A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED PHASE III PIVOTAL TRIAL TO ASSESS THE EFFICACY AND SAFETY OF PEANUT EPICUTANEOUS IMMUNOTHERAPY WITH VIASKIN(RegisteredTM) PEANUT IN PEANUT-ALLERGIC CHILDREN (PEPITES STUDY)
- Children’s Medical Center (Dallas, Plano, Southlake)
John Bird, M.D.
This is a 12 month, phase iii, double-blind, placebo-controlled, randomized study to assess the efficacy and safety of the peanut patch, dosed at 250 [MiCRo-SYMBoL]g
peanut protein (per patch). The study will enroll peanut-allergic children ages 4-11. 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 maximum 6-week 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 300 mg peanut protein. Subjects who react at or below the dose of 300 mg peanut protein are considered eligible. Randomization of eligible subjects will occur in a 2:1 ratio to Viaskin[RegisteredTM] Peanut dosed at 250 [MiCRo-SYMBoL]g 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 1 mg, 3 mg or 10 mg;
* Stratum 2: children with a screening eD of 30 mg, 100 mg or 300 mg.
The randomization scheme will ensure that the ratio of active treatment to placebo is maintained in each stratum.
Subjects randomized in the study and consenting for the genetic analysis on a voluntary basis will be assessed for mutations in the filaggrin gene. Subjects' participation for this genetic analysis will be optional, however the sponsor has requested that the uTSW site not participate in the genetic portion of the study. Subjects will apply a Viaskin[RegisteredTM] 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. Subjects will undergo other efficacy parameter assessments at Months 3, 6 and 12, including immunological changes in peanut-specific
immunoglobulin e (ige) and immunoglobulin G4 subtype (igG4) and skin prick tests (SPTs).
Key assessments of global safety will be performed at each study visit by the investigators, including skin observation of the patch areas of application
(inter-scapular area of the back), spirometry, peak expiratory flow (PeF) measurements, vital signs, physical examinations and clinical laboratory
assessments. atopic dermatitis will also be assessed at baseline and at Months 3, 6 and 12 using the SCoRaD (Scoring atopic dermatitis), for which
specific training will be provided for better use and accurate assessment. in between visits, the severity of local skin reactions will be assessed on a
daily basis by the subjects (parents/guardians) in their diary for at 6 months. any other adverse events (aes), local skin reactions occurring after
the first 6 months of treatment and any concomitant medications will also be reported in the diary by the subjects and this will be reviewed by the site
medical staff at each patient visit.
after completion of the PePiTeS study, all subjects, including the placebo subjects, will be offered the opportunity to participate in an open-label extension study to receive Viaskin[RegisteredTM] Peanut 250 [MiCRo-SYMBoL]g for 24 additional months of treatment. Subjects who will decide to roll-over into the extension study will have their last PePiTeS study visit at Visit 11 and they will start the extension study at that visit. Subjects who decide not to roll-over into the extension study will continue their visit schedule up to Visit 12.
Subjects will be enrolled in this study only if they meet all of the following criteria:
1. Male or female children aged 4 through 11 years at Visit 1;
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. Signed informed consent of parents/guardians of the child and child[Single Quote]s assent (for
children >=7 years of age or as per the country-specific regulations);
4. Negative urine pregnancy test for female subjects of childbearing potential. Female
subjects of childbearing potential must agree and commit to use effective medical
methods of contraception for the entire duration of their participation in the study.
Sexual abstinence will be accepted as an effective method of contraception;
5. Peanut-specific IgE level (ImmunoCAP system) >0.7 kU/L;
6. Positive peanut SPT with a largest wheal diameter:
a. >=6 mm for children 4 through 5 years of age at Visit 1,
b. >=8 mm for children 6 years and above at Visit 1;
7. Positive DBPCFC at <=300 mg peanut protein: the ED of peanut protein during the
entry/screening DBPCFC is capped to 300 mg, as in subjects must have objective
IgE-mediated symptoms to peanut leading to stopping the challenge at <=300 mg
8. Ability to perform spirometry in accordance with the American Thoracic Society (ATS) guidelines 2007 (39) for subjects >=6 years of age. Ability to perform peak expiratory flow (PEF) measurements for subjects >=5 years of age. Subjects from 6 to 8 years of age who have documented inability to adequately perform spirometry can perform the PEF measurement instead. Subjects 4 years of age can be enrolled if they had no clinical features of moderate or severe persistent asthma1 within 1 year prior to visit 1.
9. Subject and/or parents/guardians willing to comply with all study requirements
during the subject[Single Quote]s participation in the study.