xolair) was administered subcutaneously every 2 or 4 weeks. The dose (mg) and dosing frequency were determined by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Assignment of the study drug dose was determined by using the study drug-dosing table. Doses of > 150 mg were divided among more than one injection site to limit injections to no more than 150 mg per site.
Placebo Comparator: Placebo; Placebo administered in this study was either a minimum of 0.008 mg/kg/IgE [IU/mL] every 2 weeks or a minimum of 0.016 mg/kg/IgE [IU/mL] every 4 weeks.	Drug: placebo; The dose of placebo consisting of sucrose, L-histidine, L-histidine hydrochloride monohydrate, and polysorbate 20 was administered by subcutaneous injection every 2 or 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Asthma Exacerbations Over the 24 Week Treatment Period	A protocol-defined asthma exacerbation was a worsening of asthma requiring treatment with oral or intravenous corticosteroid burst and/or a doubling of the baseline inhaled corticosteroids (ICS) dose for at least 3 days. The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 24 week treatment period in each treatment group.	Start of treatment to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing One or More Protocol-defined Asthma Exacerbations During the Treatment Period	The number of patients reporting one or more protocol-defined asthma exacerbations during the 24 week treatment period. A protocol-defined asthma exacerbation was a worsening of asthma requiring treatment with oral or intravenous corticosteroid burst and/or a doubling of the baseline inhaled corticosteroids (ICS) dose for at least 3 days.	Start of treatment to 24 weeks
Change From Baseline in Nocturnal and Daytime Asthma Symptom Scores at Week 24	The daytime asthma symptom score assessed the symptoms: shortness of breath, chest discomfort, wheezing, and cough over the previous 24 hour period on a scale of 0(no symptoms) to 4(marked discomfort). The nocturnal asthma score was the patient's response to:How did you sleep last night? rated on a scale of 0(no problems) to 4(difficulty sleeping;rescue medicine used). Scores were collected daily. Change from Baseline (mean of last 28 days prior to first dosing date) at Week 24 (mean of last 28 days prior to week 24 visit). A negative change from baseline score indicates improvement.	Baseline and 24 weeks
Relative Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24	Spirometry was used to assess FEV1. All spirometry measurements were performed in accordance with the American Thoracic Society (ATS) guidelines. The relative percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was calculated at week 24 using the formula: (FEV1 at week 24 - FEV1 at baseline) / FEV1 at baseline * 100 for each treatment group.	Baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Karin Rosen, MD, PhD, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2006
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: November 17, 2004
• First Submitted That Met QC Criteria: November 17, 2004
• First Posted (Estimate): November 18, 2004

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Atopic Asthma; Omalizumab (Xolair)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: Q2982g