Efficacy and Safety of Viaskin Peanut in Children With Immunoglobulin E (IgE)-Mediated Peanut Allergy (PEPITES)

A Double-blind, Placebo-controlled, Randomized Phase 3 Pivotal Trial to Assess the Efficacy and Safety of Peanut Epicutaneous Immunotherapy With Viaskin Peanut in Peanut-allergic Children

The PEPITES study evaluates the efficacy and safety of Viaskin Peanut 250 µg peanut protein to induce desensitization to peanut in peanut-allergic children 4 through 11 years of age after a 12-month treatment by epicutaneous immunotherapy (EPIT).

Study Overview

• Status: Completed
• Conditions: Peanut Allergy
• Intervention / Treatment: Biological: Viaskin Peanut 250mcg; Biological: Placebo

Detailed Description

This is a 12-month, Phase III, double-blind, placebo-controlled, randomized study to assess the efficacy and safety of Viaskin Peanut, dosed at 250µg peanut protein (per patch) in peanut-allergic children from 4 through 11 years of age.

The overall maximum study duration for each subject is approximately 61 weeks (6-week screening period, 12-month treatment period and 2-week follow-up period).

During the screening period, subjects will undergo a first screening visit and an entry double-blind, placebo-controlled food challenge (DBPCFC) to peanut to confirm their allergy and their entry peanut eliciting dose (ED). The starting dose of the challenge will be 1 mg peanut protein and will escalate up to a highest dose of 300mg peanut protein. Subjects who react at or below the dose of 300mg peanut protein are considered eligible.

Randomization of eligible subjects will occur in a 2:1 ratio to Viaskin Peanut dosed at 250µg peanut protein (active treatment) or placebo. Subjects will be stratified at randomization by their entry/screening DBPCFC ED in 1 of the following 2 strata and by study center:

• Stratum 1: children with a screening ED of 1mg, 3mg or 10mg;
• Stratum 2: children with a screening ED of 30mg, 100mg or 300mg.

Subjects will apply a Viaskin patch containing either peanut protein or placebo daily for a period of 12 months. At Month 12, a post-treatment DBPCFC to peanut will be performed, with a starting dose of 1 mg peanut protein with escalation up to a highest dose of 2,000 mg peanut protein. This evaluation will help determine the primary efficacy endpoint of this pivotal study.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Allergy Medical
  • Perth, Australia
    • Princess Margaret Hospital for Children
  • Sydney, Australia
    • Children's Hospital Westmead
• Canada
  • Quebec, Canada, QC G1V4M6
    • Centre de Recherche Appliquée en Allergie de Québec (CRAAQ)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5H 3V4
      • British Columbia Children's Hospital
  • Ontario
    • Mississauga, Ontario, Canada, L5A 3V4
      • Cheema Research Inc.
    • Ottawa, Ontario, Canada, K1Y 4G2
      • Ottawa Allergy Asthma Research Institute
    • Toronto, Ontario, Canada, M4V 1R2
      • Gordon Sussman Clinical Research Inc.
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C4
      • CHUM & CHU Sainte-Justine
• Germany
  • Berlin, Germany, D-13353
    • Charité Universitätsmedizin Berlin
  • Bonn, Germany, D-53115
    • St.-Marien-Hospital
  • Erlangen, Germany
    • Universitätsklinikum Erlangen
• Ireland
  • Cork, Ireland
    • Clinical Investigations Unit
  • Dublin, Ireland
    • Our Lady's Children's Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • San Diego, California, United States, 92123
      • University of California, Rady Children's Hospital
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens' Hospital
  • New York
    • New York, New York, United States, 10029
      • Jaffe Food Allergy Institute
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina - Chapell Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98115
      • ASTHMA, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Male or female children aged 4 through 11 years;
2. Physician-diagnosis of peanut allergy or children with a well documented medical history of IgE-mediated symptoms after ingestion of peanut and currently following a strict peanut-free diet, but without a physician diagnosis;
3. Peanut-specific IgE level (ImmunoCAP system) >0.7 kU/L;

4. Positive peanut skin prick test (SPT) with a largest wheal diameter:

   • ≥6 mm for children 4 through 5 years of age at Visit 1,
   • ≥8 mm for children 6 years and above at Visit 1;
5. Positive DBPCFC at ≤300 mg peanut protein.

Main Exclusion Criteria:

1. History of severe anaphylaxis to peanut with any of the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence);
2. Generalized dermatologic disease
3. Diagnosis of mast cell disorders, including mastocytosis or uricaria pigmentosa as well as hereditary or idiopathic angioedema;

4. Diagnosis of asthma that fulfills any of the following criteria:

   • Uncontrolled persistent asthma as defined by National Asthma Education and Prevention Program Asthma guidelines 2007 or by Global Initiative for Asthma guidelines 2015,
   • Asthma treated with either a high daily high dose of inhaled corticosteroid or with a combination therapy of a medium or high daily dose of inhaled corticosteroid with a long acting inhaled β2 agonist or with a combination therapy of a high daily dose of inhaled corticosteroid with a long acting inhaled β2 agonist. Asthmatic subjects treated with a medium daily dose of inhaled corticosteroids are eligible. Intermittent asthmatic subjects who require intermittent use of inhaled corticosteroids for rescue are also eligible,
   • Two or more systemic corticosteroid courses for asthma in the past year or 1 oral corticosteroid course for asthma within 3 months prior to Visit 1, or during screening period,
   • Prior intubation/mechanical ventilation for asthma within 1 year prior to Visit 1, or during screening;
5. Receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy;
6. Received anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy within 1 year prior to Visit 1, during screening period or during study participation;
7. Use of systemic long-acting corticosteroids within 12 weeks prior to Visit 1 and/or use of systemic short-acting corticosteroids within 4 weeks prior to Visit 1 or during screening;
8. Prior or concomitant history of any immunotherapy to any food;
9. Receiving or planning to receive any aeroallergen immunotherapy during their participation in the study. Aeroallergen immunotherapy must be discontinued at the time of Visit 1;
10. Any disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Viaskin Peanut 250mcg; One Viaskin epicutaneous delivery system (patch) containing 250 µg of peanut protein applied on the skin for 24 hours (±4 hours of allowance) daily for a period of 12 months.	Biological: Viaskin Peanut 250mcg; Peanut extract cutaneous patch; Other Names: DBV712
Placebo Comparator: Placebo; One Viaskin epicutaneous delivery system (patch) containing placebo applied on the skin for 24 hours (±4 hours of allowance) daily for a period of 12 months.	Biological: Placebo; Cutaneous patch containing an inactive deposit manufactured to mimic peanut extract

