E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inherited Epidermolysis Bullosa |
Epidermolyse bulleuse |
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E.1.1.1 | Medical condition in easily understood language |
Illness called Epidermolysis bullosa (EB) that makes skin blister and have open sores and wounds |
Maladie appelée épidermolyse bulleuse (EB) qui produit des cloques sur la peau avec des lésions et des plaies ouvertes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014989 |
E.1.2 | Term | Epidermolysis bullosa |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the double-blind phase is to compare the efficacy of Oleogel-S10 (treatment arm A) with vehicle (treatment arm B) in the promotion of healing of EB partial thickness wounds. This will be assessed as evidenced by the incidence of the first complete closure of the EB target wound (defined as EB partial thickness wound of 10 cm2 to 50 cm2 in size aged ≥21 days in any subtype of inherited EB) within 45±7 days of treatment). |
L’objectif principal de la phase en double aveugle est de comparer l’efficacité d’Oleogel-S10 (bras de traitement A) à celle d’un placebo (bras de traitement B) pour favoriser la cicatrisation des plaies peu profondes de l’épidermolyse bulleuse (EB). Cette efficacité sera évaluée par l’incidence de la première fermeture complète de la plaie cible d’EB (soit une plaie peu profonde d’EB de 10 à 50 cm2 de ≥ 21 jours dans tout sous-type d’EB héréditaire) dans un délai de 45 jours de traitement (±7 jours) |
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E.2.2 | Secondary objectives of the trial |
1/ Compare the efficacy of IMP with placebo as evidenced by several criteria described in the protocol 2/ Compare the safety of IMP with placebo as evidenced by the incidence, severity, and relatedness of AEs and based on laboratory assessments 3/ Compare the tolerability of IMP with placebo 4/ Assess betulin exposure |
1/ Comparer l’efficacité du ME à celle du placebo au vu de différents critères décrits dans le protocole 2/ Comparer la sécurité d’emploi du ME à celle du placebo au vu de l’incidence des événements indésirables (EI), de leur gravité, ainsi que de leur lien avec le traitement et au vu des résultats des analyses biologiques 3/ Comparer la tolérance du ME à celle du placebo 4/ Évaluer l’exposition à la bétuline |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient will be eligible for study participation only if all of the following criteria apply: 1. Male and female patients with any subtype of inherited EB including EBS, JEB, DEB, and Kindler syndrome age ≥4 years [Note: Children <4 years of age may be included only after confirmation by the Independent Data Monitoring Committee (IDMC) upon review of the safety and bioanalytical data at the interim safety review stage]. 2. Patients with an EB target wound (i.e., EB partial thickness wound of 10 cm2 to 50 cm2 in size aged ≥21 days) 3. Patient and/or his/her legal representative has/have been informed, has/have read and understood the patient information/informed consent form, and has/have given written informed consent 4. Patient and/or his/her legal representative must be able and willing to follow study procedures and instructions |
Un patient ne pourra participer à cette étude que si tous les critères suivants sont satisfaits : 1. Garçon ou fille ≥ 4 ans présentant une EB héréditaire, quel qu'en soit le sous-type : EBS, EBJ, EBD ou syndrome de Kindler [Remarque : les enfants de moins de quatre ans pourront participer à l’étude uniquement après confirmation du comité indépendant de surveillance après examen des données de sécurité d’emploi et bioanalytiques lors de l’évaluation intermédiaire de la sécurité.] 2. Patient présentant une plaie cible d’EB (à savoir une plaie peu profonde d’EB de 10 à 50 cm2 de ≥ 21 jours) 3. Patient et/ou représentant légal du patient informé, ayant lu et compris la note d’information au patient et le formulaire de consentement éclairé, et ayant donné son consentement éclairé par écrit 4. Patient et/ou représentant légal du patient capable et désireux de suivre les procédures et les instructions de l’étude |
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E.4 | Principal exclusion criteria |
A patient will not be eligible to participate in this study if any of the following criteria apply: 1. EB target wound with clinical signs of local infection 2. Use of systemic antibiotics for wound-related infections within 7 days prior to enrolment 3. Administration of systemic or topical steroids (except for inhaled, ophthalmic or topical applications, such as budesonide suspension for oesophageal strictures [e.g., Pulmicort respules® 0.25 mg/2 mL or 0.5 mg/2 mL]) within 30 days before enrolment 4. Immunosuppressive therapy or cytotoxic chemotherapy within 60 days prior to enrolment 5. Patient has undergone stem cell transplant or gene therapy for the treatment of inherited EB 6. Current and/or former malignancy including basal cell carcinomas and squamous cell carcinomas 7. Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry 8. Factors present in the patient and/or his/her legal representative that could interfere with study compliance such as inability to attend scheduled study visits or compliance with home dressing changes 9. Pregnant or nursing women and women of childbearing potential including postmenarchal female adolescents not willing to use an effective form of birth control with failure rates <1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine contraceptive device, sexual abstinence, vasectomised partner) during participation in the study (and at least 3 months thereafter) 10.Patient is a member of the investigational team or his/her immediate family 11.Patient lives in the same household as a study participant. |
