| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| 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 | 20.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10034202 | | E.1.2 | Term | Peanut allergy | | E.1.2 | System Organ Class | 10021428 - Immune system disorders | |
| 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 | The objectives of this follow-up study of the EPITOPE study are:
• To assess the clinical benefit of Viaskin Peanut after up to 3 years of epicutaneous immunotherapy (EPIT) to induce/maintain desensitization to peanut in peanut-allergic children;
• To evaluate the safety of long-term treatment with Viaskin Peanut in peanut-allergic children. | |
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Subjects will be enrolled into this study only if they meet all the following criteria:
1. Signed informed consent form (ICF) by the subject’s parent(s)/guardian(s). This consent should be signed after completion of Month 12 DBPCFC procedures in EPITOPE study, and before any procedure in EPOPEX study is started;
2. Subjects who completed the EPITOPE study, with a completed and documented DBPCFC at Month 12 (Visit 10 and Visit 11);
3. Parents/guardians and subjects willing to comply with all study requirements during the subject’s participation in the study. | |
| E.4 | Principal exclusion criteria | Subjects will be enrolled into this study only if they meet none of the following criteria:
1. Subjects who developed a severe anaphylactic reaction (see APPENDIX 5) during the DBPCFC at Month 12 (Visit 10 or Visit 11) in the EPITOPE study requiring a tracheal intubation or leading to a cardiac arrest and/or to coma. Other cases of severe anaphylaxis will be considered eligible to participate in the EPOPEX study;
2. Any clinically significant disease which in the judgment of the Investigator may preclude safe participation or strict compliance with the protocol procedures;
3. Generalized dermatologic disease (e.g., active atopic dermatitis, uncontrolled generalized active eczema, ichthyosis vulgaris) extending widely on the skin, especially on the back, with no intact zones to apply the patches;
4. Subjects who developed hypersensitivity to materials and/or excipients of the Viaskin® patch;
5. Subjects who developed hypersensitivity to excipients of the food challenge formula (other than peanut proteins) used in the EPITOPE study or confirmed allergy to apple;
6. Subjects who failed to complete the DBPCFC at Month 12 in the EPITOPE study due to any reason, including clear aversion to the food formula matrix;
7. Inability to discontinue short-acting antihistamines or long-acting antihistamines for the minimum wash-out periods required (depending on half-lives, as specified in APPENDIX 4) prior to the SPT or the DBPCFC;
8. Diagnosis of asthma that has evolved and now fulfills any of the criteria defined as follows:
- Uncontrolled asthma (as per Global Initiative for Asthma [GINA] 2018 guidelines (34); see APPENDIX 3);
- Asthma requiring controller treatment step 3 or higher (as per GINA 2018 guidelines (34): either moderate [double low dose] of inhaled corticosteroid [ICS], or association of ICS with leukotriene receptor antagonist [LTRA]; see APPENDIX 3);
- Prior intubation/mechanical ventilation for asthma in the past year.
Asthmatic subjects with the following treatment options are eligible:
- No controller treatment (GINA step 1);
- Controller treatment monotherapy (GINA step 2): daily or short-term course (intermittent) low dose ICS or LTRA.
9. Presence of more than 3 episodes of wheezing in the past year (each lasting more than 10 consecutive days, apart from colds) or presence of respiratory symptoms (wheezing, cough, heavy breathing) between these episodes, and/or other respiratory symptoms suggesting either undiagnosed asthma or asthma not controlled by asthma treatment (as per GINA 2018 guidelines (34)).
10. 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 past or 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).
11. Any disease in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.
12. Diagnosis of mast cell disorders including mastocytosis or urticaria pigmentosa as well as hereditary or idiopathic angioedema.
13. Subject receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
14. Subject who received in the past year or planning to receive anti-tumor necrosis factor drugs or anti-IgE drugs (e.g., omalizumab) any biologic immunomodulatory therapy, cyclosporine or other immunosuppressive drugs within. Topical calcineurin inhibitors are permitted.
15. Subject receiving or planning to receive any other type of immunotherapy to any food (e.g., oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) or any aeroallergen or venom immunotherapy during their participation in the study.
16. Subjects or parent(s)/guardian(s) with obvious excessive anxiety and unlikely to cope with the food challenge procedures or unable to follow the protocol requirements.
