Asthma, Healthy
Conditions
Keywords
Xolair, Asthma, Skin Tests
Brief summary
This study enrolled 30 healthy volunteers and 30 patients with atopic asthma, for a total of 60 subjects. The study examined the tolerability of omalizumab and omalizumab excipients in two successive cohorts of subjects, healthy volunteers and patients with allergic asthma without prior exposure to omalizumab, according to a skin test protocol, consisting of a prick skin test and/or intradermal test.
Interventions
DRUGCohort I
In sterile water for injection (SWFI), full concentration and 1:1000, 1:100, 1:10 dilutions of 125 mg/mL of standard solution of omalizumab and its excipients. Skin prick test of each dilution concentration of 1:1000, 1:100, 1:10 and full concentration and Intradermal tests of each dilution concentration of 1:1000, 1:100 and 1:10 were followed by 20 minutes of observation. For the skin prick test, participants were tested initially with positive control (histamine 6 mg/mL) and negative control (saline), and with omalizumab and its excipients simultaneously from the lowest concentration. For the intradermal test, participants were tested initially with positive control (histamine 0.1 mg/mL) and negative control (saline), and with omalizumab and its excipients simultaneously from the lowest concentration. Dilutions of omalizumab and its excipients were in SWFI.
DRUGCohort 2
In a saline solution, full concentration and 1:1000, 1:100, 1:10 dilutions of 125 mg/mL of standard solution of omalizumab and its excipients. Skin prick test of each dilution concentration of 1:1000, 1:100, 1:10 and full concentration and Intradermal tests of each dilution concentration of 1:100,000 and 1:10,000 were followed by 20 minutes of observation. For the skin prick test, participants were tested initially by positive control (histamine 6 mg/mL) and negative control (saline), and with omalizumab and its excipients simultaneously from the lowest concentration. For the intradermal test, participants were tested initially with positive control (histamine 0.1 mg/mL) and negative control (saline), and with omalizumab and its excipients simultaneously from the lowest concentration. Dilutions of omalizumab and its excipients were made in saline.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* (Applicable to healthy subjects only) Healthy subjects not taking any regular prescription medication, without history of allergy, and considered healthy by the physician * (Applicable to asthma patients only) Patients with atopic asthma diagnosed by a physician with asthma and history of positive skin test(s) * Physical examination findings within normal limits * Body mass index (BMI) between 18 and 30, inclusive
Exclusion criteria
* Pregnancy and lactation * Current or previous treatment with a biologic agent (e.g., monoclonal antibody) * Concurrent disease or condition that would interfere, or for which the treatment might interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to individuals in this study * History or symptoms of significant psychiatric disease, including but not limited to, depression, schizophrenia, etc. * History of drug abuse * Participation in an investigational drug or device trial within the last 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants by of Adverse Events Following a Skin Test Procedure | Up to 7 days following skin testing | Skin test procedures were skin prick test or intradermal test. The test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped. Subjects were observed for 20 minutes following each test; subjects were observed for 1 hour after the last intradermal test. Those with a positive response were observed for an additional 6 hours. Severity refers to the intensity of an AE (mild, moderate or severe). Mild is itching or hives, for example. A severe event requires emergency medical treatment and can result in death. |
| Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | on the day of skin test | For skin prick, positive control (histamine 6 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The skin prick test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped. |
| Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | on the day of skin test | For intradermal testing, positive control (histamine 0.1 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The intradermal test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped. |
| Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) | on the day of skin test | For intradermal testing, positive control (histamine 0.1 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The intradermal test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Subjects Healthy participants were tested sequentially in a skin prick test procedure with positive control (histamine 6 mg/mL), negative control (saline), and 1:1000, 1:100, 1:10 dilution and full concentrations of both omalizumab and omalizumab excipients. Without reaction, this then followed a sequential intradermal test procedure with positive control (histamine 0.1 mg/mL), negative control (saline), and 1:1000, 1:100 and 1:10 dilution concentrations of omalizumab and its excipients. There was a 20 minute observation period following all dosings.
Excipients include sucrose, histidine, histidine hydrochloride monohydrate and polysorbate 20.
Dilutions of omalizumab and its excipients were made in sterile water for injection (SWFI). | 30 |
| Allergic Asthma Participants Allergic asthma participants were tested sequentially in a skin prick test procedure with positive control (histamine 6 mg/mL), negative control (saline), and a succession of 1:1000, 1:100, 1:10 dilutions and full concentration of both omalizumab and omalizumab excipients. Without reaction, this then followed a sequential intradermal test procedure with positive control (histamine 0.1 mg/mL), negative control (saline), and 1:100,000 and 1:10,000 dilution concentrations of omalizumab and its excipients. There was a 20 minute observation period following all dosings.
