Trial Outcomes & Findings for OIT and Xolair® (Omalizumab) in Cow's Milk Allergy (NCT NCT01157117)

Last Updated: 2020-08-14

Results Overview

Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of milk protein during a double-blind placebo-controlled oral food challenge were then given an open feeding of milk and those who successfully consumed the open feeding were counted as successes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

Month 32 which is 8 weeks following the discontinuation of milk OIT for both groups and 4 months after discontinuation of omalizumab for the omalizumab group

Results posted on

2020-08-14

Participant Flow

Recruitment took place at three university-based medical centers in the United States (Mount Sinai, Johns Hopkins University, Stanford University) beginning in October 2010. Accrual of randomized participants was completed in April 2012 and of untreated controls was completed in August 2012.

Participant milestones

Participant milestones
Measure	Omalizumab/Milk OIT Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Overall Study STARTED	28	29	20
Overall Study Began Omalizumab or Placebo Dosing	27	28	0
Overall Study Began Milk OIT Dosing at Month 4	27	28	0
Overall Study Reached Milk OIT Maintenance Dosing	26	26	0
Overall Study Unblinded at Month 16	26	26	0
Overall Study Completed Month 28 Desensitization OFC	26	24	0
Overall Study Discontinued Milk OIT at Month 30	24	20	0
Overall Study Completed Month 32 Tolerance OFC	24	20	0
Overall Study Completed Final Month 38 Study Visit	19	18	3
Overall Study COMPLETED	19	18	5
Overall Study NOT COMPLETED	9	11	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Omalizumab/Milk OIT Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Overall Study Dosing Symptoms	0	4	0
Overall Study Withdrawal by Subject	4	1	1
Overall Study Lack of Efficacy	1	1	0
Overall Study Lost to Follow-up	0	0	1
Overall Study Unknown (Pending Final Form Submission)	4	5	13

Baseline Characteristics

OIT and Xolair® (Omalizumab) in Cow's Milk Allergy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omalizumab/Milk OIT n=28 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=29 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=20 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.	Total n=77 Participants Total of all reporting groups
Age, Categorical <=18 years	26 Participants n=93 Participants	27 Participants n=4 Participants	20 Participants n=27 Participants	73 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	9 Participants n=4 Participants	5 Participants n=27 Participants	22 Participants n=483 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	20 Participants n=4 Participants	15 Participants n=27 Participants	55 Participants n=483 Participants
Race/Ethnicity, Customized Hispanic or Latino origin	0 participants n=93 Participants	2 participants n=4 Participants	0 participants n=27 Participants	2 participants n=483 Participants
Race/Ethnicity, Customized Non-Hispanic or non-Latino origin	28 participants n=93 Participants	27 participants n=4 Participants	20 participants n=27 Participants	75 participants n=483 Participants
Race/Ethnicity, Customized Asian	4 participants n=93 Participants	3 participants n=4 Participants	2 participants n=27 Participants	9 participants n=483 Participants
Race/Ethnicity, Customized Black/African American	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Race/Ethnicity, Customized White	23 participants n=93 Participants	26 participants n=4 Participants	18 participants n=27 Participants	67 participants n=483 Participants
Region of Enrollment United States	28 participants n=93 Participants	29 participants n=4 Participants	20 participants n=27 Participants	77 participants n=483 Participants
Age	12.6 years STANDARD_DEVIATION 4.1 • n=93 Participants	11.5 years STANDARD_DEVIATION 5.6 • n=4 Participants	11.3 years STANDARD_DEVIATION 2.9 • n=27 Participants	11.8 years STANDARD_DEVIATION 4.5 • n=483 Participants
Atopic Dermatitis Total Score	0.3 Scores on a scale STANDARD_DEVIATION 0.9 • n=93 Participants	0.5 Scores on a scale STANDARD_DEVIATION 1.5 • n=4 Participants	1.0 Scores on a scale STANDARD_DEVIATION 2.3 • n=27 Participants	0.5 Scores on a scale STANDARD_DEVIATION 1.5 • n=483 Participants
Total IgE	683.1 kU/L STANDARD_DEVIATION 658.9 • n=93 Participants	686.6 kU/L STANDARD_DEVIATION 565.7 • n=4 Participants	878.8 kU/L STANDARD_DEVIATION 824.3 • n=27 Participants	735.2 kU/L STANDARD_DEVIATION 670.3 • n=483 Participants
Milk IgE	52.2 kUA/L STANDARD_DEVIATION 47.4 • n=93 Participants	57.9 kUA/L STANDARD_DEVIATION 55.5 • n=4 Participants	72.4 kUA/L STANDARD_DEVIATION 63.9 • n=27 Participants	59.6 kUA/L STANDARD_DEVIATION 54.9 • n=483 Participants
Milk Skin Prick Test Score	8.9 mm STANDARD_DEVIATION 3.3 • n=93 Participants	9.0 mm STANDARD_DEVIATION 3.2 • n=4 Participants	NA mm STANDARD_DEVIATION NA • n=27 Participants	8.9 mm STANDARD_DEVIATION 3.2 • n=483 Participants
Age at Initial Milk Allergic Reaction	0.9 years STANDARD_DEVIATION 1.8 • n=93 Participants	0.5 years STANDARD_DEVIATION 0.5 • n=4 Participants	0.9 years STANDARD_DEVIATION 0.8 • n=27 Participants	0.7 years STANDARD_DEVIATION 1.1 • n=483 Participants

PRIMARY outcome

Timeframe: Month 32 which is 8 weeks following the discontinuation of milk OIT for both groups and 4 months after discontinuation of omalizumab for the omalizumab group

Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=28 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=29 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk	46.4 Percent of participants	34.5 Percent of participants	—

SECONDARY outcome

Timeframe: Baseline to completion of Escalation Phase at 22 to 40 weeks

Population: Participants who received any milk OIT dosing during the Escalation Phase.

Any reaction to daily milk OIT dosing recorded by the participant during the Escalation Phase.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=27 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=28 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Incidence of Dosing Reactions to Milk OIT During the Escalation Phase	81.5 percentage of participants	96.4 percentage of participants	—

SECONDARY outcome

Timeframe: After completion of Escalation Phase at 22 to 40 weeks, the Maintenance Phase lasted up to Month 30

Population: Participants who received milk OIT dosing during the Maintenance Phase.

Any reaction to daily milk OIT dosing recorded by the participant during the Maintenance Phase.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=26 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=26 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Incidence of Dosing Reactions to Milk OIT During the Maintenance Phase	46.2 percentage of participants	96.2 percentage of participants	—

SECONDARY outcome

Timeframe: Through completion of milk OIT dosing (at Month 28 if failed desensitization OFC, at Month 30 if passed desensitization OFC)

Population: Participants who received milk OIT dosing.

Participants who had a change in mental status or hypotension as a milk OIT dosing symptom were counted as having a severe hypersensitivity reaction.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=27 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=28 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Incidence of Severe Hypersensitivity Reactions to Milk OIT	0 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to completion of Escalation Phase at 22 to 40 weeks

Population: Participants who received any milk OIT dosing

Maximum tolerated dose of milk OIT is the highest dose of milk powder the participant was able to consume for at least 14 consecutive days.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=27 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=28 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Maximum Tolerated Dose of Milk Oral Immunotherapy (OIT)	9941.7 mg milk powder Standard Deviation 2692.9	9174.0 mg milk powder Standard Deviation 3344.6	—

SECONDARY outcome

Timeframe: Month 28

Population: Participants who received any study treatment

Desensitization Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of milk protein during a double-blind placebo-controlled oral food challenge were counted as successes.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=27 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=28 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Percentage of Participants in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Desensitization to Milk	88.9 percentage of participants	71.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to completion of Escalation Phase at 22 to 40 weeks

Population: Time to maximum tolerated dose could not be calculated because the maximum dose for the protocol was changed part way through the study after some subjects had already reached the maximum dose.

Time to reach the maximum tolerated dose (MTD) of milk oral immunotherapy (OIT); MTD is the highest dose of milk powder the participant was able to consume for at least 14 consecutive days.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 32

Population: All randomized participants who had not withdrawn from the study and came to the clinic for their Month 32 visit were assessed.

A milk endpoint titration is a prick skin test using 5 serial 10-fold dilutions of milk which include 1:20 wt/vol, 1:200 wt/vol, 1:2,000 wt/vol, 1:20,000 wt/vol and 1:200,000 wt/vol. The score for each of these dilutions is calculated by subtracting the diameter of the saline control wheal from the diameter of the milk wheal (in millimeters). The area under the curve is calculated by adding together the scores from all 5 milk dilutions creating a composite score.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=25 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=22 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change From Baseline to Month 32 in Area Under the Curve for Milk Endpoint Titration Prick Skin Test	-12.5 units on a scale Interval -32.0 to 3.0	-15.3 units on a scale Interval -45.0 to -1.5	—

SECONDARY outcome

Timeframe: Month 32

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 32 visit, and for whom valid results were reported.

The level of milk IgE in plasma as well as the IgE levels of 2 milk proteins, casein and beta-lactoglobulin, were measured. The value for each participant was subtracted from the value for that participant at baseline. Month 32 was the last visit on treatment.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=25 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=22 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=6 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change From Baseline to Month 32 in Antigen-specific Immunoglobulin E (IgE) Change in Beta-lactoglobulin IgE	-1.7 kUA/L Interval -72.5 to 59.1	-2.9 kUA/L Interval -129.5 to 41.6	7.2 kUA/L Interval -33.7 to 41.7
Change From Baseline to Month 32 in Antigen-specific Immunoglobulin E (IgE) Change in Milk IgE	-9.8 kUA/L Interval -134.2 to 50.5	-16.9 kUA/L Interval -121.7 to 200.0	0.8 kUA/L Interval -78.4 to 103.4
Change From Baseline to Month 32 in Antigen-specific Immunoglobulin E (IgE) Change in Casein IgE	-6.2 kUA/L Interval -194.1 to 596.0	-27.7 kUA/L Interval -170.6 to 69.0	3.5 kUA/L Interval -76.1 to 177.2

SECONDARY outcome

Timeframe: Month 32

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 32 visit, and for whom valid results were reported.

Casein and beta-lactoglobulin milk proteins IgG4 levels were measured in plasma. The value for each participant was subtracted from the value for that participant at baseline. Month 32 was the last visit on treatment.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=25 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=22 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=6 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change From Baseline to Month 32 in Antigen-specific Immunoglobulin G4 (IgG4) Change in Casein IgG4	17.3 mgA/L Interval 0.2 to 57.2	13.5 mgA/L Interval -0.2 to 47.4	0.1 mgA/L Interval -0.3 to 60.4
Change From Baseline to Month 32 in Antigen-specific Immunoglobulin G4 (IgG4) Change in Beta-lactoglobulin IgG4	24.9 mgA/L Interval -0.1 to 58.7	20.8 mgA/L Interval -0.1 to 62.3	-0.02 mgA/L Interval -1.3 to 52.5

SECONDARY outcome

Timeframe: Month 38

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 38 visit, and for whom valid results were reported.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=18 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=18 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=5 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change From Baseline to Month 38 in Antigen-specific Immunoglobulin E (IgE) Change in Milk IgE	-25.1 kUA/L Interval -135.6 to 37.0	-15.8 kUA/L Interval -147.5 to 18.1	-1.0 kUA/L Interval -8.3 to 95.4
Change From Baseline to Month 38 in Antigen-specific Immunoglobulin E (IgE) Change in Casein IgE	-14.9 kUA/L Interval -194.8 to 58.0	-34.8 kUA/L Interval -189.5 to 7.4	1.6 kUA/L Interval -0.6 to 71.2
Change From Baseline to Month 38 in Antigen-specific Immunoglobulin E (IgE) Change in Beta-lactoglobulin IgE	-2.7 kUA/L Interval -73.8 to 68.1	-2.6 kUA/L Interval -139.2 to 91.1	1.9 kUA/L Interval -13.1 to 28.0

SECONDARY outcome

Timeframe: Month 38

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 38 visit, and for whom valid results were reported.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=18 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=18 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=5 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change From Baseline to Month 38 in Antigen-specific Immunoglobulin G4 (IgG4) Change in Beta-lactoglobulin IgG4	23.8 mgA/L Interval 0.1 to 121.5	25.6 mgA/L Interval -2.6 to 125.0	-0.02 mgA/L Interval -0.7 to 0.3
Change From Baseline to Month 38 in Antigen-specific Immunoglobulin G4 (IgG4) Change in Casein IgG4	44.9 mgA/L Interval 0.6 to 100.3	21.0 mgA/L Interval -1.5 to 56.5	0.4 mgA/L Interval -0.6 to 16.6

SECONDARY outcome

Timeframe: Month 32

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 32 visit, and for whom valid results were reported.

