Allergic Asthma
Conditions
Keywords
AQUA, anti-CD11, CD11a, Asthma, Allergy
Brief summary
This was a multicenter, randomized, double-blind, parallel-group, three-arm, placebo-controlled study designed to demonstrate the efficacy of two different formulations of omalizumab compared with placebo in reducing the airway reaction to an inhaled aeroallergen solution in adult subjects with mild allergic asthma.
Interventions
DRUGomalizumab
Aged Liquid; subcutaneous repeating dose
DRUGplacebo
Subcutaneous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Meet criteria for the diagnosis of allergic asthma * Be between the ages of 18 to 65 years * Have a normal chest X-ray within 2 years of screening
Exclusion criteria
* Need daily controller medication for asthma * History of hypersensitivity to the study drug or to drugs with similar chemical structures or to any ingredients, including excipients of the study medication or drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma globulin) * Have a documented medical history of anaphylaxis * Have lung disease other than mild allergic asthma * Have taken other investigational drugs within 30 days or 5 half-lives prior to the screening visit, whichever is longer * Are unable or unwilling to comply with study procedures and visits * Are pregnant or lactating * Have significant medical illness other than asthma, including malignancies, parasitic infections, immune system disorders, and thrombocytopenia * Have been treated with omalizumab within 12 months prior to screening * Currently smoke or have a history of smoking more than 10 pack-years * Have a history of drug or alcohol abuse, which, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1) | From baseline to Week 16 | The primary analysis included two tests: a test for superiority of the lyophilized formulation of omalizumab compared with placebo in the change of allergen concentration and a test for the superiority of the aged liquid omalizumab compared with placebo. The difference for the change in the allergen concentration between the lyophilized formulation of omalizumab and placebo, and between the aged liquid omalizumab and placebo were assessed by the exact Wilcoxon-Mann-Whitney test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge | From baseline to Week 16 | FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity, measured in liters. The allergen FEV1 two-point slope is defined as the final percent change in FEV1 from pre-challenge value divided by the final value of allergen concentration used in the challenge. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liquid Omalizumab Liquid omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening | 23 |
| Lyopholized Omalizumab Lyophilized omalizumab subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening | 24 |
| Placebo Lyophilized placebo subcutaneously either every 2 weeks or every 4 weeks based on their weight and IgE levels at screening | 14 |
| Total | 61 |
Baseline characteristics
| Characteristic | Total | Liquid Omalizumab | Lyopholized Omalizumab | Placebo |
|---|---|---|---|---|
| Age, Continuous | 30.1 years STANDARD_DEVIATION 11.1 | 28.5 years STANDARD_DEVIATION 10.3 | 30.6 years STANDARD_DEVIATION 12.8 | 32.0 years STANDARD_DEVIATION 9.6 |
| Age, Customized 18 to 40 years | 50 participants | 18 participants | 21 participants | 11 participants |
| Age, Customized 41 to 65 years | 9 participants | 5 participants | 1 participants | 3 participants |
| Age, Customized > 65 years | 2 participants | 0 participants | 2 participants | 0 participants |
| Sex: Female, Male Female | 28 Participants | 10 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 33 Participants | 13 Participants | 16 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 23 | 6 / 24 | 5 / 14 |
| serious Total, serious adverse events | 0 / 23 | 2 / 24 | 0 / 14 |
Outcome results
Primary
Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1)
The primary analysis included two tests: a test for superiority of the lyophilized formulation of omalizumab compared with placebo in the change of allergen concentration and a test for the superiority of the aged liquid omalizumab compared with placebo. The difference for the change in the allergen concentration between the lyophilized formulation of omalizumab and placebo, and between the aged liquid omalizumab and placebo were assessed by the exact Wilcoxon-Mann-Whitney test.
Time frame: From baseline to Week 16
Population: Modified intent-to-treat (ITT) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liquid Omalizumab | Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1) | 1.15 concentration change |
| Lyopholized Omalizumab | Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1) | 1.85 concentration change |
| Placebo | Change in Logarithmically Transformed (log2) Allergen PC15 Concentration (Allergen Concentration Required to Evoke a 15% Decrease in FEV1) | 0.36 concentration change |
p-value: 0.13Wilcoxon (Mann-Whitney)
p-value: 0.0133Wilcoxon (Mann-Whitney)
Secondary
Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge
FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity, measured in liters. The allergen FEV1 two-point slope is defined as the final percent change in FEV1 from pre-challenge value divided by the final value of allergen concentration used in the challenge.
Time frame: From baseline to Week 16
Population: Modified ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liquid Omalizumab | Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge | 0.52 ratio of FEV1 |
| Lyopholized Omalizumab | Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge | 0.29 ratio of FEV1 |
| Placebo | Ratio of the Allergen Forced Expiratory Volume at One Second (FEV1) Two-point Slope at the Week 16 Allergen Challenge to the Allergen FEV1 Two-point Slope at the Baseline Allergen Challenge | 0.95 ratio of FEV1 |
p-value: 0.09Wilcoxon (Mann-Whitney)
p-value: 0.0028Wilcoxon (Mann-Whitney)