The objectives of this follow-up/extension study of the VIPES study are:• To assess the efficacy of Viaskin® Peanut after up to 36 months of Epicutaneous Immunotherapy (EPIT) in peanut-allergic subjects.• To evaluate the safety of long-term…
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Brief title
Condition
- Food intolerance syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The OLFUS-VIPES study will have two treatment groups: Treatment Group 1 will
consist of subjects who had received placebo in the VIPES study; Treatment
Group 2 will consist of subjects who had received Viaskin® Peanut in the VIPES
study.
Efficacy Endpoints:
The following efficacy endpoints will be assessed:
• At Month 12 in the OLFUS-VIPES study and by treatment group, the proportion
of subjects with a peanut protein eliciting dose equal to or greater than 1000
mg peanut or with a >=10-fold increase of the eliciting dose compared to their
baseline eliciting dose observed in the VIPES study. Subjects having received
active treatment with Viaskin® Peanut for a total of 12 months (Treatment Group
1) and a total of 24 months (Treatment Group 2) will be analyzed separately.
• At Month 24 in the OLFUS-VIPES study and by treatment group 1 or 2, the
proportion of subjects with a peanut protein eliciting dose equal to or greater
than 1000 mg peanut or with a >=10-fold increase of the eliciting dose compared
to their baseline eliciting dose observed in the VIPES study. Subjects having
received active treatment with Viaskin® Peanut (DBV712) for a total of 24
months and a total of 36 months (since the VIPES study) will be analyzed
separately.
• The proportion of subjects unresponsive (i.e. showing no objective symptoms
during DBPCFC) to a cumulative dose of 1440 mg peanut protein or above at Month
12 and Month 24 in the OLFUS VIPES study.
• The 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 1440 mg peanut protein or above at Month 26.
• The median and mean cumulative reactive dose of peanut protein at Month 12
and Month 24 by treatment group.
• The change from baseline in peanut-specific IgE and IgG4 at Month 6, Month
12, Month 18 and Month 24 by treatment group.
• The 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.
• 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.
Safety Endpoints:
The following safety endpoints will be assessed:
• Adverse events (AEs) by system organ class, severity and relatedness to
Viaskin® Peanut (all subjects and by age strata).
• Serious AEs (SAEs) by system organ class, severity and relatedness to
Viaskin® Peanut (all subjects and by age strata).
• Systemic allergic symptoms and relatedness to Viaskin® Peanut (all subjects
and by age strata).
• Severity of AEs or SAEs elicited during the study and the DBPCFCs (all
subjects).
• Laboratory data, physical examinations and vital signs (all subjects).
• Spirometry or Peak Expiratory Flow (PEF) results (all subjects).
Secondary outcome
Exploratory Criteria:
• Enumeration and characterization of reactions triggered by accidental
consumption of peanut during the follow-up study.
• Analysis of *Risk-taking behavior* of subjects (voluntary peanut consumption)
during the follow-up study.
Background summary
The Investigational New Drug, Viaskin® Peanut (DBV712), is a dry deposit of a
formulation of peanut Protein extract intended for EPIT. EPIT is an emerging
allergen-Specific ImmunoTherapy (known as SIT) approach for the treatment of
atopic diseases. Recently, EPIT was successfully used for the treatment of
grass pollen allergy (21), and also tested in a pilot 3-month clinical study in
IgE-mediated cow*s milk allergy conducted in France (22). The Investigational
New Drug Viaskin® Peanut is a ready-touse and easy-to-administer form
ofallergen immunotherapy. Viaskin® Peanut is intended to induce clinical
desensitization/tolerization to peanut in subjects moderately to severely
allergic to peanut. Viaskin® Peanut includes the natural and complete set of
peanut proteins that can interact with the local antigen presenting cells such
as the epidermic Langerhans and dendritic cells and can initiate the process of
clinical desensitization/tolerization. Moreover, by utilizing the epicutaneous
route of administration, Viaskin® Peanut is able to initiate these
immunomodulatory processes while minimizing the potential
safety concerns associated with systemic exposure to food allergens.
Based on the results of the Phase Ib study, the doses of 50 µg, 100 µg and 250
µg are considered for this Phase IIb study for all ages of patient population,
i.e. 18 to 55 years of age.
Study objective
The objectives of this follow-up/extension study of the VIPES study are:
• To assess the efficacy of Viaskin® Peanut after up to 36 months of
Epicutaneous Immunotherapy (EPIT) in peanut-allergic subjects.
