Food Allergy
Conditions
Keywords
Milk Allergy,, Viaskin Milk,, Specific Immunotherapy,, Epicutaneous ImmunoTherapy (EPIT), IgE-Mediated Cow's Milk Allergy
Brief summary
The objectives of this study are to evaluate the safety and efficacy of Viaskin Milk after 12 months of epicutaneous immunotherapy (EPIT) treatment, for desensitizing IgE-mediated cow's milk allergic children and to assess the long-term safety and therapeutic benefit with Viaskin Milk.
Detailed description
This is a multi-center, double-blind, placebo-controlled, randomized trial to study the safety and efficacy of Viaskin Milk applied epicutaneously every day to subjects from 2 to 17 years of age with IgE-mediated cow's milk allergy (CMA). Subjects will receive blinded treatment for 1 year at one of the 3 doses of Viaskin Milk: 150µg, 300µg, 500µg or placebo. After the first year, all subjects were to switch to the highest dose of Viaskin Milk, 500µg, and continue treatment in an open-label manner for up to a maximum of 3 additional years. Following results of the 12-month blinded period, all eligible subjects who wish to continue participation in the study will switch from Viaskin Milk 500µg to Viaskin Milk 300µg for 24 months of treatment. Eligible subjects with confirmed IgE-mediated CMA will perform a first Double-Blind Placebo-Controlled Food Challenge (DBPCFC) at screening with escalating doses of cow's milk proteins. Subjects showing a positive DBPCFC at screening, defined as the appearance of objective signs or symptoms to an eliciting dose of cow's milk proteins ≤300 mg (approximately ≤9.4mL of cow's milk) will be randomized in the study to receive a 12 month treatment (blinded treatment period), at which time a second DBPCFC will be performed to evaluate the primary efficacy endpoint of the study. Approximately 194 subjects will be randomized in this study. The total duration of participation in the study will differ for each individual subject and could be up to approximately 6 years.
Interventions
BIOLOGICALViaskin Milk 150 mcg
Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.
BIOLOGICALViaskin Milk 300 mcg
Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.
BIOLOGICALViaskin Milk 500 mcg
Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.
BIOLOGICALViaskin Placebo
Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Sponsors
DBV Technologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Eligibility criteria for study enrollment: Inclusion Criteria: * Signed Informed Consent Form (ICF) by parent(s)/guardian(s) of subjects and informed assent form (IAF) for subjects ≥7 years, or as per local or country specific guidelines or regulations. * Male or female subjects 2 to 17 years old at Visit 1. * Documented medical history or physician-confirmed diagnosis of IgE-mediated CMA with systemic symptoms related to ingestion of milk or dairy products. * Subjects currently following a strict cow's milk-free diet, with no consumption of dairy or baked milk products. * Cow's milk-specific IgE level at screening ≥10 kU/L * Positive Skin Prick Test (SPT) to cow's milk with a largest wheal diameter ≥6 mm. * Positive DBPCFC at screening with an eliciting dose ≤300 mg cow's milk proteins (approximately ≤9.4 mL of cow's milk). * Negative urine pregnancy test for female subjects of childbearing potential. Female subjects of childbearing potential must agree and commit to use effective medical methods of contraception for the entire duration of their participation in the study. Sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age. * Ability to perform spirometry procedures in accordance with the American Thoracic Society guidelines (2005) for subjects ≥6 years old. Ability to perform peak expiratory flow (PEF) measurements for subjects ≥5 years old. Subjects \<8 years of age who have documented inability to adequately perform spirometry can perform only the PEF evaluation. Subjects \<5 years of age may be enrolled if they had no clinical features of moderate or severe persistent asthma severity (as defined by the 2007 National Heart, Lung, and Blood Institute \[NHLBI\] Guidelines) within 1 year before Visit 1. * Subjects and/or parents/guardians willing to comply with all study requirements during participation in the study.
