Allergies Food Milk
Conditions
Keywords
Food allergy, Milk allergy, Oral Immunotherapy
Brief summary
This is a phase 2, multicenter, randomized, double-blind, parallel group, 2 arm study in approximately 40 subjects aged 4 to 50 years, inclusive, who are allergic to cow's milk. The primary objective is to assess whether dupilumab as an adjunct to milk oral immunotherapy (OIT) compared to placebo improves the safety of milk OIT and rates of desensitization, defined as an increase in the proportion of subjects who pass a double-blind placebo-controlled food challenge (DBPCFC) to at least 2040 mg cumulative milk protein at week 18.
Interventions
DRUGDupilumab
Dupilumab injected every 2 weeks for 18 weeks
OTHERPlacebo
Placebo injected every 2 weeks for 18 weeks
Sponsors
Robert Levin Charitable Fund
Regeneron Pharmaceuticals
Andrew J Long, PharmD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
dupilumab or placebo arm
Eligibility
Sex/Gender
ALL
Age
4 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Age 4 to 50 years (inclusive) * Clinical history of allergy to cow's milk or milk-containing foods * Serum IgE to milk of \>4 kUA/L within the last 12 months and/or a SPT to milk ≥6 mm compared to a negative control * Experience clinical reaction at or before 444 mg cumulative protein dose of cow's milk protein on Screening DBPCFC * No clinical reaction observed during the placebo (oat) Screening DBPCFC * Subjects with other known food allergies must agree to eliminate these other food items from their diet so as not to confound the safety and efficacy data from the study * Use of effective birth control by female participants of childbearing potential
Exclusion criteria
* Any previous exposure to dupilumab * Known hypersensitivity to dupilumab or any of its excipients * Known hypersensitivity to epinephrine or any of its excipients * Allergy to oat (placebo in DBPCFC) * History of severe anaphylaxis to cow's milk, defined as neurological compromise or requiring intubation * Recent history of frequent severe, life-threatening episodes of anaphylaxis or anaphylactic shock as defined as 3 or more episodes of anaphylaxis within the past year * Inability to tolerate biological (antibody) therapies * Body weight \<5 kg at the time of screening * History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (e.g., difficulty swallowing, food getting stuck), or recurrent gastrointestinal symptoms of undiagnosed etiology * History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension * History of a mast cell disorder * Established diagnosis of a primary immunodeficiency disorder * Severe asthma or mild or moderate asthma if uncontrolled or difficult to control * Current participation or within the last 4 months in any other interventional study * Use of medication such as beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18 | Week 18 | DBPCFC double-blind, placebo-controlled food challenge; OIT oral immunotherapy; withdrawals are imputed as failures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 18 DBPCFC | Week 18 | DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures |
| Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 24 DBPCFC | week 24 | DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures |
| Proportion of Participants Who Tolerate at Least 2040 mg Cumulative Milk Protein at Week 24 DBPCFC | Week 24 | DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures |
| Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 18 DBPCFC | Week 18 | DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures |
| Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline and week 18 | Baseline values reflect the log10 of cumulative tolerated dose (CTD) of milk protein. The change metric reflects the order of magnitude of paired differences in CTD between baseline and week 18. |
| Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline and week 24 | Baseline values reflect the log10 of cumulative tolerated dose (CTD) of milk protein. The change metric reflects the order of magnitude of paired differences in CTD between baseline and week 24. |
| Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 24 DBPCFC | Week 24 | DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures |
Countries
United States
Participant flow
Pre-assignment details
Of 33 enrolled, 8 participants failed at screening and 2 withdrew from the study prior to randomization, for a total of 10 participants consented but not randomized
Participants by arm
| Arm | Count |
|---|---|
| Active Dupilumab and Milk OIT Dupilumab every two to four weeks for 4 weeks, followed by dupilumab every two to four weeks plus milk OIT for 12 weeks, then milk OIT alone for 8 weeks | 11 |
| Placebo for Dupilumab and Milk OIT Placebo for dupilumab every two to four weeks for 4 weeks, followed by placebo for dupilumab every two to four weeks plus milk OIT for 12 weeks, then milk OIT alone for 8 weeks | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Active Dupilumab and Milk OIT | Total | Placebo for Dupilumab and Milk OIT |
