Clinical trial NCT01675882: Efficacy and Safety of Several Doses of Viaskin Peanut in Adults and Children With Peanut Allergy
Official title: A Double-blind, Placebo-controlled, Randomized Trial to Study the Viaskin Peanut's Efficacy and Safety for Treating Peanut Allergy in Children and Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peanut Allergy
Keywords: Food allergy
Immediate hypersensitivity
Whole peanut extract
Allergenic product
Specific Immunotherapy
Epicutaneous Immunotherapy (EPIT)
Lead sponsor: DBV Technologies
Sponsor class: INDUSTRY
First posted: 2012-08-30
Enrollment: 221
Sex: ALL
Minimum age (years): 6
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this dose-finding study for the treatment of peanut allergy are:

* To determine the efficacy of 3 doses of Viaskin Peanut (50 mcg ,100 mcg and 250 mcg peanut protein per patch) to significantly desensitize peanut-allergic subjects to peanut after 12 months of treatment.
* To evaluate the safety of a long-term treatment with Viaskin Peanut.

Detailed description: Peanut allergy is a common allergy in the United States, with a prevalence in the general population as high as 1%. Peanut allergy management is based on strict peanut avoidance and injectable epinephrine after the allergic systemic reactions have started. Specific Immunotherapy methods currently available have shown some limitations in their use because of safety issues. Hence, there is an important unmet medical need for efficient and safe treatment of peanut allergy.

DBV Technologies has developed an epicutaneous delivery system, called Viaskin, a method based on delivering precise quantity of the allergen on the upper layers of the skin. Avoiding contact between the allergen and the bloodstream should confer to epicutaneous immunotherapy (EPIT) a higher level of safety as systemic reactions should be circumvented

The VIPES study is a 12-month double-blind, placebo-controlled,randomized trial to study the efficacy and safety of Viaskin Peanut in subjects from 6 to 55 years old with a history of immediate hypersensitive reaction to peanut protein.

The trial will be conducted at sites with investigators and staff trained and experienced in the diagnosis and the management of peanut allergy and anaphylaxis, and who are capable of performing a double-blind placebo-controlled food challenge (DBPCFC) in adult and/or pediatric subjects. Three doses of peanut proteins, i.e. 50 mcg, 100 mcg and 250 mcg will be evaluated for the study. Following the confirmation of peanut allergy at screening, subjects will be randomized in a 1:1:1:1 ratio into four different treatment groups, including 50 mcg, 100 mcg and 250 mcg peanut protein or placebo. Treatment will be comprised of daily applications of Viaskin Peanut or placebo patch for 12 months. Each subject will undergo two DBPCFCs: one at screening and one at Month 12. A follow up visit will be performed 2 weeks after completion of treatment and the last DBPCFC.

Eligibility criteria: Inclusion Criteria:

* Peanut-allergic subjects between 6 and 55 years of age, with a well-documented medical history of systemic reactions after ingestion of peanut and currently following a strict peanut-free diet.
* Peanut-specific immunoglobulin E (IgE) level (Phadia CAP-system) \> 0.7 kU/L and a positive skin prick test to peanut with a largest wheal diameter ≥ 8 mm
* Positive double-blind placebo-controlled food challenge (DBPCFC) at ≤ 300 mg of peanut proteins: the eliciting dose of peanut proteins during the DBPCFC is capped at 300 mg, i.e. subjects must react to peanut before reaching or at the dose of 300 mg peanut proteins.
* Negative pregnancy test for women of childbearing potential. Females of childbearing age must use effective methods of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age.
* Ability to perform spirometry maneuvers in accordance with the American Thoracic Society guidelines (2005) for subjects 9 years of age and above Subjects below 9 years of age can perform peak expiratory flow (PEF) instead.
* Willing to comply with all study requirements during their participation in the study.
* Provide signed informed consent and assent as appropriate.

Exclusion Criteria:

* Subjects with a history of severe anaphylaxis to peanut with the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence).
* Pregnancy or lactation.
* FEV1 \<80% of the predicted value at screening for subjects 9 years of age and above. PEF \< 80% of predicted for subjects below 9 years of age.
* Subjects who did not react at or below the dose of 300 mg of peanut proteins during the DBPCFC at screening.
* Known allergy or known hypersensitivity to placebo excipients either of the Viaskin patches or of the food challenge formulas.
* Subjects reacting objectively to the placebo formula at screening.
* Severe reaction during the screening food challenge, defined as need for intubation, hypotension persisting after epinephrine administration, or the need for more than two doses of epinephrine.
* Inability to discontinue short-acting antihistamines for three days or long-acting antihistamines for five to seven days (depending on half-life) prior to skin prick testing or food challenges.
* Subjects treated with systemic long-acting corticosteroids (depot corticosteroids) within 12 weeks prior to the screening visit and/or systemic short-acting corticosteroid within 4 weeks prior to the screening visit or any systemic corticosteroid at screening.
* Subjects with asthma defined as follows:

