Cow’s milk protein allergy, or CMPA, is the first allergy that appears during early childhood.
CMPA is often missed in the primary care setting and can be a significant cause of infant distress when left undiagnosed.
Symptoms can include gastrointestinal problems including vomiting and diarrhea, skin rash, angioedema or rapid swelling of the skin, and anaphylaxis. The only option available for CMPA management is the avoidance of cow’s milk, which can lead to issues of dietary imbalance, failure to thrive and poor quality of life.
CMPA is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. In approximately 80% of CMPA cases, the allergy to cow’s milk disappears after age 16. However, according to an expert panel convened by the AAAAI, approximately 35% of children with severe CMPA subsequently develop other food allergies or allergic respiratory diseases, such as asthma.
Development program for Viaskin® Milk
In the second half of 2014, we have initiated MILES trial
MILES trial is a multi-center, double-blind, placebo-controlled, randomized Phase I/II trial to study the safety and efficacy of Viaskin® Milk in pediatric patient populations (age 2 to 17) with IgE-mediated CMPA.
This trial is conducted in select U.S. and Canadian clinical centers, including sites belonging to the CoFAR. Up to 150 subjects (18 subjects in Part A and 132 subjects in Part B) will be randomized for treatment at approximately 10 to 14 sites. Eligible subjects with confirmed IgE-mediated CMPA will perform a first food challenge at screening with escalating doses of cow’s milk proteins. Subjects who show the appearance of objective signs or symptoms to an eliciting dose of cow’s milk proteins ≤300 mg (approximately 9.4 mL of cow’s milk) will be randomized in the trial.
Part A of MILES, which is equivalent to Phase I, will evaluate the safety of repeated daily applications of three escalating dose-levels of Viaskin® Milk (150 µg, 300 µg and 500 µg cow’s milk protein) versus placebo during three weeks. Part B, which is equivalent to Phase II, is designed to evaluate the safety and efficacy of up to two selected doses of Viaskin® Milk (as determined from Part A), after a review of the safety data. After month 12, all subjects from Parts A and B will continue treatment for another 12 months in an open-label manner with Viaskin® Milk, at the highest dose determined to be safe based on safety data from Part A. The primary efficacy endpoint will be the percentage of subjects who are treatment responders after 12 months, defined as subjects who meet at least one of the following criteria: a ≥10-fold increase in the cumulative reactive dose, or CRD, of cow’s milk proteins at the month 12 food challenge as compared to baseline value and reaching at least 144 mg of cow’s milk proteins (approximately 4.5 mL of milk); or a CRD of cow’s milk proteins ≥1444 mg (approximately 45 mL of milk) at the month 12 food challenge. Secondary efficacy endpoints include, among other things, the percentage of subjects who are treatment responders at month 24, the mean and median CRD of cow’s milk proteins at months 12 and 24 and change from baseline, the change in the severity of symptoms elicited during the food challenge from baseline to months 12 and 24, and the change form baseline in quality of life assessments at months 12 and 24.
- Efficacy and Safety of Viaskin Milk in Children With IgE-Mediated Cow's Milk Allergy (MILES) - clinicaltrials.gov
- DBV Technologies Announces Completion of Part A of the MILES Study Evaluating the Safety of Viaskin® Milk in Pediatric Cow’s Milk Allergy
- DBV Technologies Announces First Patient Enrolled in Phase II Study of Viaskin Milk
Academic development program for Viaskin® Milk
A pilot clinical trial of Viaskin® Milk with the AP-HP
We conducted a double-blind, placebo-controlled pilot clinical trial of Viaskin® Milk with the AP-HP in 2005 in subjects with CMPA.
In this clinical trial, children (age 3 months to 15 years) with high levels of specific IgE were unable to consume more than 10 mL of cow’s milk.
In 2010, the final results of this trial were published in The Journal of Allergy and Clinical Immunology. In the trial, at the end of a three-month treatment, the mean cumulative tolerated dose increment was 12-fold in the active group versus 8% in the placebo group.
At the start of the clinical trial, out of the 19 patients included, some patients could not tolerate the equivalent of one drop of milk without having severe reactions. However, after three or six months of treatment, almost half of the Viaskin® Milk treatment group was able to ingest milk in large quantities. In contrast, no patients treated during the first three months with a placebo (patch without active substance) showed meaningful improvement. These same non-responder patients were then treated with Viaskin® Milk and after three or six months of treatment, 80% of them experienced an improvement in their tolerance of milk. There were no serious or unexpected adverse events in the trial nor premature withdrawal from the clinical trial. Although larger studies are needed to confirm the statistical efficacy, the results of the pilot clinical trial provide proof-of-concept for specific immunotherapy via the epicutaneous route for this indication.
In addition, with assistance from us, The Children’s Hospital of Philadelphia, or CHOP, intends to file an IND for a trial called SMILEE in the first half of 2015, a double-blind, placebo-controlled, randomized trial to study efficacy and safety of the Viaskin® Milk for treating milk-induced eosinophilic esophagitis in children, the SMILEE trial will be conducted as follows, subject to the applicable institutional review board, or IRB, and FDA approval. Twenty subjects aged from 4 to 17 years will be randomized into either Viaskin® Milk or placebo arms. Treatment will start at randomization, during which subjects will maintain a milk-free diet. After nine months of treatment, subjects will be re-exposed to milk for up to two months, at which point biopsies will be performed to evaluate primary endpoints.
Although we are providing assistance in the form of funding and trial supplies, this trial will be conducted by CHOP and supervised by its staff member Jonathan Spergel, MD, PhD.