|---|---|---|---|
| Age, Customized 11 - 17 years | 4 Participants | 7 Participants | 3 Participants |
| Age, Customized 18+ years | 3 Participants | 6 Participants | 3 Participants |
| Age, Customized 4 - 10 years | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 20 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| History of Atopy Allergic Rhinitis | 6 Participants | 12 Participants | 6 Participants |
| History of Atopy Asthma | 7 Participants | 15 Participants | 8 Participants |
| History of Atopy Atopic Disease | 9 Participants | 16 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 10 / 11 | 11 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18
DBPCFC double-blind, placebo-controlled food challenge; OIT oral immunotherapy; withdrawals are imputed as failures
Time frame: Week 18
Population: Intention to treat population: all randomized patients, analyzed in the treatment group they were assigned to, regardless of whether they actually received the treatment, dropped out, or deviated from the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18 | 8 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18 | 5 Participants |
Secondary
Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups
Baseline values reflect the log10 of cumulative tolerated dose (CTD) of milk protein. The change metric reflects the order of magnitude of paired differences in CTD between baseline and week 18.
Time frame: Baseline and week 18
Population: Participants with week 18 data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Change at week 18 | 1.574 log10 mg cumulative tolerated protein | Standard Deviation 0.88 |
| Active Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline | 1.632 log10 mg cumulative tolerated protein | Standard Deviation 0.888 |
| Placebo for Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline | 1.899 log10 mg cumulative tolerated protein | Standard Deviation 0.6 |
| Placebo for Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Change at week 18 | 1.127 log10 mg cumulative tolerated protein | Standard Deviation 0.618 |
Secondary
Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups
Baseline values reflect the log10 of cumulative tolerated dose (CTD) of milk protein. The change metric reflects the order of magnitude of paired differences in CTD between baseline and week 24.
Time frame: Baseline and week 24
Population: Participants with week 24 data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline | 1.632 log10 mg cumulative tolerated protein | Standard Deviation 0.888 |
| Active Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Change at week 24 | 1.559 log10 mg cumulative tolerated protein | Standard Deviation 1.153 |
| Placebo for Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Baseline | 1.898 log10 mg cumulative tolerated protein | Standard Deviation 0.691 |
| Placebo for Dupilumab and Milk OIT | Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups | Change at week 24 | 1.366 log10 mg cumulative tolerated protein | Standard Deviation 0.49 |
Secondary
Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 18 DBPCFC
DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures
Time frame: Week 18
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 18 DBPCFC | 5 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 18 DBPCFC | 3 Participants |
Secondary
Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 24 DBPCFC
DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures
Time frame: Week 24
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 24 DBPCFC | 5 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 24 DBPCFC | 3 Participants |
Secondary
Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 18 DBPCFC
DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures
Time frame: Week 18
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 18 DBPCFC | 9 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 18 DBPCFC | 6 Participants |
Secondary
Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 24 DBPCFC
DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures
Time frame: week 24
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 24 DBPCFC | 8 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 24 DBPCFC | 5 Participants |
Secondary
Proportion of Participants Who Tolerate at Least 2040 mg Cumulative Milk Protein at Week 24 DBPCFC
DBPCFC double-blind, placebo-controlled food challenge; withdrawals are imputed as failures
Time frame: Week 24
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 2040 mg Cumulative Milk Protein at Week 24 DBPCFC | 7 Participants |
| Placebo for Dupilumab and Milk OIT | Proportion of Participants Who Tolerate at Least 2040 mg Cumulative Milk Protein at Week 24 DBPCFC | 5 Participants |