Exclusion criteria
* History of severe anaphylaxis to cow's milk resulting in hypotension, hypoxia or neurological compromise (collapse, loss of consciousness or incontinence) or requiring mechanical ventilation. * Pregnancy or lactation. * Spirometry forced expiratory volume in 1 second (FEV1) \<80% of the predicted value at Visit 1 for subjects ≥6 years and able to perform the spirometry, or PEF \<80% of predicted value at Visit 1 for subjects performing only the PEF measurements. * Any clinical features of moderate or severe persistent asthma severity (as defined by the 2007 NHLBI guidelines) and high daily doses of inhaled corticosteroids. * Known allergy to the Viaskin patch materials or excipients, or to any of the components of the food challenge formulas other than the cow's milk proteins. * Allergy or known history of reaction to Tegaderm® medical dressing with no possibility to use an alternative adhesive dressing authorized by the sponsor in replacement. * Subjects having objective symptoms to the placebo formula leading to stopping the challenge during the screening DBPCFC. * Severe reaction during the screening DBPCFC defined as need for intubation, and/or hypotension persisting after epinephrine administration, and/or the need for \>2 doses of epinephrine. * Symptomatic allergy to pollens with symptoms during the pollen season that might interfere with the symptoms observed during the DBPCFC, if the DBPCFC is performed during the pollen season. Screening of such subjects should be made out of the pollen season. * Inability to discontinue short-acting antihistamines for 3 days or long-acting antihistamines for 5 to 7 days (depending on the half-life) before the DBPCFC. * Use of systemic long-acting corticosteroids within 12 weeks before Visit 1 and/or use of systemic short-acting corticosteroids within 4 weeks before Visit 1 or use of systemic long-acting or short-acting corticosteroids during screening (unless used to treat symptoms triggered by the DBPCFC or triggered by accidental allergen consumption; in the latter case DBPCFC must then be scheduled after a minimum of 7 wash-out days). * Subjects with asthma conditions meeting 1 or several criteria below: * Uncontrolled persistent asthma (as defined by the 2007 NHLBI guidelines) or subject being treated with a combination therapy of medium or high daily dose of inhaled corticosteroid with a long acting inhaled β2-agonist. Intermittent asthmatic subjects who require intermittent use of inhaled corticosteroids for rescue are permitted. * At least 2 systemic corticosteroid courses for asthma within 1 year before Visit 1 or 1 oral corticosteroid course for asthma within 3 months before Visit 1, or during screening (unless used to treat symptoms triggered by the DBPCFC). * Prior intubation/mechanical ventilation due to asthma within 2 years before Visit 1, or during screening. * Upper respiratory infection or gastroenteritis within 7 days of DBPCFC (DBPCFC must then be rescheduled at least 7 days after resolution of these conditions). * Any history of milk immunotherapy (eg, oral immunotherapy, sublingual immunotherapy or specific oral tolerance induction). * Prior history of any other food allergen immunotherapy (eg, oral immunotherapy, sublingual immunotherapy or specific oral tolerance induction) within 5 years before Visit 1. * Subjects currently under aeroallergen immunotherapy and unwilling or unable to discontinue at the time of Visit 1. Aeroallergen Immunotherapy must be discontinued at the time of Visit 1. * Use of any anti-IgE drug (eg, omalizumab), any immunomodulatory therapy, or any biological agent therapy (eg, anti-tumor necrosis factor drugs) within 1 year before Visit 1, or during screening. * Generalized dermatologic diseases (eg, severe atopic dermatitis, uncontrolled generalized eczema, icthyosis vulgaris) with no intact zones to apply the Viaskin patch, or urticarial and mast cells disorders such as chronic idiopathic urticaria. * Subject and/or subject's parents/guardians with obvious excessive anxiety and unlikely to cope with the conditions of a food challenge. * Past or current disease, including but not limited to active eosinophilic gastrointestinal disorders, autoimmune disorders, immunodeficiency, malignancy, uncontrolled disease (hypertension, diabetes, psychiatric disorder, cardiac disease), or other disorders (eg, liver, gastrointestinal, kidney, cardiovascular, pulmonary disease or blood disorder) which in the opinion of the Investigator or the sponsor may affect the subject's participation in the study or place the subject at increased risk. * Subjects and/or parents/guardians unable to use the epinephrine auto-injector properly in spite of being adequately trained. * Contraindicated condition for the use of epinephrine. * Use of any investigational drug or device, or participation in another interventional clinical study within 3 months before Visit 1. * Subjects receiving beta-blockers or Angiotensin converting-enzyme (ACE) inhibitors. * Subjects unable to follow the protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment. | From baseline to Month 12 (double-blind period) | A treatment responder is defined as a subject who meets at least one of the following criteria: * A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; * A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | From baseline to Month 12 (double-blind period) | Change in Median CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins. |
| Change in Levels of sIgE to Cow's Milk. | From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period) | Median change from baseline value in levels of IgE specific to cow's milk proteins |
| Change in Levels of sIgG4 to Cow's Milk. | From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period) | Median change from baseline value in levels of IgG4 specific to cow's milk proteins |
| Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period) | Median change from baseline in levels of IgE specific to caseins, α-lactalbumin and β-lactoglobulin proteins |
| Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period) | Median change from baseline in levels of IgG4 specific to caseins, α-lactalbumin and β-lactoglobulin proteins |
| Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | From baseline to Month 12 (double-blind period) | Change in CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins. |
| Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | From baseline to Month 12 (double-blind period) | Summary of total objective severity score for DBPCFC. The total objective severity score is calculated as the sum of the severity grades (0-Absent, 1-Mild, 2-Moderate or 3-Severe) of the following objective symptoms: pruritus, urticaria/angioedema, rash, sneezing/itching, nasal congestion, rhinorrhea, laryngeal, wheezing, diarrhea, vomiting, cardiovascular and conjunctivitis for DBPCFC with cow's milk formula. The total objective score ranges from a minimum of 0 to a maximum of 36 (if the maximum grade 3 was reported for each of the 12 symptoms), with a higher score meaning a worse outcome. A negative score in the changes to Month 0 means improvement. |
| Change in Quality of Life (QoL) Assessments. | From baseline to Month 12 (double-blind period) | Summary of Global Score for Food Allergy Quality of Life Questionnaire Parent Child Form (FAQLQ-PF). The scores range from 1 (no problem/impairment) to 7 (maximal problem/impairment). A negative score in the changes to Month 0 means improvement. |
| Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | From baseline to Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period) | A treatment responder is defined as a subject who meets at least one of the following criteria: A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC. DBPCFC at Month 12 and Month 24 after switch to Viaskin Milk 300µg was optional and therefore outcome measure was assessed on observed data only. |
| Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Baseline, Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period) | Median CRD during Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins. |
| Treatment-Emergent Adverse Events | Whole study including double-blind and open-label periods (up to 6 years). | Overview of Treatment Emergent Adverse Events (TEAEs) and serious Treatment-Emergent Adverse Events |
| Change in Skin Prick Test (SPT) Wheal. | From baseline to Month 3, Month 6, Month 12 (double-blind period) | Median change from baseline in SPT Wheal diameter |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Viaskin Milk 150 mcg One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months.
Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins. | 49 |
| Viaskin Milk 300 mcg One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months.
Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins. | 49 |
| Viaskin Milk 500 mcg One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months.
Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins. | 47 |
| Viaskin Placebo One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months.
Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation. | 53 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 0 | 2 | 1 | 0 |
| Double-Blind Period | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Double-Blind Period | Non Compliance | 0 | 0 | 0 | 1 |
| Double-Blind Period | Sponsor or Regulatory Authorities Decision | 1 | 0 | 0 | 0 |
| Double-Blind Period | Withdrawal by Subject | 1 | 1 | 1 | 0 |
| Open-Label 300 Period | Lost to Follow-up | 1 | 0 | 1 | 0 |
| Open-Label 300 Period | Non Compliance | 0 | 2 | 1 | 0 |
| Open-Label 300 Period | Withdrawal by Subject | 10 | 13 | 13 | 15 |
| Open-Label 500 Period | Adverse Event | 1 | 0 | 2 | 1 |
| Open-Label 500 Period | Physician Decision | 0 | 0 | 0 | 1 |
| Open-Label 500 Period | Sponsor or Regulatory Authorities Decision | 0 | 0 | 1 | 0 |
| Open-Label 500 Period | Withdrawal by Subject | 5 | 2 | 9 | 8 |
Baseline characteristics
| Characteristic | Viaskin Milk 300 mcg | Total | Viaskin Milk 150 mcg | Viaskin Placebo | Viaskin Milk 500 mcg |
|---|---|---|---|---|---|
| Age, Continuous | 7.7 years STANDARD_DEVIATION 4.34 | 8.0 years STANDARD_DEVIATION 4.17 | 7.6 years STANDARD_DEVIATION 4.56 | 8.1 years STANDARD_DEVIATION 4.31 | 8.7 years STANDARD_DEVIATION 3.37 |
| Cow's milk sIgE | 67.6 kU/L | 61.9 kU/L | 58.2 kU/L | 61.1 kU/L | 64.6 kU/L |
| Cow's milk sIgG4 | 14.5 mgA/L | 14.0 mgA/L | 14.0 mgA/L | 13.5 mgA/L | 14.0 mgA/L |
| Cumulative Reactive Dose (CRD) of Cow's milk | 144 mg of cow's milk proteins | 144 mg of cow's milk proteins | 144 mg of cow's milk proteins | 144 mg of cow's milk proteins | 144 mg of cow's milk proteins |
| Race/Ethnicity, Customized Asian | 10 Participants | 32 Participants | 8 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 8 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 28 Participants | 133 Participants | 33 Participants | 41 Participants | 31 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 20 Participants | 5 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Female | 12 Participants | 74 Participants | 24 Participants | 18 Participants | 20 Participants |
| Sex: Female, Male Male | 37 Participants | 124 Participants | 25 Participants | 35 Participants | 27 Participants |
| Skin Prick Test Mean wheal diameter | 11.0 millimeters | 10.5 millimeters | 10.5 millimeters | 11.0 millimeters | 10.5 millimeters |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 49 | 0 / 47 | 0 / 53 | 0 / 185 | 0 / 140 |
| other Total, other adverse events | 49 / 49 | 48 / 49 | 47 / 47 | 53 / 53 | 181 / 185 | 131 / 140 |
| serious Total, serious adverse events | 3 / 49 | 2 / 49 | 1 / 47 | 2 / 53 | 16 / 185 | 7 / 140 |
Outcome results
Primary
Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment.
A treatment responder is defined as a subject who meets at least one of the following criteria: * A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; * A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC.
Time frame: From baseline to Month 12 (double-blind period)
Population: Overall Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Viaskin Milk 150 mcg | Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment. | 36.7 percent of participants |
| Viaskin Milk 300 mcg | Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment. | 49.0 percent of participants |
| Viaskin Milk 500 mcg | Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment. | 36.2 percent of participants |
| Viaskin Placebo | Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment. | 30.2 percent of participants |
Secondary
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin
Median change from baseline in levels of IgE specific to caseins, α-lactalbumin and β-lactoglobulin proteins
Time frame: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | -0.02 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | -1.36 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | -4.60 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | -2.09 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | -0.04 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | -5.60 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | -5.80 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | 1.15 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | -0.29 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | 0.07 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | -0.16 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | -1.21 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | -0.20 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | -0.53 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | -2.00 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.45 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | 1.40 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | -1.76 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.15 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | 0.18 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | -0.06 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | -5.80 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | -0.92 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | -0.12 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | -7.20 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.50 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | 1.15 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | -8.45 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | -12.60 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | -0.10 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | -1.78 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | -3.72 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.00 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | -1.17 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | -3.55 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | -4.02 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | -1.00 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | -0.48 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | -1.80 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | -0.60 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | -4.45 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | -2.55 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | -2.29 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | -1.11 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | -1.20 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | -0.71 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | -2.46 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | -0.41 kU/L |
Secondary
Change in Levels of sIgE to Cow's Milk.
Median change from baseline value in levels of IgE specific to cow's milk proteins
Time frame: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Cow's Milk. | Month 6 | -5.80 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Cow's Milk. | Week 3 | -2.43 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Cow's Milk. | Month 3 | -0.70 kU/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgE to Cow's Milk. | Month 12 | -5.90 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Cow's Milk. | Month 12 | -2.70 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Cow's Milk. | Month 6 | -5.00 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Cow's Milk. | Week 3 | 2.80 kU/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgE to Cow's Milk. | Month 3 | 3.20 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Cow's Milk. | Month 3 | -6.99 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Cow's Milk. | Week 3 | -2.30 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Cow's Milk. | Month 6 | -14.40 kU/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgE to Cow's Milk. | Month 12 | -20.60 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Cow's Milk. | Month 3 | -7.20 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Cow's Milk. | Week 3 | -5.40 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Cow's Milk. | Month 12 | -7.70 kU/L |
| Viaskin Placebo | Change in Levels of sIgE to Cow's Milk. | Month 6 | -5.45 kU/L |
Secondary
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin
Median change from baseline in levels of IgG4 specific to caseins, α-lactalbumin and β-lactoglobulin proteins
Time frame: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | 0.22 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | 0.47 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | 1.28 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.11 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.03 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | 0.32 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | 0.47 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | 0.39 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | 0.36 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | 0.00 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | 0.63 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | 1.09 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | 1.08 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | 1.64 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | 1.05 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.08 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | 0.67 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | 2.72 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.15 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | 0.81 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | 0.06 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | 1.04 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | 2.06 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | 0.94 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | 1.94 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.15 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | 0.78 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | 0.69 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | 0.61 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | 0.00 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | 0.65 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | 1.19 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.11 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | 0.65 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | 0.88 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | 1.55 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 3 | 0.00 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Week 3 | 0.00 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Week 3 | 0.03 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 3 | -0.01 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 12 | -0.11 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 6 | -0.01 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 12 | -0.06 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Month 6 | -0.03 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 12 | 0.00 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | α-lactalbumin - Month 6 | 0.00 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | Caseins - Month 3 | -0.06 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin | β-lactoglobulin - Week 3 | 0.00 mgA/L |
Secondary
Change in Levels of sIgG4 to Cow's Milk.
