| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of peanut allergy in adults and children age 6 years and older with documented hypersensitivity to peanut. The induction of clinical desensitization to peanut in patients allergic to peanut should reduce the risk of anaphylaxis in case of accidental exposure to small amounts of peanut proteins. |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10034202 |
| E.1.2 | Term | Peanut allergy |
| E.1.2 | System Organ Class | 100000004870 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the efficacy of several doses of Viaskin® Peanut to significantly desensitize peanut-allergic subjects to peanut after 12 months of Specific Immunotherapy by the cutaneous/epicutaneous route (i.e. Epicutaneous Immunotherapy or EPIT). |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety of a long-term EPIT with Viaskin® Peanut. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. 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.
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. Sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age.
5. Ability to perform spirometry maneuvers in accordance with the American Thoracic Society guidelines (2005) for subjects 9 years of age and above. For those subjects below 9 years of age who cannot perform spirometry, peak expiratory flow (PEF) will be considered instead.
6. Subjects and/or parents/guardians willing to comply with all study requirements during their participation in the study.
7. 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).
|
|
| E.4 | Principal 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) for subjects 9 years of age and above. For subjects below 9 years of age who cannot perform spirometry, the PEF < 80% of predicted will be considered instead.
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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 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 the initial eliciting dose. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| at the 12-month time point (end of the study) |
|
| E.5.2 | Secondary end point(s) |
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:
11. Adverse events (AEs) by system organ class and relatedness to Viaskin® Peanut (all subjects and by age strata).
12. Incidence, duration and severity of local Viaskin® Peanut-induced AEs as assessed by the subjects (all subjects and by age strata).
13. Systemic allergic symptoms and relatedness to Viaskin® Peanut (all subjects and by age strata).
14. Serious AEs (SAEs) and relatedness to Viaskin® Peanut (all subjects and by age strata).
15. Severity of AEs or SAEs elicited during the study and during the DBPCFCs at entry and after treatment (all subjects).
16. Laboratory data, physical examinations and vital signs (all subjects).
17. Spirometry results (all subjects and by age strata).
18. 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.
19. 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.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the 12-month time point (end of the study)
2. at the 12-month time point (end of the study)
3. at the 12-month time point (end of the study)
4. at the 12-month time point (end of the study)
5. at the 3, 6 and 12-month time points
6. at the 3, 6 and 12-month time points
8. at the 3, 6 and 12-month time points
9. at the 12-month time point (end of the study)
10. at the 3, 6 and 12-month time points
11 to 19: at the 12-month time point (end of the study)
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