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Percentages of Treatment Responders at Month 12; Analyzed in the Overall Population	The Double-Blind Placebo-Controlled Food Challenges (DBPCFCs) to determine Eliciting Dose (ED) were performed at screening and Month 12, with each challenge occurring over 2 days. The participant was gradually fed increasing amounts of standardized blinded oral formulas containing either peanut protein (during 1 of the 2 days of the challenge), or without any peanut protein (during the other day of the challenge). A participant was defined as a treatment responder if: ED was ≥300 mg peanut protein at Month 12 DBPCFC (for screening ED subgroup 1), or; ED was ≥1,000 mg peanut protein at Month 12 DBPCFC (for screening ED subgroup 2). Participants with missing treatment response at Month 12 were imputed as non-responders. The percentage of treatment responders at Month 12 is presented. Analysis of the difference in response rates between treatment groups is presented in the subsequent statistical analysis table. Analysis was performed in the overall population.	At Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Reactive Dose (CRD) of Peanut Protein at Baseline and Month 12	The CRD was calculated as the sum of all doses given (including any repeated and partial doses). The median CRD of peanut protein at baseline and Month 12 is presented. Analysis was performed using the modified baseline observation carried forward method to impute missing data at Month 12.	Baseline and Month 12
Difference in Percentages of Treatment Responders at Month 12; Analyzed in Each Screening Eliciting Dose (ED) Subgroup	The Double-Blind Placebo-Controlled Food Challenges (DBPCFCs) to determine Eliciting Dose (ED) were performed at screening and Month 12, with each challenge occurring over 2 days. The participant was gradually fed increasing amounts of blinded oral formulas containing either peanut protein (during 1 of the 2 days of the challenge), or without any peanut protein (during the other day of the challenge). A participant was defined as a treatment responder if: ED was ≥300 mg peanut protein at Month 12 DBPCFC (for screening ED subgroup 1), or; ED was ≥1,000 mg peanut protein at Month 12 DBPCFC (for screening ED subgroup 2). Participants with missing treatment response at Month 12 were imputed as non-responders. The percentage of treatment responders at Month 12 is presented below. Analysis of the difference in response rates between treatment groups is presented in the subsequent statistical analysis table. Analysis was performed for each separate screening ED subgroup.	At Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Change From Baseline in Peanut-specific Immunoglobulin E (IgE) Over Time	Venous blood samples were drawn to assess peanut-specific IgE levels at baseline and Months 3, 6 and 12. The median relative changes from baseline in IgE levels for each timepoint are presented. Relative change from baseline=100×(value at the visit-value at baseline)/value at baseline.	Baseline and Months 3, 6 and 12
Relative Changes From Baseline in Peanut-specific Immunoglobulin G4 Subtype (IgG4) Over Time	Venous blood samples were drawn to assess peanut-specific IgG4 levels at baseline and Months 3, 6 and 12. The median relative changes from baseline in IgG4 levels for each timepoint are presented. Relative change from baseline=100×(value at the visit-value at baseline)/value at baseline.	Baseline and Months 3, 6 and 12

Collaborators and Investigators

• Sponsor: DBV Technologies
• Investigators: Principal Investigator: David M Fleischer, MD, Children's Hospital Colorado

Publications and helpful links

General Publications

• Fleischer DM, Greenhawt M, Sussman G, Begin P, Nowak-Wegrzyn A, Petroni D, Beyer K, Brown-Whitehorn T, Hebert J, Hourihane JO, Campbell DE, Leonard S, Chinthrajah RS, Pongracic JA, Jones SM, Lange L, Chong H, Green TD, Wood R, Cheema A, Prescott SL, Smith P, Yang W, Chan ES, Byrne A, Assa'ad A, Bird JA, Kim EH, Schneider L, Davis CM, Lanser BJ, Lambert R, Shreffler W. Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial. JAMA. 2019 Mar 12;321(10):946-955. doi: 10.1001/jama.2019.1113.
• Greenhawt M, Kim EH, Campbell DE, Green TD, Lambert R, Fleischer DM. Improvements in eliciting dose across baseline sensitivities following 12 months of epicutaneous immunotherapy (EPIT) in peanut-allergic children aged 4 to 11 years. J Allergy Clin Immunol Pract. 2020 Oct;8(9):3219-3221. doi: 10.1016/j.jaip.2020.05.030. Epub 2020 Jun 2. No abstract available.
• Remington BC, Campbell DE, Green TD, Fleischer DM, Koppelman SJ. Post hoc analysis of epicutaneous immunotherapy for peanut allergy phase 3 results: Relevance for exposure through restaurant meals. Ann Allergy Asthma Immunol. 2021 Feb;126(2):208-209. doi: 10.1016/j.anai.2020.11.015. Epub 2020 Nov 28. No abstract available.
• Remington BC, Krone T, Kim EH, Bird JA, Green TD, Lack G, Fleischer DM, Koppelman SJ. Estimated risk reduction to packaged food reactions by epicutaneous immunotherapy (EPIT) for peanut allergy. Ann Allergy Asthma Immunol. 2019 Nov;123(5):488-493.e2. doi: 10.1016/j.anai.2019.08.007. Epub 2019 Aug 20.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): August 18, 2017
• Study Completion (Actual): August 18, 2017

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimated): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nut and Peanut Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate; Food Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity
• Other Study ID Numbers: PEPITES