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)

NCT00096954 | Completed Phase 4 Results

• 1 other identifier: Q2982g
• Study Type: interventional
• Target: 333
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Asthma

Keywords

Omalizumab (Xolair); Atopic Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants Experiencing One or More Protocol-defined Asthma Exacerbations During the Treatment Period

  Start of treatment to 24 weeks

• Change From Baseline in Nocturnal and Daytime Asthma Symptom Scores at Week 24

  Baseline and 24 weeks

• Relative Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24

  Baseline and 24 weeks

Study Arms (2)

Omalizumab

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

omalizumab (Xolair) DRUG

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.

Omalizumab

placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Conditions

Asthma

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Limitations and Caveats

This is a stand-alone study to fulfill one of the post-marketing commitments.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Karin Rosen, MD, PhD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2004
• First Posted: November 18, 2004
• Study Start: February 1, 2006
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 14, 2017
• Results First Posted: December 8, 2011

Record last verified: 2017-05