Follow-up of the VIPES Study to Evaluate Efficacy and Safety of Viaskin Peanut in Adults and Children (OLFUS-VIPES)

• ClinicalTrials.gov Identifier: NCT01955109
• Recruitment Status: Completed
• First Posted: October 7, 2013
• Last Update Posted: January 25, 2018
• Sponsor: DBV Technologies
• Information provided by (Responsible Party): DBV Technologies

Tracking Information

• First Submitted Date: September 24, 2013
• First Posted Date: October 7, 2013
• Last Update Posted Date: January 25, 2018
• Study Start Date: September 2013
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2013)

Increase in the threshold dose of peanut protein during long-term treatment assessed by double-blind, placebo-controlled food challenges (DBPCFC) [ Time Frame: From baseline in the VIPES study to Month 12 and to Month 24 (end of treatment) in the OLFUS-VIPES study ]

At Month 12 and at Month 24 in the OLFUS-VIPES study and by treatment group, the proportion of subjects with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut protein or with a ≥10-fold increase of the eliciting dose compared to their baseline eliciting dose observed in the VIPES study. Subjects having received placebo in the VIPES study (Treatment Group 1) and subjects having received Viaskin Peanut in the VIPES study (Treatment Group 2) will be analyzed separately.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 9, 2015)

• Proportion of subjects unresponsive (i.e. showing no objective symptoms during DBPCFC) to a cumulative dose of 1,440 mg peanut protein or above at Month 12 and Month 24. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]
• Proportion of subjects with a sustained unresponsiveness (i.e. showing no objective symptoms during DBPCFC after a period of 2 months without treatment) to a cumulative dose of 1,440 mg peanut protein or above. [ Time Frame: Month 26 of the OLFUS-VIPES study ]
• Median cumulative reactive doses of peanut protein at Month 12 and Month 24 by treatment group. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]
• Change from baseline in peanut-specific IgE and IgG4 at Month 6, Month 12, Month 18 and Month 24 by treatment group. [ Time Frame: From baseline in the VIPES study to Month 6, to Month 12, to Month 18 and to Month 24 (end of treatment) in the OLFUS-VIPES study ]
• Change from baseline in the average wheal diameter during the skin prick testing (undiluted) at Month 6, Month 12, Month 18 and Month 24 by treatment group [ Time Frame: From baseline in the VIPES study to Month 6, to Month 12, to Month 18 and to Month 24 (end of treatment) in the OLFUS-VIPES study ]
• Change in the Quality of Life (the FAQLQ/FAIM) at Month 12 and Month 24 compared to Day 1 for those countries where the questionnaires were available, globally and by treatment group. [ Time Frame: From Day 1 in the OLFUS-VIPES study to Month 12 and Month 24 (end of treatment) ]
• Adverse events (AEs) by system organ class, severity and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Serious AEs (SAEs) by system organ class, severity and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Systemic allergic symptoms and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Severity of AEs or SAEs elicited during the study and the DBPCFCs (all subjects). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Physical examinations, vital signs and Peak Expiratory Flow (PEF) results (all subjects) [ Time Frame: At each of the 10 study visits ]
• Laboratory data, Spirometry (FEV1) results (all subjects). [ Time Frame: At 5 visits throughout the study ]
• Mean cumulative reactive doses of peanut protein at Month 12 and Month 24 by treatment group. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]

Original Secondary Outcome Measures (submitted: October 4, 2013)

• Proportion of subjects unresponsive (i.e. showing no objective symptoms during DBPCFC) to a cumulative dose of 1,444 mg peanut protein or above at Month 12 and Month 24. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]
• Proportion of subjects with a sustained unresponsiveness (i.e. showing no objective symptoms during DBPCFC after a period of 2 months without treatment) to a cumulative dose of 1,444 mg peanut protein or above. [ Time Frame: Month 26 of the OLFUS-VIPES study ]
• Median cumulative reactive doses of peanut protein at Month 12 and Month 24 by treatment group. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]
• Change from baseline in peanut-specific IgE and IgG4 at Month 12 and Month 24 by treatment group. [ Time Frame: From baseline in the VIPES study to Month 12 and to Month 24 (end of treatment) in the OLFUS-VIPES study ]
• Change from baseline in the average wheal diameter during the skin prick testing (undiluted) at Month 6, Month 12, Month 18 and Month 24 by treatment group [ Time Frame: From baseline in the VIPES study to Month 12 and to Month 24 (end of treatment) in the OLFUS-VIPES study ]
• Change in the Quality of Life (the FAQLQ/FAIM) at Month 12 and Month 24 compared to Day 1 for those countries where the questionnaires were available, globally and by treatment group. [ Time Frame: From Day 1 in the OLFUS-VIPES study to Month 12 and Month 24 (end of treatment) ]
• Adverse events (AEs) by system organ class, severity and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Serious AEs (SAEs) by system organ class, severity and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Systemic allergic symptoms and relatedness to Viaskin Peanut (all subjects and by age strata). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Severity of AEs or SAEs elicited during the study and the DBPCFCs (all subjects). [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
• Physical examinations, vital signs and Peak Expiratory Flow (PEF) results (all subjects) [ Time Frame: At each of the 10 study visits ]
• Laboratory data, Spirometry (FEV1) results (all subjects). [ Time Frame: At 5 visits throughout the study ]
• Mean cumulative reactive doses of peanut protein at Month 12 and Month 24 by treatment group. [ Time Frame: Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study ]

Current Other Pre-specified Outcome Measures (submitted: October 4, 2013)

• Occurrence of reactions triggered by accidental consumption of peanut during the OLFUS-VIPES study. [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
  Frequency of accidental consumption, conditions around the accidental consumption, estimated quantity consumed at each occurrence, and associated reactions and severity of reactions
• Occurrence of "risk-taking behaviors" of subjects towards peanut during the OLFUS-VIPES study. [ Time Frame: Throughout the treatment period (24 months) and the 2-month period without treatment ]
  Frequency of deliberate consumption of peanut, conditions around the consumption, estimated quantity consumed at each occurrence and associated reactions with these consumptions.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Follow-up of the VIPES Study to Evaluate Efficacy and Safety of Viaskin Peanut in Adults and Children
• Official Title: Open-label Follow-up Study of the VIPES Study to Evaluate Long-term Efficacy and Safety of the Viaskin Peanut

Brief Summary

The objectives of this open-label follow-up study for subjects who previously were randomized and have completed the VIPES study for the treatment of peanut allergy, are:

• To assess the efficacy of Viaskin Peanut after up to 36 months of treatment.
• To evaluate the safety of long-term treatment with Viaskin Peanut.
• To evaluate sustained unresponsiveness to peanut after a period of 2 months without treatment in subjects showing desensitization to peanut after 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%. So far, there is no approved treatment of peanut allergy. 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 OLFUS-VIPES study is an open-label follow-up study for subjects who previously were randomized and have completed the VIPES efficacy and safety study. Subjects will be offered enrollment in this follow-up study to receive an additional 24 months of Viaskin Peanut treatment followed by a period of 2 months without treatment while maintaining a peanut-free diet.

The trial will be conducted at the same sites as the VIPES study 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.

According to the current amended study protocol, all subjects enrolling into the OLFUS-VIPES study after having completed the VIPES study will receive the highest dose of Viaskin Peanut, i.e. 250 mcg peanut protein, regardless of prior treatment (placebo, 50 mcg, 100 mcg or 250 mcg Viaskin Peanut) they were receiving in the VIPES study. Subjects who already enrolled into the OLFUS-VIPES study under the initial protocol design will all switch to receive the 250 mcg dose at Month 6 or at Month 12 of treatment in the OLFUS-VIPES study upon approval of the amended protocol at their sites. The study will remain blinded for all subjects until the VIPES study is unblinded. All subjects completing the OLFUS-VIPES study should receive overall 24 months of active treatment followed by a period of 2 months without treatment for those subjects being assessed for sustained unresponsiveness.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Peanut Allergy

Intervention

Biological: Viaskin Peanut 250 mcg

Subjects epicutaneously administered for 24 hours every 24 hours with a patch containing 250 mcg peanut proteins as whole peanut extract

Study Arms

Experimental: Viaskin Peanut 250 mcg

Intervention: Biological: Viaskin Peanut 250 mcg

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 9, 2015): 171
• Original Estimated Enrollment (submitted: October 4, 2013): 220
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult and pediatric subjects (≥7 years) who completed the VIPES study, with a mandatory and documented DBPCFC at Month 12 in the VIPES study.
• Signed informed consent from adult subjects or parent(s)/guardian(s) of children <18 years and children's assent for children >7 years or as per country-specific regulations or laws. This consent should be signed no later than Visit 11 in the VIPES study.
• Negative pregnancy test for women of childbearing potential at Visit 10 in the VIPES study.
• Female subject of childbearing potential 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. Documented sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age.
• Subjects and/or parents/guardians willing to comply with all study requirements during their participation in the study.

Exclusion Criteria:

• Severe reaction during the DBPCFC at Month 12 in the VIPES study, defined as need for intubation, hypotension persisting after epinephrine administration, and/or the need for more than two doses of epinephrine.
• Pregnancy or lactation.
• Females of childbearing potential planning a pregnancy in the coming 2 to 3 years.
• Subjects who became allergic to chocolate or who do not want to consume the chocolate study challenge vehicle anymore.
• Subjects who developed hypersensitivity to excipients of the Viaskin patches or of the food challenge formula used during the VIPES study.
• 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 with asthma that has evolved and now fulfills any of the criteria defined as follows:

  • 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.
  • at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months.
  • prior intubation for asthma in the past year.
• Subjects receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
• Subjects receiving or planning to receive anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy.
• Subjects receiving or planning to receive any type of immunotherapy to any food (e.g. oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) during their participation in the study.
• Subjects receiving or planning to receive any aeroallergen immunotherapy during their participation in the study.
• Allergy or known history of reaction to Tegaderm® with no possibilities to use an alternative dressing approved by the sponsor.
• Subjects suffering from generalized dermatologic disease (e.g. severe atopic dermatitis, uncontrolled generalized eczema, ichthyosis vulgaris) with no intact zones to apply the patches.
• Any new disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.
• A history of non compliance in the VIPES study. Non compliance is defined as subjects not applying the patch at all for 60 days or more (this can be either consecutive or intermittent non-application of the patches) during the whole VIPES study duration
• Participation in another clinical intervention study in the past year, other than the VIPES study.
• Subjects on any experimental drugs in the past year, other than those used in the VIPES study.

Other inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 56 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Netherlands, United States

Administrative Information

• NCT Number: NCT01955109
• Other Study ID Numbers: OLFUS-VIPES
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: DBV Technologies
• Study Sponsor: DBV Technologies
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: DBV Technologies
• Verification Date: January 2018