Excipients include sucrose, histidine, histidine hydrochloride monohydrate and polysorbate 20.
Dilutions of omalizumab and its excipients were made in saline solution. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Healthy Subjects | Allergic Asthma Participants | Total |
|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 13.1 | 32.0 years STANDARD_DEVIATION 10.88 | 32.9 years STANDARD_DEVIATION 11.97 |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 24 Participants |
| Sex: Female, Male Male | 23 Participants | 13 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 30 | 3 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Number of Participants by of Adverse Events Following a Skin Test Procedure
Skin test procedures were skin prick test or intradermal test. The test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped. Subjects were observed for 20 minutes following each test; subjects were observed for 1 hour after the last intradermal test. Those with a positive response were observed for an additional 6 hours. Severity refers to the intensity of an AE (mild, moderate or severe). Mild is itching or hives, for example. A severe event requires emergency medical treatment and can result in death.
Time frame: Up to 7 days following skin testing
Population: Safety population, defined as subjects who received at least one concentration of omalizumab or omalizumab excipient.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects | Number of Participants by of Adverse Events Following a Skin Test Procedure | Any adverse event | 1 participants |
| Healthy Subjects | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Mild | 0 participants |
| Healthy Subjects | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Moderate | 1 participants |
| Healthy Subjects | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Severe | 0 participants |
| Allergic Asthma Participants | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Severe | 0 participants |
| Allergic Asthma Participants | Number of Participants by of Adverse Events Following a Skin Test Procedure | Any adverse event | 3 participants |
| Allergic Asthma Participants | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Moderate | 3 participants |
| Allergic Asthma Participants | Number of Participants by of Adverse Events Following a Skin Test Procedure | Severity: Mild | 0 participants |
Primary
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers)
For intradermal testing, positive control (histamine 0.1 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The intradermal test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped.
Time frame: on the day of skin test
Population: Safety population. For 1:1000 dilutions: n=27; for 1:100 dilutions: n=21; for 1:10 dilutions: n=13. The skin tests started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped (i.e., reason for different Ns per dilution.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:1000 Dilution; Excipient | 6 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:1000 Dilution; Omalizumab | 2 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:100 Dilution; Excipient | 7 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:100 Dilution; Omalizumab | 6 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:10 Dilution; Excipient | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) | 1:10 Dilution; Omalizumab | 0 participants |
Primary
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma)
For intradermal testing, positive control (histamine 0.1 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The intradermal test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped.
Time frame: on the day of skin test
Population: Safety population. For 1:100,000 dilutions: n=30; for 1:10,000 dilutions: n=29. The skin tests started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped (i.e., reason for different Ns per dilution.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) | 1:100,000 Dilution; Excipient | 1 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) | 1:100,000 Dilution; Omalizumab | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) | 1:10,000 Dilution; Excipient | 4 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) | 1:10,000 Dilution; Omalizumab | 7 participants |
Primary
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test)
For skin prick, positive control (histamine 6 mg/mL) and negative control (saline) were used. Positive skin reaction was defined as a ≥ 3-mm wheal and/or \> 10-mm erythema from negative control. The skin prick test started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped.
Time frame: on the day of skin test
Population: Safety population, defined as subjects who received at least one concentration of omalizumab or omalizumab excipient. For healthy volunteer cohort, undiluted: n=29. The skin tests started with the lowest concentration. If a positive skin reaction was observed, escalation to the next dilution was stopped (i.e., reason for different Ns per dilution.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:1000 Dilution; Excipient | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:1000 Dilution; Omalizumab | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:100 Dilution; Excipient | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:100 Dilution; Omalizumab | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:10 Dilution; Excipient | 1 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:10 Dilution; Omalizumab | 0 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | Undiluted; Excipient | 2 participants |
| Healthy Subjects | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | Undiluted; Omalizumab | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | Undiluted; Omalizumab | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:1000 Dilution; Excipient | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:10 Dilution; Excipient | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:1000 Dilution; Omalizumab | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | Undiluted; Excipient | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:100 Dilution; Excipient | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:10 Dilution; Omalizumab | 0 participants |
| Allergic Asthma Participants | Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) | 1:100 Dilution; Omalizumab | 0 participants |