Les patients qui répondent à un ou plusieurs des critères suivants ne pourront pas participer à cette étude : 1. Plaie cible d’EB présentant des signes cliniques d’infection locale 2. Prise d’antibiotiques systémiques pour des infections associées aux plaies au cours des sept jours précédant l’inclusion dans l’étude 3. Administration de corticoïdes systémiques ou topiques (sauf par inhalation, voie ophtalmique ou topique, comme le budésonide en suspension pour les rétrécissements de l’Å“sophage [p. ex., Pulmicort respules® 0,25 mg/2 ml ou 0,5 mg/2 ml]) au cours des 30 jours précédant l'inclusion 4. Traitement immunosuppresseur ou chimiothérapie cytotoxique au cours des soixante jours précédant l’inclusion dans l’étude 5. Patient ayant subi une greffe de cellules souches ou une thérapie génique pour traiter l’EB héréditaire 6. Tumeur maligne actuelle et/ou antérieure, dont les carcinomes basocellulaires et les carcinomes épidermoïdes 7. Participation à une étude interventionnelle ou traitement par un médicament en phase d’expérimentation pour une quelconque maladie au cours des quatre semaines précédant l’inclusion dans l’étude 8. Facteurs propres au patient ou à son représentant légal susceptibles d’avoir une incidence sur la conformité de l’étude, comme par exemple l’incapacité à se présenter aux visites programmées de l’étude ou un problème d’observance concernant les changements de pansements à domicile 9. Femmes enceintes ou qui allaitent et femmes en âge de procréer, y compris les adolescentes menstruées, qui refusent d’utiliser un moyen de contraception efficace affichant des taux d’échec < 1 % par an (p. ex., implant, contraceptif injectable ou oral combiné, dispositif intra-utérin, abstinence sexuelle, vasectomie du partenaire) pendant leur participation à l’étude (et pendant au moins trois mois par la suite) 10. Patient ou membre de la famille du patient appartenant à l’équipe de recherche 11. Patient résidant à la même adresse qu’un autre participant de l’étude. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with first complete closure of the EB target wound (defined as EB partial thickness wound of 10 cm2 to 50 cm2 in size aged ≥21 days in any subtype of inherited EB) within 45±7 days of treatment with Oleogel-S10 compared to vehicle based on clinical assessment by the investigator (the wound will be rated as “closed” at first appearance of complete reepithelialisation without drainage confirmed by a second observation within the following week) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints • Time to first complete closure of the EB target wound as evidenced by clinical assessment until D90±7. • Proportion of patients with first complete closure of the EB target wound within D14±5, D30±7, D60±7, and D90±7 based on clinical assessment by the investigator • Proportion of patients with first complete closure of the EB target wound within at D7±5, D14±5, D30±7, D45±7, D60±7, and D90±7 based on patient assessment • Proportion of patients with first complete closure of the EB target wound at D7±5, D14±5, D30±7, D45±7, D60±7, and D90±7 based on blinded evaluation of photographs • Percentage change from baseline (D0) in EB target wound size as evidenced by blinded evaluation of photographs taken at D7±5, D14±5, D30±7, D45±7, D60±7, and D90±7 • Change from baseline (D0) in total body wound burden as evidenced by clinical assessment using Section I (assessment of the skin except for the anogenital region) of the ‘EB Disease Activity and Scarring Index’ (EBDASI) at D30±7, D60±7, and D90±7 • Change from baseline (D0) in body surface area percentage (BSAP) of TBSA affected by EB partial thickness wounds as evidenced by clinical assessment based on the ‘Lund and Browder’ chart at D30±7, D60±7, and D90±7 • The incidence and maximum severity of wound infection between baseline (D0) and D90±7 as evidenced by AEs and/or use of topical and/or systemic antibiotics (related to wound infection) • Change from baseline (D0) in ‘background’ pain using the ‘Face, Legs, Activity, Cry, Consolability’ (FLACC) scale in patients <4 years of age and the ‘Wong-Baker FACES® Pain Rating Scale’ in patients ≥4 years of age before wound dressing changes at D7±5, D14±5, D30±7, D45±7, D60±7, and D90±7 • Change from baseline (D0) in ‘procedural’ pain using the FLACC scale in patients <4 years of age and the ‘Wong-Baker FACES® Pain Rating Scale’ in patients ≥4 years of age after wound dressing changes at D7±5, D14±5, D30±7, D45±7, D60±7, and D90±7 Change from baseline (D0) in itching using the ‘Itch Man Scale’ in patients ≥4 years and up to 13 years of age and the ‘Leuven Itch Scale’ in patients ≥14 years of age before wound dressing changes at D7±5, D30±7, D60±7, and D90±7 • Change from baseline in impact of wounds on sleep (in patients ≥14 years of age) as measured by differences in 11-point Likert scales at D7±5, D30±7, D60±7, and D90±7 • The number of days missed from school or from work due to EB as reported by patients at D0, D14±5, D30±7, D45±7, D60±7, and D90±7 • Evaluation of the treatment response (in patients ≥14 years of age) using the Treatment Satisfaction Questionnaire for Medication (TSQM), Version 9 at D7±5, D30±7, D60±7, and D90±7 Safety endpoints • Incidence, severity, and relatedness of AEs • Local tolerability as judged by the investigator • Safety laboratory data • Systemic exposure to betulin, if consent provided |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 20 |
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 |
Israel |
Mexico |
United States |
Austria |
France |
Spain |
Switzerland |
Germany |
Greece |
Italy |
Croatia |
Ireland |
Turkey |
United Kingdom |
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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
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LVLS estimated in January 2021 |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |