Asthma
Conditions
Keywords
Asthma, allergen challenge, bronchoprovocation, Methacholine challenge, serum Immunoglobulin E, Nitric Oxide, skin prick test
Brief summary
This study was intended to demonstrate that patients with standard and high immunoglobulin E (IgE) levels can be protected from allergen induced broncho-constriction by Xolair
Interventions
DRUGXolair
Xolair (Omalizumab) dose: 2 x 450 mg, 2 x 525 mg or 2 x 600 mg; subcutaneous injection;
DRUGPlacebo
Matching placebo of Xolair (omalizumab), by subcutaneous injection of a solution with a concentration of 125 mg/mL in a supine position.
Sponsors
Genentech, Inc.
Tanox
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female adult patients, body weight between 40-150 kg aged 18-65 years (inclusive) * Patients diagnosed with asthma with Forced Expiratory Volume (FEV1) ≥65% of the predicted normal value for the patient * Positive skin prick test to a specific allergen * Patients had to demonstrate a Provocative Dose 20% FEV1 decline (PD20) response to an aeroallergen in the graded allergen bronchoprovocation testing (ABP) at screening
Exclusion criteria
* Current active smokers * Patients who have been hospitalized or had emergency treatment for an asthma attack in the 12 months prior to study start * History of bleeding disorders * History of drug allergy * Pregnant women or nursing mothers * Females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception (surgical contraception or double barrier methods (to be continued for at least two months following last dose) are acceptable). * Sexually active males who have not been sterilized and are not using a condom * History of immunocompromise, including a positive HIV * A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. * History of drug or alcohol abuse within 12 months of study start Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8, Week 16 | The EAR was defined as the maximum percent drop in forced expiratory volume in one second (FEV1) in the first 30 minutes after the challenge: EAR = 100\* \[ FEV1 (0) - Minimum FEV1 (10, 15, 30 min)\] / FEV1 (0). For FEV1 (0), the best post saline (Control) FEV1 was used. The EAR was analyzed using a linear (ANCOVA) model with a fixed effect for treatment groups and the EAR from the baseline challenge was used as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 0, Week 8 and Week 16 | Late-phase allergic response (LAR) was only determined for those patients who had an LAR \>= 15% at baseline allergen bronchoprovocation testing. For Forced Expiratory Volume, FEV1 (0), the best post saline (Control) FEV1 was used. LAR (%) = 100\*\[FEV1 (0) - Minimum FEV1 (3-8h)\]/FEV1 (0). |
Countries
Germany, Netherlands, South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) Patients with screening Immunoglobulin E (IgE) levels = 30-300 IU/mL. Participants received subcutaneous injections of Xolair (Omalizumab) every 2 weeks or every 4 weeks; dosage dependent on IgE level and body weight. | 18 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) Patients with screening Immunoglobulin E (IgE) levels = 700- 2000 IU/mL. Participants received subcutaneous injections of Xolair (Omalizumab) every 2 weeks; dosage dependent on IgE level and body weight. | 16 |
| Xolair (Immunoglobulin E (IgE) = 301- 699 IU/mL) Patients with screening Immunoglobulin E (IgE) levels = 301- 699 IU/mL. Participants received subcutaneous injections of Xolair (Omalizumab) every 2 weeks; dosage dependent on IgE level and body weight. | 10 |
| Placebo Comparator By subcutaneous injection of a solution with a concentration of 125 mg/mL placebo in a supine position: Patients in Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) group received doses of 150 mg to 375 mg of placebo every 2 or 4 weeks for 12 or 14 weeks. Patients in Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) group received doses of 450 mg, 525 mg, or 600 mg of placebo every 2 weeks for 14 weeks. Patients in Xolair (Immunoglobulin E (IgE) = 301- 699 IU/mL) group received doses of 225 mg to 375 mg of placebo every 2 weeks for 6 weeks. | 16 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Abnormal Laboratory Value | 2 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Xolair (Immunoglobulin E (IgE) = 301- 699 IU/mL) | Placebo Comparator | Total |
|---|---|---|---|---|---|
| Age Continuous | 36 years STANDARD_DEVIATION 11.9 | 29 years STANDARD_DEVIATION 11 | 26 years STANDARD_DEVIATION 6 | 34 years STANDARD_DEVIATION 10.4 | 32 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 4 Participants | 7 Participants | 26 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 6 Participants | 9 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 18 | 15 / 16 | 6 / 10 | 12 / 16 |
| serious Total, serious adverse events | 1 / 18 | 1 / 16 | 0 / 10 | 0 / 16 |
Outcome results
Primary
Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients
The EAR was defined as the maximum percent drop in forced expiratory volume in one second (FEV1) in the first 30 minutes after the challenge: EAR = 100\* \[ FEV1 (0) - Minimum FEV1 (10, 15, 30 min)\] / FEV1 (0). For FEV1 (0), the best post saline (Control) FEV1 was used. The EAR was analyzed using a linear (ANCOVA) model with a fixed effect for treatment groups and the EAR from the baseline challenge was used as a covariate.
Time frame: Week 8, Week 16
Population: Safety and Pharmacodynamic (PD) population. Although all patients had baseline EAR not all of them had a value determined for week 8 and 16 reducing the number evaluable for analysis particularly at week 8. Patients of first 2 Xolair groups received placebo treatment were pooled in one placebo group for analysis. No analysis on third Xolair groups.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=12, 12, 13) | 9.3 Percentage of EAR | Standard Error 3.97 |
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=14, 15, 15) | 11.8 Percentage of EAR | Standard Error 3.81 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=12, 12, 13) | 5.6 Percentage of EAR | Standard Error 2.07 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=14, 15, 15) | 5.1 Percentage of EAR | Standard Error 2.02 |
| Placebo Comparator | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=12, 12, 13) | 23.1 Percentage of EAR | Standard Error 3.57 |
| Placebo Comparator | Early Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=14, 15, 15) | 20.0 Percentage of EAR | Standard Error 2.43 |
Secondary
Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients
Late-phase allergic response (LAR) was only determined for those patients who had an LAR \>= 15% at baseline allergen bronchoprovocation testing. For Forced Expiratory Volume, FEV1 (0), the best post saline (Control) FEV1 was used. LAR (%) = 100\*\[FEV1 (0) - Minimum FEV1 (3-8h)\]/FEV1 (0).
Time frame: Week 0, Week 8 and Week 16
Population: Safety and Pharmacodynamic (PD) population. Although all patients had baseline EAR not all of them had a value determined for week 8 and 16 reducing the number evaluable for analysis particularly at week 8. Patients of first 2 Xolair groups received placebo treatment were pooled in one placebo group for analysis. No analysis on third Xolair groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=6, 1, 3) | 5.3 Percentage of LAR | Standard Deviation 12.13 |
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 0 (n=8, 3, 5) | 22.5 Percentage of LAR | Standard Deviation 6.12 |
| Xolair (Immunoglobulin E (IgE) = 30-300 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=7, 2, 4) | 0.23 Percentage of LAR | Standard Deviation 7.109 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=6, 1, 3) | -3.5 Percentage of LAR | Standard Deviation 0 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 0 (n=8, 3, 5) | 25.7 Percentage of LAR | Standard Deviation 12.62 |
| Xolair (Immunoglobulin E (IgE) = 700- 2000 IU/mL) | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=7, 2, 4) | 1.5 Percentage of LAR | Standard Deviation 1.53 |
| Placebo Comparator | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 0 (n=8, 3, 5) | 27.4 Percentage of LAR | Standard Deviation 7.27 |
| Placebo Comparator | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 16 (n=7, 2, 4) | 12.3 Percentage of LAR | Standard Deviation 7.09 |
| Placebo Comparator | Late Phase Allergic Response After Treatment With Study Drug in Active and Placebo Patients | Week 8 (n=6, 1, 3) | 19.1 Percentage of LAR | Standard Deviation 13.42 |