Strict avoidance of peanut is essential, as even trace amounts of peanut can cause a severe allergic reactions.
Peanut allergy is one of the most common food allergies, and can cause severe, potentially fatal, allergic reactions, including anaphylaxis.
According to recent studies, food allergies, mainly peanut, are responsible for 150 to 200 deaths every year in the United States and more than 125,000 emergency room visits.
While anaphylactic shock is the most severe allergic reaction to peanuts, many patients also suffer from a poor quality of life. Peanut allergies have lifelong effects and are often associated with psychological traumas, including fear of eating, antisocial behavior and anxiety.
Allergy to peanuts appears to be on the rise and its prevalence has increased in the past 10 years. According to an article published in The Journal of Allergy and Clinical Immunology, a recent survey in the United States indicated that approximately 1% of the U.S. population, or more than three million people, are allergic to peanuts and/or nuts.
Two recent studies conducted in the United States and the United Kingdom show that peanut allergy has doubled in five years in children below age five.
A study funded by Food Allergy Research and Education, Inc., or FARE, indicates that the number of children in the United States with peanut allergy more than tripled between 1997 and 2008. Although some patients outgrow their peanut allergies, research indicates that only about 20% of individuals with peanut allergy outgrow it during a lifetime.
Development program for Viaskin® Peanut
In July 2010, we initiated the first clinical trial of Viaskin® Peanut in the United States
A Phase Ib trial to evaluate the safety and tolerability of repeated epicutaneous administration of Viaskin® Peanut in patients allergic to peanuts.
In the trial, which was conducted at five leading centers in the United States, 100 subjects (initially adults, followed by adolescents and then children) allergic to peanuts, including 70 with a non-severe allergy and 30 with a severe allergy, were randomized and treated for two weeks with 20 µg to 500 µg of Viaskin® Peanut or with placebo. The primary endpoint of this clinical trial was safety, with the primary safety parameters of adverse events, physical examinations, vital signs, lab values, allergic reactions, any skin reactions, local or distant, echo-cardiogram, and Peak Expiratory Flow and spirometry (FEV1). Secondary endpoints included the proportion of subjects that experience systemic reactions such as urticaria, asthma and acute dyspnea, change in blood pressure, and digestive symptoms (vomiting, diarrhea) associated with Viaskin® Peanut treatment versus placebo, the proportion of subjects requiring treatment for systemic reactions related to Viaskin® Peanut treatment or placebo, and overall adherence to the clinical trial treatment.
In the overall population, the dose of 500 µg of Viaskin® Peanut in adults and adolescents, and the dose of 250 µg of Viaskin® Peanut in children, were shown to be well-tolerated maximum doses regardless of the administration plan. Importantly, an excellent treatment compliance rate (> 96%) was observed and the intermediate results suggested satisfactory usage safety of Viaskin® Peanut in patients allergic to peanuts. The interim report was communicated to the FDA on December 15, 2011, and DBV Technologies released the complete results of this clinical trial at the EAACI Congress in June 2012.
VIPES (Viaskin® Peanut’s Efficacy and Safety)
In August 2012, DBV initiated VIPES, a double-blind, placebo-controlled, multi-center Phase IIb clinical trial of Viaskin® Peanut.
DBV Technologies initiated VIPES in 221 peanut allergic subjects with a well-documented medical history of systemic reactions after ingestion of peanut. Subjects completed their last food challenge visits after twelve months of treatment and we expect to announce topline results in the fourth quarter of 2014.
The VIPES trial was a multi-center clinical trial conducted at 22 sites in North America and Europe. In the trial, 221 peanut-allergic subjects were randomized into four treatment arms (55 subjects per treatment group) to evaluate three doses of Viaskin® Peanut, specifically 50 µg, 100 µg and 250 µg peanut protein, compared to placebo. Each patient underwent two double-blind, placebo-controlled food challenges, or DBPCFCs: one at initial screening and one at 12 months after initiation of treatment. The challenge was halted once the subject exhibited an objective symptom, thus establishing a subject’s peanut tolerance level. Patients in VIPES received a daily application of the Viaskin® Peanut patch over a 12-month treatment period. Each patch was applied for 24 hours, either on the upper arm for adults (age 18-55) and adolescents (age 12-17) or on the back of children (age 6-11). The primary efficacy endpoint is the percentage of treatment responders for each active treatment compared to placebo. A treatment responder is defined as a subject with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut proteins based on the results of the double-blind, placebo-controlled peanut challenge after 12 months of treatment or a subject with a ≥ 10-fold increase of the eliciting dose at 12 months, compared to the initial eliciting dose.
