Trial Outcomes & Findings for The Safety and Utility of Skin Testing With XOLAIR® (Omalizumab) and Placebo Omalizumab (Formulation Excipients) (NCT NCT00777764)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

Up to 7 days following skin testing

Results posted on

2017-06-14

Participant Flow

Participant milestones

Participant milestones
Measure	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).	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.
Overall Study STARTED	30	30
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Safety and Utility of Skin Testing With XOLAIR® (Omalizumab) and Placebo Omalizumab (Formulation Excipients)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Subjects n=30 Participants 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).	Allergic Asthma Participants n=30 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.	Total n=60 Participants Total of all reporting groups
Age, Continuous	33.8 years STANDARD_DEVIATION 13.10 • n=5 Participants	32.0 years STANDARD_DEVIATION 10.88 • n=7 Participants	32.9 years STANDARD_DEVIATION 11.97 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	17 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	13 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 days following skin testing

Population: Safety population, defined as subjects who received at least one concentration of omalizumab or omalizumab excipient.

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.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=30 Participants 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).	Allergic Asthma Participants n=30 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.
Number of Participants by of Adverse Events Following a Skin Test Procedure Any adverse event	1 participants	3 participants
Number of Participants by of Adverse Events Following a Skin Test Procedure Severity: Mild	0 participants	0 participants
Number of Participants by of Adverse Events Following a Skin Test Procedure Severity: Moderate	1 participants	3 participants
Number of Participants by of Adverse Events Following a Skin Test Procedure Severity: Severe	0 participants	0 participants

PRIMARY outcome

Timeframe: 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.)

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.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=30 Participants 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).	Allergic Asthma Participants n=30 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.
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:1000 Dilution; Excipient	0 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:1000 Dilution; Omalizumab	0 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:100 Dilution; Excipient	0 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:100 Dilution; Omalizumab	0 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:10 Dilution; Excipient	1 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) 1:10 Dilution; Omalizumab	0 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) Undiluted; Excipient	2 participants	0 participants
Number of Participants Who Experienced a Positive Skin Reaction (Skin Prick Test) Undiluted; Omalizumab	0 participants	0 participants

PRIMARY outcome

Timeframe: 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.)

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.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=27 Participants 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).	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.
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:1000 Dilution; Excipient	6 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:1000 Dilution; Omalizumab	2 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:100 Dilution; Excipient	7 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:100 Dilution; Omalizumab	6 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:10 Dilution; Excipient	0 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Healthy Volunteers) 1:10 Dilution; Omalizumab	0 participants	—

PRIMARY outcome

Timeframe: 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.)

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.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=30 Participants 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).	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.
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) 1:100,000 Dilution; Excipient	1 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) 1:100,000 Dilution; Omalizumab	0 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) 1:10,000 Dilution; Excipient	4 participants	—
Number of Participants Who Experienced a Positive Skin Reaction (Intradermal Test in Patients With Allergic Asthma) 1:10,000 Dilution; Omalizumab	7 participants	—

Adverse Events

Healthy Subjects

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Allergic Asthma Participants

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Subjects n=30 participants at risk 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).	Allergic Asthma Participants n=30 participants at risk 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.
Infections and infestations Gastroenteritis	0.00% 0/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.	3.3% 1/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.
Infections and infestations Sinusitis	0.00% 0/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.	3.3% 1/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.
Nervous system disorders Headache	3.3% 1/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.	3.3% 1/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.
Nervous system disorders Syncope	3.3% 1/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.	0.00% 0/30 Safety-evaluable population. Note: The incidence of each AE is reported as the number of participants experiencing the event, not the number of occurrences for each AE. AEs are reported regardless of the investigator's assessment of relation to study drug.

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER