Trial Outcomes & Findings for Baked Milk Oral Immunotherapy for Cow's Milk Allergy (NCT NCT03462030)
NCT ID: NCT03462030
Last Updated: 2025-02-04
Results Overview
Adverse events will be recorded per CTCAE version 4.0. Events per dose on baked milk oral immunotherapy will be compared to adverse events per dose on placebo. Data will be collected over the first year of treatment. Analysis of cumulative adverse reactions per dose of oral immunotherapy or placebo will be performed at the end of year 1.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
1 year
Results posted on
2025-02-04
Participant Flow
Participants were recruited from the Johns Hopkins (JH) Pediatric Allergy Clinic, Baltimore, MD from March 2018 to October 2019.
41 subjects were consented and screened. Eleven (27%) did not have dose-limiting symptoms in their screening food challenge to 444mg of baked milk protein and were therefore ineligible for the study. 30 subjects were randomized 1:1.
Participant milestones
| Measure |
Baked Milk Immunotherapy
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
End of Build-up
|
14
|
14
|
|
Overall Study
Month 12 Food Challenge
|
14
|
14
|
|
Overall Study
COMPLETED
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Baked Milk Immunotherapy
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Baked Milk Oral Immunotherapy for Cow's Milk Allergy
Baseline characteristics by cohort
| Measure |
Baked Milk Immunotherapy
n=15 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
13 years
n=5 Participants
|
7 years
n=7 Participants
|
11 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Cow's Milk IgE
|
114 kU/L
n=5 Participants
|
87 kU/L
n=7 Participants
|
88 kU/L
n=5 Participants
|
|
Age at Milk Allergy Diagnosis
|
8 months
n=5 Participants
|
9 months
n=7 Participants
|
8.5 months
n=5 Participants
|
|
Participants with Prior Baked Milk Exposure
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Participants with a History of milk reaction
Unheated Milk Only
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Participants with a History of milk reaction
Baked Milk Only
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Participants with a History of milk reaction
Both Unheated and Baked Milk
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Current Atopic History
Asthma
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Current Atopic History
Atopic dermatitis
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Current Atopic History
Allergic rhinitis
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Current Atopic History
Non-milk food allergies
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Alpha lactalbumin IgE (kU/L)
|
20.4 kU/L
n=5 Participants
|
19.7 kU/L
n=7 Participants
|
20 kU/L
n=5 Participants
|
|
Beta lactoglobulin igE (kU/L)
|
28.2 kU/L
n=5 Participants
|
18.8 kU/L
n=7 Participants
|
24.5 kU/L
n=5 Participants
|
|
Casein IgE (kU/L)
|
75.8 kU/L
n=5 Participants
|
52.8 kU/L
n=7 Participants
|
64.8 kU/L
n=5 Participants
|
|
Milk IgG4 (mg/L)
|
8.6 mg/L
n=5 Participants
|
9.4 mg/L
n=7 Participants
|
9.2 mg/L
n=5 Participants
|
|
Milk skin prick test
|
14 mm
n=5 Participants
|
10 mm
n=7 Participants
|
13 mm
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearAdverse events will be recorded per CTCAE version 4.0. Events per dose on baked milk oral immunotherapy will be compared to adverse events per dose on placebo. Data will be collected over the first year of treatment. Analysis of cumulative adverse reactions per dose of oral immunotherapy or placebo will be performed at the end of year 1.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=15 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
|
15 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: 1 yearThe investigators will perform baked milk challenges to 4044 mg of baked milk protein and calculate the proportion of subjects who tolerate 4 grams of baked milk protein after one year of baked milk oral immunotherapy. This measure reports the number of participants that were able to tolerate 4 grams of baked milk protein.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=15 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Proportion of Subjects Who Are Able to Tolerate 4 Grams of Baked Milk Protein After One Year of Treatment
|
11 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe investigators will perform unheated milk challenges to up to 8000 mg of unheated milk protein and calculate the proportion of subjects who tolerate 2 grams of unheated milk protein after 2 years of treatment. This measure reports the number of participants that were able to tolerate 2 grams of unheated milk protein.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=15 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Number of Subjects Who Are Able to Tolerate 2 Grams of Unheated Milk Protein After 2 Years of Treatment
|
8 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline, 1 year and 2 yearsChange in maximum tolerated dose (milligrams) of baked milk from baseline to end of year 1 and end of year 2.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=15 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Change in Maximum Tolerated Dose of Baked Milk
Change from baseline to 1 year
|
3900 miligrams
Interval 2256.0 to 4025.0
|
0 miligrams
Interval 0.0 to 757.0
|
|
Change in Maximum Tolerated Dose of Baked Milk
Change from baseline to 2 years
|
3900 miligrams
Interval 2371.0 to 4025.0
|
3900 miligrams
Interval 2031.0 to 3900.0
|
SECONDARY outcome
Timeframe: Baseline and up to year 2Population: For change from baseline to year 1, 1 participant dropped out in each group so blood/results only available for 14 participants in each group. 4 participants dropped out in year 2 so blood/results was available for 12 in each group for change from baseline to year 2.
Change in milk-specific immunoglobulin E (IgE) level measured in kU/L.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=14 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=14 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Change in Milk-specific IgE Level
change from baseline to 1 year
|
-21.35 KU/L
Interval -40.08 to 6.67
|
-14.75 KU/L
Interval -41.73 to 12.42
|
|
Change in Milk-specific IgE Level
change from baseline to 2 years
|
-77.45 KU/L
Interval -138.95 to -15.69
|
-46.65 KU/L
Interval -109.47 to -14.6
|
SECONDARY outcome
Timeframe: Baseline and up to year 2Population: For change from baseline to year 1, 1 participant dropped out in each group so blood/results only available for 14 participants in each group. 4 participants dropped out in year 2 so blood/results was available for 12 in each group for change from baseline to year 2.
Change in milk-specific immunoglobulin G4 (IgG4) level measured in mg/L.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=14 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=14 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Change in Milk-specific IgG4 Level
change from baseline to 1 year
|
8.88 mg/L
Interval 4.58 to 85.34
|
3.79 mg/L
Interval 2.69 to 4.26
|
|
Change in Milk-specific IgG4 Level
Change from baseline to 2 years
|
5.5 mg/L
Interval 1.79 to 8.99
|
3.55 mg/L
Interval 2.45 to 11.26
|
SECONDARY outcome
Timeframe: Baseline and up to year 2Population: For change from baseline to year 1, 1 participant dropped out in each group so SPT results only were available for 14 participants in each group. 4 participants dropped out in year 2 so SPT results was available for 12 in each group for change from baseline to year 2.
Change in milk skin prick test responses measured as a change in wheal size in millimeters.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=14 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=14 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Change in Milk Skin Prick Test Responses
Change from baseline to year 1
|
-2.5 millimeters
Interval -10.0 to 3.0
|
3.5 millimeters
Interval -2.16 to 14.99
|
|
Change in Milk Skin Prick Test Responses
Change from baseline to 2 years
|
-4 millimeters
Interval -7.79 to 1.79
|
1.5 millimeters
Interval -6.47 to 10.0
|
SECONDARY outcome
Timeframe: Baseline and up to year 2Population: For change from baseline to year 1, 1 participant dropped out in each group so questionnaire results only were available for 14 participants in each group. 4 participants dropped out in year 2 so questionnaire results was available for 12 in each group for change from baseline to year 2.
The food allergy questionnaire has an overall score range of 0-6 with 6 indicating the worst quality of life.
Outcome measures
| Measure |
Baked Milk Immunotherapy
n=14 Participants
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=14 Participants
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Change in Quality of Life as Assessed by the Food Allergy Questionnaire
change from baseline to 1 year
|
0.04 score on a scale
Standard Deviation 0.79
|
0.37 score on a scale
Standard Deviation 1.08
|
|
Change in Quality of Life as Assessed by the Food Allergy Questionnaire
change from baseline to 2 years
|
-0.07 score on a scale
Standard Deviation 0.94
|
-0.3 score on a scale
Standard Deviation 1.16
|
Adverse Events
Baked Milk Immunotherapy
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Baked Milk Immunotherapy
n=15 participants at risk
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 participants at risk
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hospitalization - asthma
|
0.00%
0/15 • 1 year
Adverse events were recorded by body system affected.
|
13.3%
2/15 • Number of events 2 • 1 year
Adverse events were recorded by body system affected.
|
|
Psychiatric disorders
Hospitalization - mental health
|
0.00%
0/15 • 1 year
Adverse events were recorded by body system affected.
|
6.7%
1/15 • Number of events 1 • 1 year
Adverse events were recorded by body system affected.
|
Other adverse events
| Measure |
Baked Milk Immunotherapy
n=15 participants at risk
Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Baked non-fat cow's milk powder: Oral immunotherapy with increasing quantities of baked milk.
|
Placebo
n=15 participants at risk
Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period.
Placebo: Tapioca Powder: Placebo control.
|
|---|---|---|
|
General disorders
Oropharyngeal symptoms
|
93.3%
14/15 • 1 year
Adverse events were recorded by body system affected.
|
53.3%
8/15 • 1 year
Adverse events were recorded by body system affected.
|
|
Skin and subcutaneous tissue disorders
Cutaneous symptoms
|
93.3%
14/15 • 1 year
Adverse events were recorded by body system affected.
|
80.0%
12/15 • 1 year
Adverse events were recorded by body system affected.
|
|
Gastrointestinal disorders
Gastrointestinal symptoms
|
100.0%
15/15 • 1 year
Adverse events were recorded by body system affected.
|
93.3%
14/15 • 1 year
Adverse events were recorded by body system affected.
|
|
Respiratory, thoracic and mediastinal disorders
Lower respiratory tract symptoms
|
80.0%
12/15 • 1 year
Adverse events were recorded by body system affected.
|
93.3%
14/15 • 1 year
Adverse events were recorded by body system affected.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place