Asthma
Conditions
Keywords
Asthma, omalizumab, safety, allergic asthma, adolescents
Brief summary
The primary objective of this study is to assess the immunogenic potential of the liquid formulation of omalizumab administered over a period of 6 months in moderate to severe persistent allergic asthma patients 12 years of age or older, with no previous exposure to the drug (omalizumab naïve patients). The secondary objective of this study is to assess the safety of the liquid formulation of omalizumab in the same patients.
Interventions
DRUGomalizumab
The liquid formulation of omalizumab was packaged in a pre-filled safety syringe containing either 75 mg (0.5ml) or 150 mg (1.0 ml) of drug. The syringes were clearly marked so that the health care provider could differentiate between the 75 mg or 150 mg syringe.
Sponsors
Genentech, Inc.
Tanox
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 12 years old or above with moderate to severe allergic asthma * Body weight greater than 30kg and less than 150 kg and total serum IgE level greater than 30 to less than 700 IU/ml * Diagnosis of allergic asthma greater than 1 year duration, according to the American Thoracic Society criteria (14) and at screening, a history consistent with clinical features of moderate to severe persistent asthma. * Positive skin prick test (diameter of wheel is greater than 3mm) to at least one perennial allergen within the previous one year to visit 1, to which the patient will be exposed on a regular basis (most days) for the duration of the study. * No clinically significant asthma exacerbations that required treatment with systemic corticosteroids during the four weeks immediately prior to screening visit (Visit 1) and during screening period (between Visit 1 and 2) * Demonstrated evidence of inadequate asthma symptom control, despite treatment with ICS according to clinical features of moderate to severe persistent asthma.
Exclusion criteria
* Previous exposure to omalizumab * Previous exposure to other humanized proteins or monoclonal antibodies * Known HAHA to other monoclonal antibodies * History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures * Known hypersensitivity to any ingredients, including excipients of the study medication or drugs related to omalizumab (e.g. monoclonal antibodies, polyclonal gamma globulin) * Active lung disease other than allergic asthma (e.g. cystic fibrosis, bronchiectasis) * Elevated serum IgE levels for reasons other than allergy (e.g. parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | 16 weeks after last dose | An assessment of the immunogenic potential of omalizumab liquid was a primary objective of the study, and was based on the results of the human anti-human antibody (HAHA) assays at the end of the follow-up period. A participant was considered potentially HAHA positive if either Fab or Fc was more than 2.0 titer. All values more than 2.0 titer were re-assayed to obtain a confirmatory result. Confirmatory results were used to determine those participants who were HAHA positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | 24 weeks treatment period + 4 weeks for following up participants | The assessment of safety was based on the number of patients with AEs (mild, moderate and severe) and SAEs. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above. The duration of the treatment period was 24 weeks, but patients were followed for an additional 4 weeks, so that the total duration of the treatment period for purposes of AE reporting was 28 weeks. |
| Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Last 12 weeks of the follow-up period (initial 4 weeks of the follow-up period were included in the treatment period for AE reporting) | The assessment of safety was based on the number of patients with AEs (mild, moderate and severe) and SAEs. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above. The duration of the follow-up period was 16 weeks, but for purposes of AE reporting the follow-up period was 12 weeks (as the first 4 weeks of follow-up were included in the treatment period). |
Countries
Argentina, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab The determined dose was injected subcutaneously every 2 weeks or every 4 weeks. Dose and dosing interval were determined based on patient body weight and pre-treatment serum IgE level; a dosing table was used. | 155 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up Period (16 Weeks) | Administrative problems | 1 |
| Follow-up Period (16 Weeks) | Adverse Event | 1 |
| Follow-up Period (16 Weeks) | Death | 1 |
| Follow-up Period (16 Weeks) | Lost to Follow-up | 3 |
| Follow-up Period (16 Weeks) | Missing | 3 |
| Follow-up Period (16 Weeks) | Protocol Deviation | 1 |
| Follow-up Period (16 Weeks) | Subject withdrew consent | 2 |
| Treatment Period (24 Weeks) | Administrative problems | 2 |
| Treatment Period (24 Weeks) | Adverse Event | 4 |
| Treatment Period (24 Weeks) | Lost to Follow-up | 2 |
| Treatment Period (24 Weeks) | Protocol Deviation | 5 |
| Treatment Period (24 Weeks) | Subject withdrew consent | 1 |
| Treatment Period (24 Weeks) | Unsatisfactory therapeutic effect | 1 |
Baseline characteristics
| Characteristic | Omalizumab |
|---|---|
| Age, Categorical <=18 years | 13 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants |
| Age Continuous | 42.7 years STANDARD_DEVIATION 14.32 |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 74 / 155 | 34 / 148 |
| serious Total, serious adverse events | 14 / 155 | 1 / 148 |
Outcome results
Primary
The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period
An assessment of the immunogenic potential of omalizumab liquid was a primary objective of the study, and was based on the results of the human anti-human antibody (HAHA) assays at the end of the follow-up period. A participant was considered potentially HAHA positive if either Fab or Fc was more than 2.0 titer. All values more than 2.0 titer were re-assayed to obtain a confirmatory result. Confirmatory results were used to determine those participants who were HAHA positive.
Time frame: 16 weeks after last dose
Population: The Safety Population consisted of all patients that received any part of a dose of study drug and had any post-baseline assessment, whether scheduled or not. The analysis was done on total number of patients who had follow-up HAHA sample taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fab HAHA Positive - Positive at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fc HAHA Positive - Positive at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fc HAHA Positive - Missing at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fab HAHA Positive - Negative at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fab HAHA Positive - Missing at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fc HAHA Positive - Negative at baseline | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Fab and/or Fc HAHA Positive - Fab and Fc HAHA -Ve | 0 participants |
| Follow-up Period | The Number of Participants With Confirmed Positive Human Antihuman Antibody (HAHA) Results at the End of the 16-week Follow-up Period | Missing at baseline | 0 participants |
Secondary
Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period
The assessment of safety was based on the number of patients with AEs (mild, moderate and severe) and SAEs. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above. The duration of the follow-up period was 16 weeks, but for purposes of AE reporting the follow-up period was 12 weeks (as the first 4 weeks of follow-up were included in the treatment period).
Time frame: Last 12 weeks of the follow-up period (initial 4 weeks of the follow-up period were included in the treatment period for AE reporting)
Population: The safety population consisted of all patients that received any part of a dose of study drug and had any post-baseline assessment, whether scheduled or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Severe AEs | 3 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | AEs suspected to be related to study drug | 0 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | AEs not suspected to be related to study drug | 51 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Deaths | 0 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Participants with AEs during the follow-up period | 51 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Mild AEs | 11 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Moderate AEs | 37 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Serious adverse events (SAEs) | 1 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Discontinued due to Adverse Events | 1 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Discontinued due to Serious Adverse Events | 0 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Follow-up Period | Discontinued due to non-serious Adverse Events | 1 participants |
Secondary
Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period
The assessment of safety was based on the number of patients with AEs (mild, moderate and severe) and SAEs. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above. The duration of the treatment period was 24 weeks, but patients were followed for an additional 4 weeks, so that the total duration of the treatment period for purposes of AE reporting was 28 weeks.
Time frame: 24 weeks treatment period + 4 weeks for following up participants
Population: The safety population consisted of all patients that received any part of a dose of study drug and had any post-baseline assessment, whether scheduled or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | AEs suspected to be related to study drug | 22 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | AEs not suspected to be related to study drug | 102 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Deaths | 1 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Serious Adverse Events (SAEs) | 14 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Participants with AEs during the treatment period | 124 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Mild AEs | 25 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Moderate AEs | 76 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Severe AEs | 23 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Discontinued due to Adverse Events | 4 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Discontinued due to Serious Adverse Events | 2 participants |
| Follow-up Period | Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period | Discontinued due to non-serious Adverse Events | 2 participants |