Median change from baseline value in levels of IgG4 specific to cow's milk proteins
Time frame: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Cow's Milk. | Week 3 | 0.24 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 3 | 0.90 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 6 | 0.10 mgA/L |
| Viaskin Milk 150 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 12 | 1.20 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 3 | 2.45 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 6 | 1.30 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 12 | 3.50 mgA/L |
| Viaskin Milk 300 mcg | Change in Levels of sIgG4 to Cow's Milk. | Week 3 | 0.90 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 6 | 1.40 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 3 | 2.60 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Cow's Milk. | Month 12 | 1.96 mgA/L |
| Viaskin Milk 500 mcg | Change in Levels of sIgG4 to Cow's Milk. | Week 3 | 0.80 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Cow's Milk. | Month 12 | -1.60 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Cow's Milk. | Month 3 | -0.80 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Cow's Milk. | Week 3 | -0.35 mgA/L |
| Viaskin Placebo | Change in Levels of sIgG4 to Cow's Milk. | Month 6 | -1.60 mgA/L |
Secondary
Change in Quality of Life (QoL) Assessments.
Summary of Global Score for Food Allergy Quality of Life Questionnaire Parent Child Form (FAQLQ-PF). The scores range from 1 (no problem/impairment) to 7 (maximal problem/impairment). A negative score in the changes to Month 0 means improvement.
Time frame: From baseline to Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Quality of Life (QoL) Assessments. | Month 0 | 4.6 score on a scale |
| Viaskin Milk 150 mcg | Change in Quality of Life (QoL) Assessments. | Change from Month 0 to Month 12 | -0.1 score on a scale |
| Viaskin Milk 150 mcg | Change in Quality of Life (QoL) Assessments. | Month 12 | 4.3 score on a scale |
| Viaskin Milk 300 mcg | Change in Quality of Life (QoL) Assessments. | Month 0 | 4.4 score on a scale |
| Viaskin Milk 300 mcg | Change in Quality of Life (QoL) Assessments. | Change from Month 0 to Month 12 | 0.1 score on a scale |
| Viaskin Milk 300 mcg | Change in Quality of Life (QoL) Assessments. | Month 12 | 4.5 score on a scale |
| Viaskin Milk 500 mcg | Change in Quality of Life (QoL) Assessments. | Month 0 | 4.6 score on a scale |
| Viaskin Milk 500 mcg | Change in Quality of Life (QoL) Assessments. | Month 12 | 4.3 score on a scale |
| Viaskin Milk 500 mcg | Change in Quality of Life (QoL) Assessments. | Change from Month 0 to Month 12 | 0 score on a scale |
| Viaskin Placebo | Change in Quality of Life (QoL) Assessments. | Month 0 | 4.9 score on a scale |
| Viaskin Placebo | Change in Quality of Life (QoL) Assessments. | Change from Month 0 to Month 12 | -0.4 score on a scale |
| Viaskin Placebo | Change in Quality of Life (QoL) Assessments. | Month 12 | 4.1 score on a scale |
Secondary
Change in Skin Prick Test (SPT) Wheal.