  1. uncontrolled persistent asthma by National Asthma Education and Prevention Program Asthma guidelines (2007) or by Global Initiative for Asthma (2011) or being treated with combination therapy of medium dose inhaled corticosteroid with a long acting inhaled β2-agonists;
  2. at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months;
  3. prior intubation for asthma in the past two years.
* Subjects on β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
* Subjects undergoing any type of immunotherapy to any food within one year prior to the screening visit.
* Subjects presently on aeroallergen immunotherapy and unwilling or unable to discontinue.
* Subjects currently treated with anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy within one year prior to the screening visit.
* Allergy or known history of reaction to Tegaderm®.
* Subjects suffering from generalized dermatologic diseases (e.g. severe atopic dermatitis, uncontrolled generalized eczema, keratosis pilaris, ichthyosis vulgaris) with no intact skin zones to apply the patches.
* Any disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.
* Participation in another clinical intervention study in the three months prior to the screening visit.
* Subjects on any experimental drugs or treatments.

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Treatment Responders at Month 12; Analyzed in Overall Population
timeFrame: At Month 12
Secondary outcomes:
measure: Percentage of Treatment Responders at Month 12; Analyzed in Children (6-11 Years of Age)
timeFrame: At Month 12
measure: Percentage of Treatment Responders at Month 12; Analyzed in Adolescents (12-17 Years of Age)
timeFrame: At Month 12
measure: Percentage of Treatment Responders at Month 12; Analyzed in Adults (18-55 Years of Age)
timeFrame: At Month 12
measure: Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Overall Population
timeFrame: At Month 12
measure: Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Children (6-11 Years of Age)
timeFrame: At Month 12
measure: Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Adolescents (12-17 Years of Age)
timeFrame: At Month 12
measure: Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Adults (18-55 Years of Age)
timeFrame: At Month 12
measure: Mean Cumulative Reactive Dose of Peanut Proteins at Month 12; Analyzed in Overall Population
timeFrame: At Month 12
measure: Change From Baseline in Severity of Symptoms Based on the Oral Food Challenge (OFC) Symptom Score Sheet at Month 12; Analyzed in Overall Population
timeFrame: Baseline and Month 12
measure: Number of Participants With an Average Wheal Diameter Ratio ≤0.5 and >0.5 at Each Skin Prick Test Dilution at Months 3, 6 and 12; Analyzed in Overall Population
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific Immunoglobulin E (IgE) at Months 3, 6 and 12; Analyzed in Overall Population
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Children (6-11 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Adolescents (12-17 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Adults (18-55 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific Immunoglobulin G Subtype 4 (IgG4) at Months 3, 6 and 12; Analyzed in Overall Population
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Children (6-11 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Adolescents (12-17 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Adults (18-55 Years of Age)
timeFrame: Baseline and Months 3, 6 and 12
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, Rady Childrens Hospital
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens' Hospital
state: Massachusetts
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 Dallas
state: Texas
city: Seattle
country: United States
facility: ASTHMA, Inc.
state: Washington
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
state: Ontario
city: Sainte-Foy
country: Canada
facility: Centre de Recherche Appliquée en Asthme et Allergie de Québec
state: Quebec
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Nice
country: France
facility: GCS des hôpitaux pédiatriques
city: Paris
country: France
facility: Hôpital Necker
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
city: Vandoeuvre-les-Nancy
country: France
facility: Hôpitaux De Brabois
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr2
city: Łódź
country: Poland
facility: Szpital Kliniczny UM
Study officials:
References:
citation: Lewis MO, Brown-Whitehorn TF, Cianferoni A, Rooney C, Spergel JM. Peanut-allergic patient experiences after epicutaneous immunotherapy: peanut consumption and impact on QoL. Ann Allergy Asthma Immunol. 2019 Jul;123(1):101-103. doi: 10.1016/j.anai.2019.04.006. Epub 2019 Apr 10. No abstract available.
citation: Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, Cheema AS, Leonard SA, Pongracic JA, Sauvage-Delebarre C, Assa'ad AH, de Blay F, Bird JA, Tilles SA, Boralevi F, Bourrier T, Hebert J, Green TD, Gerth van Wijk R, Knulst AC, Kanny G, Schneider LC, Kowalski ML, Dupont C. Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial. JAMA. 2017 Nov 14;318(18):1798-1809. doi: 10.1001/jama.2017.16591.