| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 100000004870 |
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| 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 objective of this study is to verify the safety and local tolerance of the 2 DBV712 doses of 100 and 250 μg and to assess the efficacy and safety of DBV712 to induce desensitization to peanut in peanut-allergic subjects 1 to 3 years of age after a 12-month treatment period by EPIT. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female from 1-3 years of age at Visit 1.
2. Physician-diagnosed peanut allergy or high suspicion of peanut allergy as assessed by the physician: child presenting signs, symptoms and a medical and/or a family history putting him/her at high risk of having a peanut allergy and/or history of presence of peanut-specific IgE and/or positive SPT.
3. Subject currently following a strict peanut-free diet.
4.Signed informed consent of parent(s)/guardian(s) of the children aged 1-3 years.
5. Peanut-specific immunoglobulin E (IgE) level (ImmunoCAP system) > 0.7 kU/L.
6. Positive peanut SPT with a largest wheal diameter ≥ 6 mm.
7. Positive DBPCFC to peanut, with symptoms meeting the challenge stopping criteria at an Eliciting Dose (ED) ≤300 mg peanut protein.
8. Parents/guardians and subjects willing to comply with all study requirements during their participation in the study. |
|
| E.4 | Principal exclusion criteria |
1. Peanut allergic subjects presenting a medical history of severe anaphylaxis to peanut will be excluded for this study. Severe anaphylaxis is defined by the Grade 3 of the Anaphylaxis Staging System (Appendix 4), including:
•Severe hypoxia, persistent hypotension or more than 20% drop in blood pressure, neurological compromise, or
•Cyanosis or SpO2 ≤ 92% at any stage, confusion, cardiovascular collapse, loss of consciousness, bradychardia, cardiac arrest.
2. Severe reaction during the entry/screening DBPCFC, defined as any of the following:
•Need for intubation
•Hypotension persisting after epinephrine administration
•Need for three doses or more of systemic epinephrine.
3. Subject with reactions to the placebo formula during the screening DBPCFC (with reactions deemed to stopping the challenge).
4. Subjects who fail to complete the entry food challenge due to any reason including clear aversion to the food formula matrix,
5. Subject with any clinically significant abnormality identified at the time of screening such as major infantile infectious diseases (pox, measles) which in the judgment of the Investigator can preclude safe participation or strict compliance to the protocol procedures. Subjects can be considered for the study after recovery from these diseases.
6. Viral upper respiratory infection or gastroenteritis or any severe disease within 7 days of food challenge (challenge must be rescheduled at least after 7 days upon recovery).
7. Hypersensitivity to any of the Viaskin® patch components (except to peanut protein), including the adhesive film.
8. Hypersensitivity to any component of the food challenge formula (except to peanut protein) or a known history of apple allergy.
9. Inability to discontinue short-acting antihistamines or long-acting antihistamines for the minimum wash-out periods required (depending on half-lives and specified in APPENDIX 3) prior to the skin prick testing or the food challenges.
10. Diagnosis of asthma that fulfills any of the following criteria:
•Uncontrolled asthma (as per Global Initiative for Asthma [GINA] latest guidelines; see APPENDIX 8)
•Asthma requiring controller treatment step 3 or higher (as per GINA latest guidelines: either moderate [double low dose] of inhaled corticosteroid, or association of inhaled corticosteroid with leukotriene receptor antagonist [see APPENDIX 8]. Long acting beta agonists are not recommended below 5 years)
•History of 2 or more systemic corticoid courses within the 3 previous months prior to Visit 1 or 1 systemic corticoid course within the 4 weeks prior to Visit 1 for treating a diagnosed asthma.
•Prior intubation/mechanical ventilation for asthma within one year prior to Visit 1.
Asthmatic subjects with the following treatment options are eligible:
−No controller treatment (GINA Step 1),
−Controller treatment monotherapy (GINA Step 2):
o with daily or short-term course (intermittent) low dose inhaled corticosteroid,
o or with leukotriene receptor antagonist.
11. 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 latest guidelines, see APPENDIX 8).
12. Generalized dermatologic disease (e.g. severe atopic dermatitis, uncontrolled generalized eczema, ichthyosis vulgaris) extending widely on the skin and especially on the back with no intact zones to apply the Viaskin® patches.
13. Diagnosis of mast cell disorders including mastocytosis or urticaria pigmentosa as well as hereditary or idiopathic angioedema;
14. Prior history of any immunotherapy to any food (e.g. oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction). Subjects who received a prior oral immunotherapy of less than 1 month-duration which ended at least 3 months before Visit 1 are eligible for inclusion.
15. Subject receiving or planning to receive any immunotherapy (aeroallergens, venoms, anti-infective…) during their participation in the study. These immunotherapies must be discontinued at the time of Visit 1.
16. Symptomatic seasonal allergies that may interfere with the conduct of a DBPCFC. These subjects could be screened at a time when such allergies are asymptomatic (for example outside of the culprit season);
17. Subject receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
18. Subject who received anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab), any biologic immunomodulatory therapy, cyclosporine or other immunosuppressive drugs within one year prior to Visit 1 or during screening period. Topical calcineurin inhibitors are permitted.
For complete list: refer to protocol |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the difference between the percentage of treatment responders at Month 12 in the active selected DBV712 group (250µg) compared to the placebo group in the overall population. A subject is defined as a treatment responder if:
• The initial Eliciting Dose (ED) was >10 mg peanut protein and the ED is ≥1,000 mg peanut protein at the post-treatment DBPCFC at Month 12; or
• The initial ED was ≤10 mg peanut protein and the ED is ≥300 mg peanut protein at the post-treatment DBPCFC at Month 12. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Refer to Section 6.1 of the protocol. |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline to Month 12 in Cumulative Reactive Dose (CRD) in the selected active DBV712 group (250µg) versus the placebo group;
• Change from baseline to Month 12 in ED in the selected active DBV712 group (250µg) versus the placebo group; |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Refer to Section 6.1 of the protocol. |
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| 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 | 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 | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 States |
| France |
| Germany |
| Ireland |
| Netherlands |
| United Kingdom |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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