17. A history of high non-compliance during the EPITOPE study (i.e., subjects not applying the patches for 60 or more days in total and not applying the patches 30 or more consecutive days during the EPITOPE study) or subjects unable to perform the DBPCFC.
18. Current participation in another clinical study, other than the EPITOPE study.
19. Subjects being in any personal relationship or dependency with the Sponsor and/or the Investigator or the study staff. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | The following endpoints will be explored for the assessment of the sustained clinical benefit of Viaskin Peanut 250 μg after 1, 2 and 3 years of treatment in each group (VP+VP group, Placebo+VP group) and overall:
• Proportion of subjects reaching an ED ≥1000 mg peanut protein;
• Proportion of treatment responders, using the treatment response definition of the EPITOPE study, i.e. a subject is defined as a treatment responder if:
o The baseline ED was >10 mg peanut protein and the ED is ≥1000 mg peanut protein at the post-baseline double-blind placebo-controlled food challenges (DBPCFCs) or;
o The baseline ED was ≤10 mg and the ED is ≥300 mg peanut protein at the post-baseline DBPCFCs.
For the VP+VP group, the baseline ED is defined as the ED reached at the EPITOPE study entry.
For the Placebo+VP group, the baseline ED is the latest, valid ED in the EPITOPE study (i.e., Month 12).
• Proportion of subjects reaching a cumulative dose of at least 1444 mg peanut protein at the post-baseline DBPCFCs;
• Proportion of subjects reaching a cumulative dose of at least 3444 mg peanut protein at the post-baseline DBPCFCs;
• Proportion of subjects unresponsive (i.e., showing no symptoms leading to stopping the DBPCFC) to the highest dose of peanut protein (i.e. 2000 mg), which is the percentage of subjects who pass the post-baseline DBPCFCs;
• Mean and median CRD of peanut protein;
• Mean and median ED of peanut protein.
The following safety endpoints will be analyzed:
• Adverse Events and TEAEs by System Organ Class (SOC) and Preferred Term (PT);
• Treatment-emergent adverse events by maximum severity and by maximum duration and relatedness to the IP;
• Serious adverse events (SAEs) by SOC and PTs, maximum severity and relatedness to the IP;
• Treatment-emergent adverse events leading to treatment discontinuation;
• Local AESI (i.e., reactions at patch sites potentially leading to skin barrier disruption) and systemic AESIs (i.e., anaphylaxis, or systemic hypersensitivity reactions leading to epinephrine intake), whatever the causal relationship to the IP;
• Incidence, duration and maximum severity of local cutaneous reactions as assessed by the subjects;
• Incidence and severity of local cutaneous reactions as assessed by the Investigators;
• Laboratory data, physical examinations and vital signs;
• Spirometry results and peak expiratory flow (PEF) results.
The following of study procedure safety criteria will be assessed over 3 years of treatment:
• Symptoms elicited during the DBPCFCs by severity;
• Severity of symptoms score during the DBPCFCs;
• Serious AEs elicited during the DBPCFCs.
The safety endpoints will be evaluated in the overall Safety population using the rescheduling rules and by treatment group (VP+VP / Placebo+VP). | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | Refer to Sections 6.1 and 6.2 of the protocol. | |
| E.5.2 | Secondary end point(s) | The following other exploratory endpoints will be evaluated over 3 years of treatment in each group (VP+VP group, Placebo+VP group) and overall using the rescheduling rules:
• Total IgE, peanut-specific IgE and IgG4 levels and levels of IgE and IgG4 specific to peanut protein components (Ara h 1, Ara h 2, Ara h 3);
• Peanut Skin Prick Test (SPT) average wheal diameters;
• Description of the quality of life (QoL) questionnaires (Food Allergy Quality of Life Questionnaires [FAQLQ]/ Food Allergy Independent Measure [FAIM]/EQ-5D-5L) data and QoL scores;
• Enumeration and characterization of reactions triggered by accidental consumption of peanut and analysis of “risk-taking behavior” of subjects (voluntary peanut consumption) during the study;
• Epigenetic modifications of the promoters of some specific genes;
• Sensitization status to other allergens and their evolution over the study period;
• Scoring atopic dermatitis (SCORAD) index evolution over time. | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | Refer to Section 6.4 of the protocol. | |
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | | Australia | | Canada | | United Kingdom | | United States | | France | | Germany | | Ireland | | Netherlands | |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
