· To determine the efficacy of several doses of Viaskin® Peanut to significantlydesensitize peanut-allergic subjects to peanut after 12 months of EPIT treatment .· To evaluate the safety of a long-term EPIT with Viaskin® Peanut.
ID
Source
Brief title
Condition
- Food intolerance syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint will be the percentage of treatment responders
for each active
treatment compared to placebo. A treatment responder is defined as a subject
with a peanut
protein eliciting dose equal to or greater than 1,000 mg peanut proteins based
on the results
of the DBPC peanut challenge after 12 months of treatment or a subject with a >=
10-fold
increase of the eliciting dose at 12 months, compared to their initial
eliciting dose.
Secondary outcome
Secondary Efficacy Endpoints:
The following secondary efficacy endpoints will be assessed:
1. The mean eliciting doses of peanut proteins at Month 12 in the 50 µg, 100 µg
and 250 µg groups versus the placebo group.
2 The mean cumulative reactive dose of peanut proteins at Month 12 in the 50
µg, 100 µg and 250 µg groups versus the placebo group.
3 The change in the severity of symptoms elicited during the peanut DBPCFCs
from baseline to Month 12 for each treatment group. Symptoms will be graded
according to the Oral Food Challenge (OFC) Symptom Score Sheet (Appendix 3)
described by the Work Group Report on
OFC testing (1).
4 Time of appearance of the very first objective symptom during the DBPCFC at
Month 12 in the 50 µg, 100 µg and 250 µg groups versus the placebo group.
5.The change in peanut end point titration by skin prick testing at baseline
and at Months 3, 6 and 12.
6. The change in peanut-specific IgE, and immunoglobulin G subtype 4 (IgG4) at
baseline and at Months 3, 6 and 12.
7 The correlation between the presence of peanut protein component(s) and
response to Viaskin® Peanut immunotherapy.
8 The mean fold reduction of basophil activation, assessed by CD203c
expression, at Months 3, 6 and 12. These results will be correlated with the
primary efficacy criterion.
9. Primary efficacy endpoint in each age stratum.
10. Secondary efficacy endpoints in each age stratum for the mean eliciting
dose in each treatment group, time of appearance of the 1st objective symptom,
for the change in peanut-specific IgE and in IgG4 and the mean fold reduction
of basophil activation of CD203c expression.
Safety Endpoints:
The following safety criteria will be determined:
1. Adverse events (AEs) by system organ class and relatedness to Viaskin®
Peanut (all subjects and by age strata).
2. Incidence, duration and severity of local Viaskin® Peanut-induced AEs as
assessed by the subjects all subjects and by age strata).
3. Systemic allergic symptoms and relatedness to Viaskin® Peanut (all subjects
and by age strata).
4. Serious AEs (SAEs) and relatedness to Viaskin® Peanut (all subjects and by
age strata).
5. Severity of AEs or SAEs elicited during the study and during the DBPCFCs at
entry and after treatment (all subjects).
6. Laboratory data, physical examinations and vital signs (all subjects).
7. Spirometry results (all subjects and by age strata).
8. Safety sub-analysis in subjects with mutations in the filaggrin gene versus
wild type subjects on the following parameters: Incidence, duration and
severity of local Viaskin® Peanut-induced AEs, systemic allergic symptoms
related to Viaskin® Peanut, SAEs related to Viaskin® Peanut,
spirometry results.
Specific reactions triggered by an accidental consumption of peanut and the
conditions around that accidental consumption will be collected. These AEs will
be classified and analyzed separately.
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-to-use 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
· To determine the efficacy of several doses of Viaskin® Peanut to significantly
desensitize peanut-allergic subjects to peanut after 12 months of EPIT
treatment .
· To evaluate the safety of a long-term EPIT with Viaskin® Peanut.
Study design
This is a 12-month double-blind, placebo-controlled,
randomized trial to study the efficacy and safety of Viaskin® Peanut, an
allergen extract of peanut
administered epicutaneously using the Viaskin® epicutaneous delivery system in
subjects from 18 to 55
years old with a history of immediate hypersensitive reaction to peanut
protein. The trial will be conducted
at approximately 20-25 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 doubleblind
placebo-controlled food challenge (DBPCFC) in adult subjects. Three doses
of peanut proteins, i.e. 50 µg, 100 µg and 250 µg per patch will be evaluated
in the study.
