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.
