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

• Study Type: Interventional
• Enrollment (Actual): 356
• 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
    • Charite Universitatsmedizin Berlin
  • Bonn, Germany, D-53115
    • St.-Marien-Hospital
  • Erlangen, Germany
    • Universitatsklinikum 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
• Genders Eligible for Study: All

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
Placebo Comparator: Placebo	Biological: Placebo; Cutaneous patch containing an inactive deposit manufactured to mimic peanut extract
Experimental: Viaskin Peanut 250mcg	Biological: Viaskin Peanut 250mcg; Peanut extract cutaneous patch; Other Names: DBV712

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 DBPCFCs to determine 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
Difference in Percentages of Treatment Responders at Month 12; Analyzed in Each Screening ED Subgroup	The DBPCFCs to determine 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
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

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

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 (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: September 17, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

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