Epitope open-label extension study to evaluate the long-term clinical benefit and safety of DBV712 in peanut-allergic children (EPOPEX)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dbv Technologies

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

2 Mar 2021 → 14 May 2025

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DBV Technologies S.A

External identifiers

EU CT number

2024-515703-19-00

EudraCT number

2018-003323-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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.

Conditions and MedDRA coding

Peanut allergy

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001481-PIP01-13

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

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.

Exclusion criteria 19

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 antitumor 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 20

1. 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: 1. Proportion of subjects reaching an ED ≥1000 mg peanut protein;
2. Proportion of treatment responders, using the treatment response definition of the EPITOPE study, i.e. a subject is defined as a treatment responder if: - The baseline ED was >10 mg peanut protein and the ED is ≥1000 mg peanut protein at the post-baseline (DBPCFCs) or; -The baseline ED was ≤10 mg and the ED is ≥300 mg peanut protein at the post-baseline DBPCFCs.
3. Proportion of subjects reaching a cumulative dose of at least 1444 mg peanut protein at the post-baseline DBPCFCs;
4. Proportion of subjects reaching a cumulative dose of at least 3444 mg peanut protein at the post-baseline DBPCFCs;
5. 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 postbaseline DBPCFCs;
6. Mean and median CRD of peanut protein;
7. Mean and median ED of peanut protein.
8. The following safety endpoints will be analyzed: 8. Adverse Events and TEAEs by System Organ Class (SOC) and Preferred Term (PT);
9. Treatment-emergent adverse events by maximum severity and by maximum duration and relatedness to the IP;
10. Serious adverse events (SAEs) by SOC and PTs, maximum severity and relatedness to the IP;
11. Treatment-emergent adverse events leading to treatment discontinuation;
12. 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;
13. Incidence, duration and maximum severity of local cutaneous reactions as assessed by the subjects;
14. Incidence and severity of local cutaneous reactions as assessed by the Investigators;
15. Laboratory data, physical examinations and vital signs
16. Spirometry results and peak expiratory flow (PEF) results.
17. The following of study procedure safety criteria will be assessed over 3 years of treatment: 17. Symptoms elicited during the DBPCFCs by severity;
18. Severity of symptoms score during the DBPCFCs;
19. Serious AEs elicited during the DBPCFCs.
20. The safety endpoints will be evaluated in the overall Safety population using the rescheduling rules and by treatment group (VP+VP / Placebo+VP).

Secondary endpoints 7

1. 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: 1. 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);
2. Peanut Skin Prick Test (SPT) average wheal diameters;
3. Description of the quality of life (QoL) questionnaires (Food Allergy Quality of Life Questionnaires [FAQLQ]/ Food 2. Allergy Independent Measure [FAIM]/EQ-5D-5L) data and QoL scores;
4. 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;
5. Epigenetic modifications of the promoters of some specific genes;
6. Sensitization status to other allergens and their evolution over the study period;
7. Scoring atopic dermatitis (SCORAD) index evolution over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dbv Technologies

Sponsor organisation

Dbv Technologies

Address

Batiment Iro, 107 Avenue De La Republique 107 Avenue De La Republique

City

Chatillon

Postcode

92320

Country

France

Scientific contact point

Organisation

Dbv Technologies

Contact name

Pharis Mohideen

Public contact point

Organisation

Dbv Technologies

Contact name

Pharis Mohideen

Third parties 6

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications