Asthma
Conditions
Keywords
Xolair, Allergic asthma, Cat allergy
Brief summary
This was a 3-center, randomized, double-blind, parallel-group, placebo-controlled study with a 16-week treatment phase to determine whether subcutaneous omalizumab, compared with placebo, reduces the degree of bronchoconstriction induced by environmental cat dander exposure in patients 18-65 years old with stable, moderate asthma and a history of cat dander-induced asthma symptoms.
Detailed description
A cat dander allergen challenge model was used to collect data for all of the Outcome Measures. The cat allergen levels in the model are similar to those found in homes with cats and are capable of inducing lower- and upper-airway responses that have been used to assess the efficacy of several asthma and allergy therapies. Cat allergen exposure was performed in a room furnished with upholstered furniture, a blanket, and a cat litter box. The door was kept closed at all times, except when personnel or study patients were entering or leaving the room. The ventilation system was operating at all times except during cat allergen challenges. Two neutered adult cats were kept in the room at all times and were free to move about except during challenges, at which time they are placed in wire cages. Immediately before a challenge, the blanket was shaken vigorously to distribute cat allergen throughout the room.
Interventions
DRUGOmalizumab
Omalizumab was supplied as a sterile, white, preservative-free, lyophilized powder in single-use vials that was reconstituted with sterile water for injection.
DRUGPlacebo
Placebo contained the same ingredients as the omalizumab formulation, excluding omalizumab.
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. * 18 to 65 years of age and in general good health. * History of moderate asthma, defined by the need for routine inhaled corticosteroids for at least the last 90 days prior to screening as well as the routine use of additional medication(s) (eg, short- or long-acting β2-agonists, leukotriene antagonist, or theophylline) to control asthma symptoms. * History of cat dander-induced asthma in the 3 years prior to randomization. * Cat exposure at the time of screening must remain constant throughout the duration of the study (eg, patients having cat exposure at home must continue to have regular exposure during the study; patients having no cat exposure at home must continue having no exposure at home during the study). * Positive skin test to cat allergen, defined as a ≥ 5 mm wheal over the saline control wheal. * Baseline forced expiratory volume in 1 second (FEV1) ≥ 70% predicted after withholding long-acting β2-agonists for \> 36 hours and short-acting β2-agonists for \> 6 hours. * Eligibility per the study drug dosing table (serum IgE level ≥ 30 to ≤ 700 IU/mL and body weight ≥ 30 to ≤ 150 kg) and ability to be dosed per the dosing table. * Less than 10 pack-years of smoking history. * Demonstrated ≥ 20% fall in FEV1 during up to 1 hour of exposure in the cat environmental exposure chamber and ability to withstand exposure for at least 20 minutes.
Exclusion criteria
* Unstable asthma (defined as a hospitalization within the prior 6 months or an exacerbation requiring oral corticosteroids within 4 weeks of study entry). * Life-threatening episode of asthma in the previous year. * History of severe allergic reactions to cat exposure. * Having undergone cat immunotherapy within 6 months prior to screening. * Upper respiratory infection within 2 weeks of study entry. * Active lung disease other than asthma. * Significant medical illness other than asthma, including malignancies, parasitic infections, immune system disorders, and thrombocytopenia. * 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 (eg, monoclonal antibodies, polyclonal gamma globulin). * Documented medical history of anaphylaxis. * Receipt of other investigational drugs within 30 days or 5 half-lives prior to screening, whichever is longer. * Pregnant women and nursing mothers. * Treatment with omalizumab within 12 months prior to screening. * History of drug or alcohol abuse that, in the judgment of the investigator, may put the patient at risk for being unable to participate fully in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Over a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | Week 16 | Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of the baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Forced Expiratory Volume in 1 Second (FEV1) at 20 Minutes of a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | Week 16 | Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure. |
| Maximum Percent Change in Forced Expiratory Volume in 1 Second (FEV1) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | Week 16 | Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure. |
| Area Under the Curve (AUC) of Change in Chest Symptom Score During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | Week 16 | The chest symptom score was defined as the total of 4 sub-scores: Chest tightness, wheezing, shortness of breath, and cough. Each sub-score was rated by the patient on a scale of 0-3 (0=none, 1=mild, 2=moderate, and 3=severe) immediately prior to and approximately every 5 minutes during chamber exposure. The maximum chest symptom score was 12 points. A lower score indicates a reduced response to the allergen exposure and fewer respiratory symptoms. |
| Area Under the Curve (AUC) of Change in Nasal-ocular Symptom Score (NOSS) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | Week 16 | The NOSS was defined as the total of 4 sub-scores: Nasal congestion, rhinorrhea, nasal pruritus, ocular pruritus, and ocular tearing. Each sub-score was rated by the patient on a scale of 0-3 (0=none, 1=mild, 2=moderate, and 3=severe) immediately prior to and approximately every 5 minutes during chamber exposure. The maximum NOSS was 15 points. A lower score indicates a reduced response to the allergen exposure and fewer nasal-ocular symptoms. |
| Duration of Allergen Exposure During the Cat Allergen Exposure Challenge at Week 16 | Week 16 | The challenge was stopped if a patient stated that they were extremely uncomfortable and would like to leave the room, the FEV1 has decreased by 50% from the baseline value, or after 60 minutes of exposure. The duration of allergen exposure was the time from when the patient entered the exposure room until the challenge stopped, with a maximum of 60 minutes. A longer duration indicates greater tolerance of the allergen exposure. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Patients received omalizumab via subcutaneous injection either every 2 weeks or every 4 weeks for 16 weeks. The dose administered and the dosing interval were determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table. | 36 |
| Placebo Patients received placebo as a subcutaneous injection either every 2 weeks or every 4 weeks for 16 weeks. Patients received injections at the same time intervals as the omalizumab group. | 33 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Subject's Decision to Withdraw | 3 | 0 |
Baseline characteristics
| Characteristic | Omalizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.6 years STANDARD_DEVIATION 10.5 | 38.5 years STANDARD_DEVIATION 12.3 | 36.5 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 21 Participants | 22 Participants | 43 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 36 | 31 / 33 |
| serious Total, serious adverse events | 0 / 36 | 0 / 33 |
Outcome results
Primary
Area Under the Curve (AUC) of Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Over a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16
Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of the baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Area Under the Curve (AUC) of Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Over a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 15.03 Percent change from pre-challenge*hours | Standard Deviation 15.9 |
| Placebo | Area Under the Curve (AUC) of Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Over a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 27.80 Percent change from pre-challenge*hours | Standard Deviation 15.28 |
Secondary
Area Under the Curve (AUC) of Change in Chest Symptom Score During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16
The chest symptom score was defined as the total of 4 sub-scores: Chest tightness, wheezing, shortness of breath, and cough. Each sub-score was rated by the patient on a scale of 0-3 (0=none, 1=mild, 2=moderate, and 3=severe) immediately prior to and approximately every 5 minutes during chamber exposure. The maximum chest symptom score was 12 points. A lower score indicates a reduced response to the allergen exposure and fewer respiratory symptoms.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Area Under the Curve (AUC) of Change in Chest Symptom Score During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 2.205 Units on a scale*hours | Standard Deviation 2.066 |
| Placebo | Area Under the Curve (AUC) of Change in Chest Symptom Score During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 5.602 Units on a scale*hours | Standard Deviation 2.873 |
Secondary
Area Under the Curve (AUC) of Change in Nasal-ocular Symptom Score (NOSS) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16
The NOSS was defined as the total of 4 sub-scores: Nasal congestion, rhinorrhea, nasal pruritus, ocular pruritus, and ocular tearing. Each sub-score was rated by the patient on a scale of 0-3 (0=none, 1=mild, 2=moderate, and 3=severe) immediately prior to and approximately every 5 minutes during chamber exposure. The maximum NOSS was 15 points. A lower score indicates a reduced response to the allergen exposure and fewer nasal-ocular symptoms.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Area Under the Curve (AUC) of Change in Nasal-ocular Symptom Score (NOSS) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 2.448 Units on a scale*hours | Standard Deviation 1.72 |
| Placebo | Area Under the Curve (AUC) of Change in Nasal-ocular Symptom Score (NOSS) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 5.192 Units on a scale*hours | Standard Deviation 3.141 |
Secondary
Duration of Allergen Exposure During the Cat Allergen Exposure Challenge at Week 16
The challenge was stopped if a patient stated that they were extremely uncomfortable and would like to leave the room, the FEV1 has decreased by 50% from the baseline value, or after 60 minutes of exposure. The duration of allergen exposure was the time from when the patient entered the exposure room until the challenge stopped, with a maximum of 60 minutes. A longer duration indicates greater tolerance of the allergen exposure.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omalizumab | Duration of Allergen Exposure During the Cat Allergen Exposure Challenge at Week 16 | 50 Minutes |
| Placebo | Duration of Allergen Exposure During the Cat Allergen Exposure Challenge at Week 16 | 22 Minutes |
Secondary
Maximum Percent Change in Forced Expiratory Volume in 1 Second (FEV1) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16
Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Maximum Percent Change in Forced Expiratory Volume in 1 Second (FEV1) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 21.07 Percent change | Standard Deviation 17.68 |
| Placebo | Maximum Percent Change in Forced Expiratory Volume in 1 Second (FEV1) During a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 33.52 Percent change | Standard Deviation 16.03 |
Secondary
Percent Change in Forced Expiratory Volume in 1 Second (FEV1) at 20 Minutes of a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16
Spirometry was performed prior to chamber exposure, approximately every 10 minutes during exposure, and approximately every 20 minutes after exposure until FEV1 returned to within 10% of baseline value. A smaller change in FEV1 indicates a reduced response to the allergen exposure.
Time frame: Week 16
Population: Modified intent-to-treat population: All randomized patients that received at least 1 dose of study drug and who had at least 1 primary efficacy data point, ie, at least 1 FEV1 measurement during the 1-hour cat allergen exposure at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Percent Change in Forced Expiratory Volume in 1 Second (FEV1) at 20 Minutes of a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 15.28 Percent change | Standard Deviation 18 |
| Placebo | Percent Change in Forced Expiratory Volume in 1 Second (FEV1) at 20 Minutes of a 1-hour Cat Allergen Exposure From Pre-challenge at Week 16 | 29.97 Percent change | Standard Deviation 17.77 |