Median change from baseline in SPT Wheal diameter
Time frame: From baseline to Month 3, Month 6, Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 3 | -1 millimeters (mm) |
| Viaskin Milk 150 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 12 | 0 millimeters (mm) |
| Viaskin Milk 150 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 6 | 0 millimeters (mm) |
| Viaskin Milk 300 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 3 | -1 millimeters (mm) |
| Viaskin Milk 300 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 12 | -1 millimeters (mm) |
| Viaskin Milk 300 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 6 | -2 millimeters (mm) |
| Viaskin Milk 500 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 6 | -1 millimeters (mm) |
| Viaskin Milk 500 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 3 | -1 millimeters (mm) |
| Viaskin Milk 500 mcg | Change in Skin Prick Test (SPT) Wheal. | Month 12 | -1 millimeters (mm) |
| Viaskin Placebo | Change in Skin Prick Test (SPT) Wheal. | Month 3 | 0 millimeters (mm) |
| Viaskin Placebo | Change in Skin Prick Test (SPT) Wheal. | Month 12 | 0 millimeters (mm) |
| Viaskin Placebo | Change in Skin Prick Test (SPT) Wheal. | Month 6 | 0 millimeters (mm) |
Secondary
Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC).
Summary of total objective severity score for DBPCFC. The total objective severity score is calculated as the sum of the severity grades (0-Absent, 1-Mild, 2-Moderate or 3-Severe) of the following objective symptoms: pruritus, urticaria/angioedema, rash, sneezing/itching, nasal congestion, rhinorrhea, laryngeal, wheezing, diarrhea, vomiting, cardiovascular and conjunctivitis for DBPCFC with cow's milk formula. The total objective score ranges from a minimum of 0 to a maximum of 36 (if the maximum grade 3 was reported for each of the 12 symptoms), with a higher score meaning a worse outcome. A negative score in the changes to Month 0 means improvement.
Time frame: From baseline to Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 0 | 6 score on a scale |
| Viaskin Milk 150 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Change from Month 0 to Month 12 | -1 score on a scale |
| Viaskin Milk 150 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 12 | 5 score on a scale |
| Viaskin Milk 300 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 0 | 6 score on a scale |
| Viaskin Milk 300 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Change from Month 0 to Month 12 | 0 score on a scale |
| Viaskin Milk 300 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 12 | 6 score on a scale |
| Viaskin Milk 500 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 12 | 6 score on a scale |
| Viaskin Milk 500 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 0 | 6 score on a scale |
| Viaskin Milk 500 mcg | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Change from Month 0 to Month 12 | 0 score on a scale |
| Viaskin Placebo | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 0 | 6 score on a scale |
| Viaskin Placebo | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Change from Month 0 to Month 12 | 0 score on a scale |
| Viaskin Placebo | Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). | Month 12 | 6 score on a scale |
Secondary
Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period
Median CRD during Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.
Time frame: Baseline, Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period)
Population: All subjects from the Open-Label Set 300 (OLS-300) for whom this outcome measure was collected and analyzed. OLS-300 includes all subjects who entered the open-label treatment period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this open-label period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 0 | 144 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 150 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 24 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 150 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 12 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 300 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 0 | 144 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 300 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 24 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 300 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 12 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 500 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 12 after switch to Viaskin Milk 300µg | 1319 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 500 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 0 | 144 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 500 mcg | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 24 after switch to Viaskin Milk 300µg | 1219 milligrams (mg) of cow's milk proteins |
| Viaskin Placebo | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 0 | 144 milligrams (mg) of cow's milk proteins |
| Viaskin Placebo | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 24 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
| Viaskin Placebo | Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period | Month 12 after switch to Viaskin Milk 300µg | 1444 milligrams (mg) of cow's milk proteins |
Secondary
Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins.
Change in CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.
Time frame: From baseline to Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viaskin Milk 150 mcg | Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 745.1 milligrams (mg) of cow's milk proteins | Standard Deviation 1197.08 |
| Viaskin Milk 300 mcg | Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 1201.0 milligrams (mg) of cow's milk proteins | Standard Deviation 1675.9 |
| Viaskin Milk 500 mcg | Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 723.5 milligrams (mg) of cow's milk proteins | Standard Deviation 1218.26 |
| Viaskin Placebo | Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 555.5 milligrams (mg) of cow's milk proteins | Standard Deviation 1143.21 |
Secondary
Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins.
Change in Median CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.