Following the confirmation of peanut allergy at screening with a
dose-escalating DBPCFC and provided
that they reacted with an eliciting dose below or equal to 300 mg peanut
proteins, subjects will be
randomized in a 1:1:1:1 ratio into four different treatment groups, including
50 µg, 100 µg and 250 µg
peanut proteins versus placebo. Treatment will last 12 months. Each subject
will undergo two DBPCFCs:
one at screening and one at 12 months at the end of the treatment period. Doses
of peanut proteins will be
given during the challenge every 30 minutes starting with a starting dose of 1
mg peanut proteins and
proceeding up to a highest dose of 2,000 mg of peanut proteins for the
challenge conducted at the end of
treatment.
In addition to DBPCFC assessments, subjects will undergo other efficacy
parameter assessments at months
3, 6 and 12 including skin prick tests (SPTs), titrated SPTs, determination of
the changes in immunological
markers and basophil activation tests. Key assessments of safety, will be
performed at each study visit by
the investigators including spirometry, peak flow measurements, vital signs,
physical
examinations, clinical laboratory assessments. In between visits, subjects will
report safety data on the diary
cards.
A follow-up visit will be performed 2 weeks after completion of treatment and
after the last DBPCFC only for subjects who do not roll-over into the follow-up
study (called OLFUS-VIPES study for Open- Label Follow-Up Study of VIPES). All
subjects who completed the VIPES study up to Visit 11 (inclusive) will be
eligible for participation in the OLFUS-VIPES study. At Visit 11, eligible
subjects who have decided to enroll into the OLFUS-VIPES study can roll-over
into the OLFUS-VIPES study, unless in the opinion of the investigator, it is
not in the best interest of the subjects to continue receiving EPIT with
Viaskin® Peanut.. Subjects who roll-over into the OLFUS-VIPES study will have
their last visit at Visit 11 in VIPES. Those subjects who do not roll-over into
the OLFUS-VIPES study will have their last visit at Visit 12 as initially
planned. In total, during this study, subjects who roll-over into the
OLFUS-VIPES study will be required to attend 11 study visits and subjects who
do not roll-over into the OLFUS-VIPES study will be required to attend 12 study
visits.
Intervention
/
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.
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FR
Listed location countries
Age
Inclusion criteria
1. Peanut-allergic subjects between 18 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.
2. Peanut-specific immunoglobulin E (IgE) level (Phadia CAP-system) > 0.7 kU/L AND a positive peanut SPT with a largest wheal diameter >= 8 mm.;3. Positive 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.;4. 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.
5. Ability to perform spirometry maneuvers in accordance with the American Thoracic Society guidelines (2005) .
6. Subjects willing to comply with all study requirements during their participation in the study.;7. Signed informed consent from adult subjects.
Exclusion criteria
1. Subjects with a history of severe anaphylaxis to peanut with the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence) (see Appendix 2: Anaphylaxis Staging System).;2. Pregnancy or lactation.;3. Forced expiratory volume in one second (FEV1) < 80% of the predicted value at screening (Visit 1).
4. Subjects who did not react at or below the dose of 300 mg of peanut proteins during the DBPCFC at screening.;5. Subjects allergic to chocolate or who do not consume chocolate.;6. Subjects reacting objectively to the placebo formula at screening.;7. 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.;8. Subjects with symptomatic allergy to pollens whose symptoms during the corresponding pollen season might interfere with the recording of symptoms during the DBPCFC, if the DBPCFC is conducted during the pollen season. The Investigator will have to ensure that the period for conducting the DBPCFC for such a subject will be outside of the pollen season.;9. 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. ;10. Subjects treated with systemic long-acting corticosteroids (depot corticosteroids) within 12 weeks prior to Visit 1 and/or systemic short-acting corticosteroid within 4 weeks prior to Visit 1 or any systemic corticosteroid at screening. ;11. Subjects with asthma 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 (See Appendix 5: dosages of inhaled corticosteroids); ;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 two years.;12. Subjects on β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy. ;13. Subjects undergoing any type of immunotherapy to any food (oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) within one year prior to Visit 1.;14. Subjects presently on aeroallergen immunotherapy and unwilling or unable to discontinue.;15. 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 Visit 1.;16. 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 Viaskins. ;17. Subjects (or parents of subjects) with obvious excessive anxiety and unlikely to cope with the conditions of a food challenge.;18. 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, uncontrolled diseases (hypertension, psychiatric, cardiac), or other disorders (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders).;19. Any disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.;20. Subjects unable to follow the protocol and the protocol requirements.;25. Participation in another clinical intervention study in the three months prior to Visit 1.
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
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-002550-32-NL |
| CCMO | NL38911.041.12 |