• To evaluate the safety of long-term treatments with Viaskin® Peanut.
• To evaluate the sustained unresponsiveness to peanut after a period of 2
months without treatment in subjects showing desensitization to peanut after
EPIT with Viaskin® Peanut.
Study design
This is an open-label follow-up study or extension study for subjects who
previously were randomized and have completed the VIPES 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
and a peanut-free diet.
In Protocol 2.0 (incorporating Protocol Amendment 1), 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 µg peanut protein, regardless of
prior treatment (placebo, 50 µg, 100 µg or 250 µg Viaskin® Peanut) they were
receiving in the VIPES study.
Subjects who entered already the OLFUS-VIPES study under the initial protocol
design (Protocol Version 1.1 dated 27 May 2013) will all switch to receive the
250 µg dose at their protocol visit at Month 6 (Visit 3) or at Month 12 (Visit
4) after the approval of Amendment 1 at their sites.
The transition from the VIPES study to the OLFUS-VIPES study or the transition
from the initial OLFUS-VIPES design to the amended OLFUS-VIPES design will be
performed keeping the blinding in the VIPES study until the VIPES study results
are obtained. The same Interactive Web Response System (IWRS) used to allocate
treatment to subjects in the VIPES study will be used in the OLFUS-VIPES study.
Hence, all subjects should receive the 250 µg dose in the OLFUS-VIPES study but
none of them will be unblinded until the VIPES study is unblinded.
During the lifetime of the OLFUS-VIPES study, the VIPES study results will be
revealed and an optimal clinical dose of Viaskin® Peanut for future studies
will be determined.
However, in the OLFUS-VIPES study, all subjects would already be treated at the
250 µg dose at that time, and they will remain under the 250 µg dose to the end
of the study, whatever the optimal clinical dose is. This will prevent subjects
from having to switch to another dose again during the OLFUS-VIPES study.
After the overall 24 months of active treatment with Viaskin® Peanut, a period
of 2 months without treatment will be considered for those subjects being
assessed for sustained unresponsiveness.
Repeated daily application of Viaskin® Peanut will continue as in the VIPES
study, i.e. a new patch will be applied every 24 hours on the inner side of
both upper arms for adults (>=18 years) and adolescents (12-17 years), or on the
inter-scapular area of the back for children (7-11 years).
In order not to unblind the treatment arms until the results of the VIPES study
are known and to better assure safety in particular for placebo subjects
crossing over to receive the 250 µg dose of Viaskin® Peanut, the duration of
application of the Viaskin® Peanut patch will be progressively increased for
the first 2 weeks of treatment in all subjects entering the OLFUS VIPES study
(one week shorter than what was done at the start of the VIPES study): patches
will be applied for 6 hours every day during the first week, 12 hours every day
during the second week, and for the entire 24 hours of daily application from
the third week or the 15th day onwards.
Subjects enrolled in the OLFUS-VIPES study before approval of Protocol
Amendment 1 and who will switch to the 250 µg dose after Protocol Amendment 1
is approved may apply the new 250 µg patch for the whole 24 hours starting on
the very first day. They have been receiving Viaskin® Peanut at one of the
three doses for at least 6 months: no safety concerns are expected. However, at
the discretion of the Investigator, the 2-week period of progressive increase
of time of daily application described above may be repeated.
The first double-blind placebo-controlled food challenge (DBPCFC) in the
OLFUS-VIPES study will be conducted after 12 months of treatment up to a
cumulative dose of 5040 mg peanut protein.
The second DBPCFC in the OLFUS-VIPES study will be conducted after 24 months of
treatment for all subjects up to a cumulative dose of 5040 mg peanut protein.
- Subjects who react objectively below or at a cumulative dose of 1440 mg of
peanut protein during this second DBPCFC at 24 months in the OLFUS-VIPES study
will have their last visit at Visit 8 (Month 24 + 1 week).
- Subjects who are unresponsive to the cumulative dose of 1440 mg of peanut
protein or above during this second DBPCFC at 24 months in the OLFUS-VIPES
study will continue to a Month 26 visit as described below.
Subjects who are unresponsive at a cumulative dose of 1440 mg peanut protein or
above (unresponsiveness to the DBPCFC is defined as no objective reaction to
peanut protein), will be taken off treatment and will continue for an
additional 2 months without treatment and will continue their peanut-free diet.
This additional period will help to assess the **sustained unresponsiveness**
i.e. to study whether the subjects will maintain this level of unresponsiveness
to peanut protein even after 2 months without receiving any peanut EPIT
treatment.
The third DBPCFC in the study will then be conducted after a period of 2 months
without treatment, i.e. at Month 26 (Visit 9 and Visit 10), only for those
subjects who were unresponsive to a cumulative dose of 1440 mg peanut protein
or above at Month 24. Visit 10 will be the End of Study Visit for these
subjects.
Throughout the OLFUS-VIPES study period, subjects will be instructed to remain
on a peanut-free diet. The re-introduction or not of peanut into the subject*s
diet at the end of their participation in the study will be left to the
Investigator*s decision.
Intervention
Repeated daily application of Viaskin® Peanut will continue as in the VIPES
study, i.e. a new patch will be applied every 24 hours on the inner side of
both upper arms for adults (>=18 years) and adolescents (12-17 years), or on the
inter-scapular area of the back for children (7-11 years).
In order not to unblind the treatment arms until the results of the VIPES study
are known and to better assure safety in particular for placebo subjects
crossing over to receive the active treatment at the 250 µg dose of Viaskin®
Peanut, the duration of application of the Viaskin® Peanut patch will be
progressively increased for the first 2 weeks of treatment in all subjects
entering the OLFUS VIPES study (one week shorter than what was done at the
start of the VIPES study): patches will be applied for 6 hours every day during
the first week, 12 hours every day during the second week, and for the entire
24 hours of daily application from the third week or the 15th day onwards.
Study burden and risks
Patients with peanut allergy have to be watchful with food intake at all times.
We believe that the intended benefits outweigh the
possible disadvantages and burden. A number of study procedures that the
patient will undergo are standard procedures that is
done for these patients.
reu des Meuniers 80/84
Bagneux 92220
FR
reu des Meuniers 80/84
Bagneux 92220
FR
Listed location countries
Age
Inclusion criteria
1. Signed informed consent from adult subjects or parent(s)/guardian(s) of children <18 years + 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.
2. Adult and pediatric subjects (>=7 years) who completed the VIPES study, with a mandatory and
documented DBPCFC at Month 12 in the VIPES study.
3. Negative pregnancy test for women of childbearing potential at Visit 10 in the VIPES study.
4. 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.
5. Subjects and/or parents/guardians willing to comply with all study requirements during their
participation in the study.
Exclusion criteria
1. 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.
2. Pregnancy or lactation.
3. Females of childbearing potential planning a pregnancy in the coming 2 to 3 years.
4. Subjects who became allergic to chocolate or who do not want to consume the chocolate study challenge vehicle anymore.
5. Subjects who developed hypersensitivity to excipients of the Viaskin patches or of the food challenge formula used during the VIPES study.
6. 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.
7. Subjects with asthma that has evolved and now fulfills any of the criteria defined as follows:
a. 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.
b. at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months.
c. prior intubation for asthma in the past year.
8. Subjects receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
9. Subjects receiving or planning to receive anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy.
10. 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.
11. Subjects receiving or planning to receive any aeroallergen immunotherapy during their participation in the study.
12. Allergy or know history of reaction to Tegaderm® with no possibilities to use an alternative dressing approved by the Sponsor.
13. Subjects suffering from generalized dermatologic disease (e.g. severe atopic dermatitis, uncontrolled generalized eczema, ichthyosis vulgaris) with no intact zones to apply the Viaskin® patches.
14. Subjects or parent(s)/guardian(s) of subjects with obvious excessive anxiety and unlikely to cope with the conditions of a food challenge.
15. Past or current disease(s) which, in the opinion of the Investigator or the Sponsor, may affect the subject*s participation in this study, including but not limited to active eosinophilic gastrointestinal disorders, autoimmune disorders, immunodeficiency, malignancy, uncontrolled diseases (e.g. hypertension, psychiatric, cardiac), or other disorders (e.g. liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders).
16. Any new disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.
17. A history of drug or alcohol abuse while in the VIPES study.
18. 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.
19. Subjects unable to follow the protocol requirements.
20. Participation in another clinical intervention study in the past year, other than the VIPES study.
21. Subjects on any experimental drugs in the past year, other than those used in the VIPES study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001754-10-NL |
| ClinicalTrials.gov | NCT01955109 |
| CCMO | NL45417.041.13 |