Basophil cells isolated from blood using flow cytometry were stimulated with 5 different levels of milk and the percent of basophil cells that were CD63 positive was measured. The value for each participant obtained at Month 32 was subtracted from the value for that participant at baseline. The 5 different levels of milk stimulant were: 10 µg/mL, 1 µg/mL , 0.1 µg/mL , 0.01 µg/mL , and 0.001 µg/mL. Month 32 was the last visit on treatment.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=21 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=19 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=5 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk Change in %CD63+ for 0.001 µg/mL stimulant	-1.3 percentage of CD63+ basophils Interval -41.5 to 19.1	-1.2 percentage of CD63+ basophils Interval -44.0 to 85.5	1.9 percentage of CD63+ basophils Interval -1.7 to 7.5
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk Change in %CD63+ for 10 µg/mL stimulant	11.1 percentage of CD63+ basophils Interval -19.8 to 81.2	8.7 percentage of CD63+ basophils Interval -61.4 to 76.0	13.0 percentage of CD63+ basophils Interval 10.3 to 25.5
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk Change in %CD63+ for 1 µg/mL stimulant	7.5 percentage of CD63+ basophils Interval -37.3 to 74.2	0.6 percentage of CD63+ basophils Interval -56.6 to 85.2	6.9 percentage of CD63+ basophils Interval -2.6 to 40.9
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk Change in %CD63+ for 0.1 µg/mL stimulant	-11.8 percentage of CD63+ basophils Interval -57.3 to 34.2	-5.5 percentage of CD63+ basophils Interval -53.2 to 79.1	15.9 percentage of CD63+ basophils Interval -7.3 to 45.9
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk Change in %CD63+ for 0.01 µg/mL stimulant	-6.5 percentage of CD63+ basophils Interval -47.5 to 23.2	-3.8 percentage of CD63+ basophils Interval -59.2 to 87.6	26.2 percentage of CD63+ basophils Interval -4.7 to 35.5

SECONDARY outcome

Timeframe: Month 38

Population: All randomized participants and untreated controls who had not withdrawn from the study, came to the clinic for their Month 38 visit, and for whom valid results were reported.

Basophil cells isolated from blood using flow cytometry were stimulated with 5 different levels of milk and the percent of basophil cells that were CD63 positive was measured. The value for each participant obtained at Month 38 was subtracted from the value for that participant at baseline. The 5 different levels of milk stimulant were: 10 µg/mL, 1 µg/mL , 0.1 µg/mL , 0.01 µg/mL , and 0.001 µg/mL. Month 38 was 6 months after treatment ended at Month 32.

Outcome measures

Outcome measures
Measure	Omalizumab/Milk OIT n=19 Participants Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=18 Participants Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Untreated Control n=5 Participants Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk Change in %CD63+ for 10 µg/mL stimulant	-9.2 percentage of CD63+ basophils Interval -59.3 to 56.6	-11.7 percentage of CD63+ basophils Interval -72.9 to 46.1	26.7 percentage of CD63+ basophils Interval 14.0 to 53.0
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk Change in %CD63+ for 1 µg/mL stimulant	-8.2 percentage of CD63+ basophils Interval -53.1 to 17.2	-9.5 percentage of CD63+ basophils Interval -57.5 to 57.7	29.5 percentage of CD63+ basophils Interval -0.2 to 37.8
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk Change in %CD63+ for 0.1 µg/mL stimulant	-18.6 percentage of CD63+ basophils Interval -59.4 to 1.8	-21.6 percentage of CD63+ basophils Interval -63.0 to 0.0	28.6 percentage of CD63+ basophils Interval 17.2 to 42.2
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk Change in %CD63+ for 0.01 µg/mL stimulant	-10.2 percentage of CD63+ basophils Interval -61.9 to 0.5	-7.8 percentage of CD63+ basophils Interval -64.5 to 8.5	8.4 percentage of CD63+ basophils Interval -10.1 to 36.2
Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk Change in %CD63+ for 0.001 µg/mL stimulant	-5.2 percentage of CD63+ basophils Interval -59.3 to 0.8	-4.0 percentage of CD63+ basophils Interval -43.7 to 3.6	1.6 percentage of CD63+ basophils Interval -2.2 to 39.6

Adverse Events

Omalizumab/Milk OIT

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo for Omalizumab/Milk OIT

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Untreated Control

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Omalizumab/Milk OIT n=28 participants at risk Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.	Placebo for Omalizumab/Milk OIT n=29 participants at risk Placebo for omalizumab: Placebo for omalizumab is injected subcutaneously every 2-4 weeks for 16 months at a volume designed to match that of the omalizumab treatment group (determined by the participant's IgE level and weight).	Untreated Control n=20 participants at risk Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Infections and infestations Abscess	3.6% 1/28 • Number of events 1 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.	0.00% 0/29 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.	0.00% 0/20 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/28 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.	0.00% 0/29 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.	5.0% 1/20 • Number of events 1 • Adverse Events were reported through the end of the study. Other \[Not Including Serious\] Adverse Events in the Untreated Control Arm were reported only in the 72 hours after any study-specific blood draws.

Other adverse events

Additional Information

Dr. Hugh A. Sampson

Ichan School of Medicine at Mount Sinai

Phone: 212-659-9426

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place