Clinical trial NCT02636699: Efficacy and Safety of Viaskin Peanut in Children With Immunoglobulin E (IgE)-Mediated Peanut Allergy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peanut Allergy
Lead sponsor: DBV Technologies
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 500
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in Percentages of Treatment Responders at Month 12; Analyzed in the Overall Population
timeFrame: At Month 12
Secondary outcomes:
measure: Difference in Percentages of Treatment Responders at Month 12; Analyzed in Each Screening Eliciting Dose (ED) Subgroup
timeFrame: At Month 12
measure: Cumulative Reactive Dose (CRD) of Peanut Protein at Baseline and Month 12
timeFrame: Baseline and Month 12
Other outcomes:
measure: Relative Change From Baseline in Peanut-specific Immunoglobulin E (IgE) Over Time
timeFrame: Baseline and Months 3, 6 and 12
measure: Relative Changes From Baseline in Peanut-specific Immunoglobulin G4 Subtype (IgG4) Over Time
timeFrame: Baseline and Months 3, 6 and 12
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: San Diego
country: United States
facility: University of California, Rady Children's Hospital
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens' Hospital
state: Massachusetts
city: New York
country: United States
facility: Jaffe Food Allergy Institute
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina - Chapell Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: ASTHMA, Inc.
state: Washington
city: Brisbane
country: Australia
facility: Allergy Medical
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
city: Sydney
country: Australia
facility: Children's Hospital Westmead
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Mississauga
country: Canada
facility: Cheema Research Inc.
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Allergy Asthma Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research Inc.
state: Ontario
city: Montréal
country: Canada
facility: CHUM & CHU Sainte-Justine
state: Quebec
city: Quebec
country: Canada
facility: Centre de Recherche Appliquée en Allergie de Québec (CRAAQ)
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: St.-Marien-Hospital
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Cork
country: Ireland
facility: Clinical Investigations Unit
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
Study officials:
affiliation: Children's Hospital Colorado
name: David M Fleischer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.