Time frame: From baseline to Month 12 (double-blind period)
Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Viaskin Milk 150 mcg | Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 300 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 300 mcg | Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 400 milligrams (mg) of cow's milk proteins |
| Viaskin Milk 500 mcg | Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 93 milligrams (mg) of cow's milk proteins |
| Viaskin Placebo | Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins. | 100 milligrams (mg) of cow's milk proteins |
Secondary
Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data
A treatment responder is defined as a subject who meets at least one of the following criteria: A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC. DBPCFC at Month 12 and Month 24 after switch to Viaskin Milk 300µg was optional and therefore outcome measure was assessed on observed data only.
Time frame: From baseline to Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period)
Population: All subjects from the Open-Label Set 300 (OLS-300) for whom this outcome measure was collected and analyzed. OLS-300 includes all subjects who entered the open-label treatment period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this open-label period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 12 after switch to Viaskin Milk 300µg | 85.7 Percentage of participants |
| Viaskin Milk 150 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 24 after switch to Viaskin Milk 300µg | 80.0 Percentage of participants |
| Viaskin Milk 300 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 24 after switch to Viaskin Milk 300µg | 84.6 Percentage of participants |
| Viaskin Milk 300 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 12 after switch to Viaskin Milk 300µg | 72.7 Percentage of participants |
| Viaskin Milk 500 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 12 after switch to Viaskin Milk 300µg | 62.5 Percentage of participants |
| Viaskin Milk 500 mcg | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 24 after switch to Viaskin Milk 300µg | 50.0 Percentage of participants |
| Viaskin Placebo | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 12 after switch to Viaskin Milk 300µg | 81.8 Percentage of participants |
| Viaskin Placebo | Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data | Month 24 after switch to Viaskin Milk 300µg | 64.3 Percentage of participants |
Secondary
Treatment-Emergent Adverse Events
Overview of Treatment Emergent Adverse Events (TEAEs) and serious Treatment-Emergent Adverse Events
Time frame: Whole study including double-blind and open-label periods (up to 6 years).
Population: Safety set. It includes all subjects who applied at least one Viaskin patch.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Viaskin Milk 150 mcg | Treatment-Emergent Adverse Events | Any serious TEAE | 9 participants |
| Viaskin Milk 150 mcg | Treatment-Emergent Adverse Events | Any TEAE | 49 participants |
| Viaskin Milk 150 mcg | Treatment-Emergent Adverse Events | Any TEAE leading to death | 0 participants |
| Viaskin Milk 150 mcg | Treatment-Emergent Adverse Events | Any TEAE related to the Investigational Product | 46 participants |
| Viaskin Milk 150 mcg | Treatment-Emergent Adverse Events | Any serious TEAE related to the Investigational Product | 0 participants |
| Viaskin Milk 300 mcg | Treatment-Emergent Adverse Events | Any TEAE related to the Investigational Product | 43 participants |
| Viaskin Milk 300 mcg | Treatment-Emergent Adverse Events | Any serious TEAE related to the Investigational Product | 0 participants |
| Viaskin Milk 300 mcg | Treatment-Emergent Adverse Events | Any TEAE | 48 participants |
| Viaskin Milk 300 mcg | Treatment-Emergent Adverse Events | Any TEAE leading to death | 0 participants |
| Viaskin Milk 300 mcg | Treatment-Emergent Adverse Events | Any serious TEAE | 6 participants |
| Viaskin Milk 500 mcg | Treatment-Emergent Adverse Events | Any serious TEAE | 6 participants |
| Viaskin Milk 500 mcg | Treatment-Emergent Adverse Events | Any TEAE | 47 participants |
| Viaskin Milk 500 mcg | Treatment-Emergent Adverse Events | Any TEAE related to the Investigational Product | 39 participants |
| Viaskin Milk 500 mcg | Treatment-Emergent Adverse Events | Any serious TEAE related to the Investigational Product | 0 participants |
| Viaskin Milk 500 mcg | Treatment-Emergent Adverse Events | Any TEAE leading to death | 0 participants |
| Viaskin Placebo | Treatment-Emergent Adverse Events | Any serious TEAE related to the Investigational Product | 0 participants |
| Viaskin Placebo | Treatment-Emergent Adverse Events | Any serious TEAE | 7 participants |
| Viaskin Placebo | Treatment-Emergent Adverse Events | Any TEAE | 53 participants |
| Viaskin Placebo | Treatment-Emergent Adverse Events | Any TEAE related to the Investigational Product | 48 participants |
| Viaskin Placebo | Treatment-Emergent Adverse Events | Any TEAE leading to death | 0 participants |