The principal coordinating investigator for VIPES in North America is Dr. Hugh Sampson, M.D., Chief of the Division of Allergy & Immunology in the Department of Pediatrics, Director of the Jaffe Food Allergy Institute, and Dean of Translational Biomedical Science at The Mount Sinai Medical Center in New York, United States. Dr. Sampson is also a member of the Scientific Advisory Board as well as principal investigator of the National Institutes of Health-sponsored Consortium of Food Allergy Research clinical trial with Viaskin® Peanut (CoFAR6).
The principal coordinating investigator for VIPES in Europe is Christophe Dupont, M.D., Ph.D., Head of the Pediatric-Gastroenterology Ambulatory Department at the Necker Hospital (AP-HP). He is a member of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and of the Committee of Nutrition of the French Pediatric Society. Dr. Dupont is also the Chairman of the Scientific Advisory Board.
OLFUS-VIPES (Open-Label Follow-Up Study)
In September 2013, we initiated an open-label follow-up Phase IIb clinical trial called VIPES OLFUS to assess the long-term efficacy and safety of Viaskin® Peanut in subjects with peanut allergy.
OLFUS enrolled 171 subjects who had previously received either placebo or one of three 12-month dose regimens administered during VIPES. During the first year of OLFUS, patients were to receive a daily application of Viaskin Peanut 50 µg or Viaskin Peanut 100 µg or Viaskin Peanut 250 µg for 12 months. According to a study protocol change implemented in March 2014, all patients were switched to receive Viaskin Peanut 250 μg during OLFUS. Baseline response levels in OLFUS were based on the results of the last double-blind, placebo controlled food challenge (DBPCFC) in VIPES, and adjusted by the number of patients enrolling in OLFUS. As in VIPES, a responder in the OLFUS trial was defined as a subject who could reach a peanut protein eliciting dose equal to or greater than 1,000 mg peanut protein during the 12-month DBPCFC or a subject with a ≥10-fold increase of the eliciting dose compared to the initial eliciting dose after 12 months of treatment. Patients enrolled in OLFUS who received placebo in VIPES were analyzed separately from subjects who initially received Viaskin Peanut.
During the first 12 months of OLFUS, no drug-related epinephrine use or serious adverse events (SAEs) due to Viaskin Peanut were reported. The study’s median compliance rate, which was maintained at 96%, was also consistent with previously reported results. A preliminary analysis of the OLFUS data showed that 12 additional months of therapy with Viaskin Peanut 250 μg increased the number of patients benefiting from treatment to 70% in OLFUS from 50% in VIPES, with 80% of children (ages 6-11 at entry in VIPES) responding to therapy after 24 months. Patients who received placebo for one year in VIPES and received Viaskin Peanut for 12 months in OLFUS showed a 50% response rate, which was consistent with findings from VIPES.
PEPITES (Peanut EPIT® Efficacy and Safety Study)
PEPITES (Peanut EPIT® Efficacy and Safety Study) is a randomized, double-blind, placebo-controlled pivotal Phase III trial designed to assess the efficacy and safety of Viaskin Peanut 250 μg in approximately 330 pediatric patients in around 30 centers in North America (United States and Canada), Australia and Europe.
During the study, patients will be assessed using a double-blind, placebo controlled food challenge (DBPCFC). Patients will be randomized 2:1 to receive either Viaskin Peanut 250 μg or placebo for 12 months. The combined primary endpoint is based on a responder analysis after 12 months of treatment with Viaskin Peanut 250 µg. For patients with a baseline peanut protein eliciting dose (ED) equal to or less than 10 mg, a responder is defined as a patient with a peanut protein ED equal to or greater than 300 mg of peanut protein after 12 months of treatment. For subjects with a baseline ED greater than 10 mg, a responder will be defined as a patient with a peanut protein eliciting dose equal to or greater than 1,000 mg of peanut protein after 12 months of treatment.
