A DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED TRIALTO STUDY THE VIASKIN MILK EFFICACY AND SAFETY FOR TREATING IgE-MEDIATED COW[Single Quote]S MILK ALLERGY IN CHILDREN (MILES STUDY)
- Children’s Medical Center (Dallas, Plano, Southlake)
John Bird, M.D.
up to 194 subjects (18 in part a and 176 in part B) will be randomized to treatment in this study. The duration of the study will be approximately 40 months. 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 2-17 years of age with ige-mediated cow's milk allergy (CMa). Viaskin Milk is a patch containing an extract of cow's milk prote4ins. The study will be conducted at approximately 10-14 sites tin the united States and Canada, with selected investigators and staff experienced in the diagnosis and management of CMa and anaphylaxis, and who are capable of performing a double blind, placebo- controlled food challenge (DBPCFC) in children 2-11 years old and adolescents 12-17 years old. eligible subjects with confirmed ige-mediated CMa will perform a first 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 [Less Than] 300mg (approximately 9.4 ml of cow's milk) will be randomized in the study. The study will be divided into 2 consecutive parts (Part a and Part B) for randomization of the subjects to treatment. Part a will evaluate the safety of 3 escalating doses of Viaskin Milk (150ug, 300ug, 500ug of cow's milk proteins) versus placebo in successive cohorts of subjects before proceeding to Part B. in each cohort, evaluation of safety will be based on safety data collected and analyzed from subjects treated for 3 weeks. it is to be noted that after these first 3 weeks of treatment, Part a subjects will not discontinue treatment but instead will continue treatment up to Month 12, at which time subjects will undergo a second DBPCFC. Part B is designed to evaluate the efficacy and safety of up to 3 selected safe doses (as determined from part a) of Viaskin Milk versus placebo. Subjects will be randomized to receive a 12 month treatment (blinded treatment period), at which time a second DBPCFC will be performed. The efficacy of Viaskin milk will be assessed based on data pooled from subjects in both Part a and Part B, treated up to Month 12.
after the Month 12 DBPCFC, all subjects from Part a and Part B will continue treatment for another 12 months in and open label manner with Viaskin Milk, at the highest dose, 500ug, determined to be safe based on safety data from Part a subjects. Then, a third DBPCFC will be performed at Month 24. The final end of Study (eoS) visit will be performed 2 weeks later. During the study, all subjects will be instructed to remain on a cow's milk free diet with no consumption of dairy products or baked milk products. Viaskin milk patches contain a dry deposit of cow's milk proteins (150ug, 300ug, and 500ug). The placebo treatment will consist of a Viaskin patch with a similar formulation devoid of cow's milk proteins. once the patch is applied to the skin, the hypoallergenic adhesive film Tegaderm or any other alternative adhesive dressing authorized by the sponsor must be used each day to cover the Viaskin patch to prevent it from coming off the skin or moving around. The patches will be applied on the inter-scapular area on the back of children and on the inner side of the arms for adolescents. Repeated daily application of the Viaskin patch will be made from Day 1 (visit 4) for all subjects with a progressive increase of the daily duration of application as follows: 6 hours of daily application during the first week, 12 hours of daily application during the second week, and fro and entire 24 hour daily application from the third week onwards. The patch will be changed every day for the duration for the study.
1. Signed Consent From (ICF) by parents(s)/guardians9s) of subjects and informed assent form (IAF) for subjects >/= 7 years, or as per local or country specific guidelines or regulations.
2. Male or female subjects 2-17 years old at Visit 1
3. Documented medical history or physician-confirmed diagnosis or IgE-mediated CMA with systemic symptoms related ot ingestion of milk or dairy products.
4. Subjects currently following a strict cow's milk-free diet, with no consumption of dairy or baked milk products.
5. Cow[Single Quote]s milk-specific IgE level at screening =+ /- 10 kU/L
6. Positive Skin Prick Test (SPT) to cow[Single Quote]s milk with a largest wheal diameter >/= 6mm.
7. Positive DBPCFC at screening with an eliciting dose = 300mg cow[Single Quote]s milk proteins (approximately =9.4ml of cow[Single Quote]s milk
8. 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.
9. Ability to perform spirometry procedures in accordance with the American Thoracic Society Guidelines (2005) for subjects >/=6years old. Subjects,6 years of age should be able to perform peak expiratory flow (PEF) measurements. Subjects <8 years of age who have documented inability to adequately perform spirometry can perform the PEF evaluation instead. Subjects <5 years of age who have documented inability to perform he PEF evaluation 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
10. Subjects and or parents/guardians willing to comply with all study requirements during the participation in the study.