- DBV Technologies Announces Initiation of Phase III Study of Viaskin® Peanut for the Treatment of Peanut Allergic Children
- Efficacy and Safety of Viaskin Peanut in peanut-allergic children (PEPITES) - EU Clinical Trial Register
REALISE (REAL LIfe Use and Safety of EPIT)
REALISE is a multicenter, randomized, double-blind, placebo-controlled Phase III study designed to assess the use of Viaskin Peanut 250 μg in routine medical practice and generate safety data after six months of blinded treatment in patients four to 11 years of age. At the six-month time point, patients in both the placebo and active arms will be able to opt into an open-label portion of the study, which will continue monitoring patients for a total of 36 months of active treatment. Exploratory criteria will also include scores from subjects’ Food Allergy Quality of Life Questionnaire (FAQLQ) and the Food Allergy Independent Measure (FAIM), as well as the evolution of peanut-specific serological markers over time. The study is expected to be conducted in approximately 30 to 40 centers in North America.
No oral food challenges are required in REALISE. Patients in the study will be selected based on a well-documented medical history of IgE-mediated reactions to peanut, including children with a history of severe anaphylaxis, as well as analyses of peanut-specific immunological markers. During the first six months of trial, patients will be randomized 3:1 active versus placebo. Key assessments of safety parameters will include treatment-emergent adverse events observed in both the placebo and active treatment groups after the initial 6 months, which will continue to be monitored during the open-label portion of the study. DBV intends to enroll approximately 335 subjects in REALISE.
Academic development program for Viaskin® Peanut
The ARACHILD trial is a pilot trial conducted in France by the AP-HP
ARACHILD is a DBPCFC trial to investigate the efficacy and safety of Viaskin® Peanut in peanut allergic patients recruited from six centers.
In the trial, 54 patients (35 children (age 5 to 11) and 19 adolescents (age 12 to 18)), were randomized into two treatment arms to evaluate a single dose of Viaskin® Peanut, specifically 100 µg of peanut protein, compared to placebo. Patients in the placebo arm were crossed over at six months to Viaskin® Peanut without unblinding the trial. Each patient underwent DBPCFCs at months 6, 12 and 18 after initiation of treatment. After the initial double-blind six-month treatment period, all patients went through an open-label period of 30 months. Success in this trial was defined as at least a 10-fold increase in initial reactive dose or cumulative reactive dose, or CRD > 1000 mg of peanut protein (about 4 peanuts).
In June 2013, AP-HP reported the results from the initial six-month double-blind placebo-controlled phase of the trial and for the first 12 months of the open-label follow-up phase. In the active group (28 subjects), 6-, 12- and 18-month data showed 7.4%, 20% and 40% of subjects, respectively, consuming at least 10 times more peanut protein than tolerated at the beginning of the trial (versus 7.7% in the placebo arm before the crossover to Viaskin® Peanut at month six, then 13% and 19% respectively after the crossover). Net trends of a specific sub-analysis of 19 adolescents (age 12 to 17) showed that despite a positive serological response of IgE, no adolescents qualified as responders at 6, 12 and 18 months. In an analysis of 35 children (age 5 to 11), a positive serological response of IgE, but also an immunological response is characteristic of an acquisition of tolerance leading to, a continuous and progressive number of responders was observed. For the children subgroup, 6-, 12- and 18- month data showed 12.5%, 33.3% and 66.7% of subjects, respectively, consuming at least 10 times more peanut protein than at the beginning of the trial (versus 10.5% in the placebo arm before the crossover to Viaskin® Peanut at month six, then 16.7% and 23.5%, respectively, after the crossover).
Additional analyses of these data also suggest a linear relationship between body surface and response rate as well as onset of response. This analysis supports the belief that the 100 mcg dose in Viaskin® Peanut used in Arachild was potentially too low to generate a significant clinical outcome in patients with a higher body surface. In addition, these data also suggest that levels of the antibody IGg4 are potentially a good predictor of future patient response.
Consortium for Food Allergy Research 6
In October 2013, the Consortium for Food Allergy Research, or CoFAR, launched a multi-center, randomized, double-blind, placebo-controlled trial to evaluate Viaskin® Peanut in children and adults allergic to peanuts.
This trial is sponsored and funded by The National Institute of Allergy and Infectious Diseases, or NIAID, an institute of the United States National Institutes of Health and coordinated by Professor Hugh Sampson in New York. The trial is being conducted in five hospitals in the United States and includes 75 patients, both adults and children. The recruitment of CoFAR6 ended in July 2014. Subjects will be randomized to two doses of Viaskin® Peanut (100 µg and 250 µg) or matched placebo and will undergo a peanut protein oral food challenge at week 52. Expected to last four years, this trial will enable analysis of the effects of peanut desensitization with Viaskin® Peanut over an initial period of 12 months.