E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recessive Dystrophic Epidermolysis Bullosa (RDEB) due to mutation(s) in exon 73 of the COL7A1 gene |
Epidermólisis ampollosa distrófica recesiva (EADR) debido a una mutación o mutaciones en el exón 73 del gen COL7A1 |
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E.1.1.1 | Medical condition in easily understood language |
RDEB due to mutation(s) in exon 73 of the COL7A1 gene |
EADR debido a una mutación o mutaciones en el exón 73 del gen COL7A1 |
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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 |
- To evaluate safety and tolerability following topical administration of QR-313 to the target wound area (TWA) - To assess the effect of QR-313 on the exclusion (skipping) of exon 73 from COL7A1 mRNA |
- Evaluar la seguridad y la tolerabilidad tras la aplicación tópica de QR-313 en el área de herida diana (AHD) - Evaluar el efecto de QR-313 en la exclusión (salto) del exón 73 del ARNm del gen COL7A1 |
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E.2.2 | Secondary objectives of the trial |
- To assess the preliminary efficacy on wound healing and skin strength - To assess systemic exposure after topical administration of QR-313 to the Target Wound Area (TWA) - To assess the effect of QR-313 on the presence of collagen type VII protein and anchoring fibrils |
- Evaluar la eficacia preliminar en la curación de la herida y en la resistencia de la piel - Evaluar la exposición sistémica tras la administración tópica de QR-313 en el área de herida diana (AHD) - Evaluar el efecto de QR-313 en la presencia de la proteína del colágeno de tipo VII y de las fibrillas de anclaje |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, ≥ 2 years of age at Screening with a clinical diagnosis of RDEB with confirmation of at least one of the alleles of the COL7A1 gene containing one or more pathogenic mutations in exon 73. 2. Have at least one TWA of 10 x 10 cm that shows dynamic wound healing, no signs of local infection and in which a wound can be selected with the following criteria: a. a surface area ranging from 5 to 60 cm2 b. open wound that has healing potential c. exposed sub-epidermal tissue to allow absorption of the IMP d. no suspicion of current squamous cell carcinoma (SCC) upon visual inspection |
1. Sujetos de ambos sexos, ≥2 años de edad en el momento de la selección con un diagnóstico clínico de EADR con confirmación de una o más mutaciones patogénicas en el exón 73 en al menos uno de los alelos del gen COL7A1. 2. Tener al menos un AHD de 10 x 10 cm que muestre curación dinámica de la herida, sin signos de infección local y en la que se pueda seleccionar una herida que cumpla los criterios siguientes: a. área de superficie de 5 a 60 cm2 b. herida abierta con potencial de curación c. tejido subepidérmico expuesto para permitir la absorción del PEI d. sin sospecha en el momento de la inspección visual de carcinoma escamocelular (CEC) simultáneo. |
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E.4 | Principal exclusion criteria |
1. Pregnant or breast-feeding female 2. Hemoglobin level at Screening requiring transfusion. The subject may be rescreened when the condition is considered stable 3. Untreated carcinoma of the TWA or history of carcinoma within 5 years prior to Screening, except adequately treated cutaneous squamous or basal cell carcinoma. 4. Life expectancy less than 6 months, as assessed by the Investigator 5. Current or known history of clinically significant hepatic or renal disease, that in the opinion of the Investigator, could impact subject safety or study participation. 6. Treatment with any systemic immunomodulators, immunosuppressants or cytotoxic chemotherapy within 2 months prior to the Baseline visit. |
1. Mujeres embarazadas o en periodo de lactancia 2. Nivel de hemoglobina en la selección que requiere transfusiones. El sujeto puede volverse a someter al procedimiento de selección cuando la afección se considere estable. 3. Carcinoma sin tratar en el AHD o antecedentes de carcinoma en los 5 años anteriores a la selección, a excepción del carcinoma escamocelular o basocelular cutáneo adecuadamente tratado. 4. Esperanza de vida inferior a 6 meses, según la evaluación del investigador. 5. Presencia actual o antecedentes conocidos de enfermedad hepática o renal clínicamente significativa que, en opinión del investigador, pueda afectar a la seguridad del sujeto o a la participación en el estudio. 6. Tratamiento sistémico con un inmunomodulador, inmunosupresor o quimioterapia citotóxica en los 2 meses anteriores a la visita basal. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Assessment of adverse events/serious adverse events - Absence of exon 73 in COL7A1 mRNA, detected by polymerase chain reaction (PCR) |
- Evaluación de los acontecimientos adversos/acontecimientos adversos graves - Ausencia del exón 73 en el ARNm del gen COL7A1, detectada mediante la reacción en cadena de la polimerasa (RCP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AEs are assessed throughout the study - Exon skip is assessed after 1 week of treatment with IMP |
- Los AAs son evaluados a lo largo del estudio - El salto del exón se evalúa después de 1 semana de tratamiento con el PEI |
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E.5.2 | Secondary end point(s) |
- Wound size (surface area) - Wound severity as assessed by Physician Subjective Assessment of Severity (PSAS) and Physician Subjective Assessment of Change (PSAC) - Wound status as assessed by Short Wound Specific Questionnaire (SWSQ) - Status of wound closure - Onset of (re)blistering of a healed wound - Serum levels of QR-313 - Presence of collagen type VII protein expression, measured by indirect immunofluorescence (IIF) microscopy - Presence of anchoring fibrils measured by transmission electron microscopy (TEM) |
- Tamaño de la herida (área de superficie) - Gravedad de la herida evaluada mediante la escala de valoración subjetiva de la gravedad por parte del médico (Physician Subjective Assessment of Severity, PSAS) y la escala de valoración subjetiva del cambio por parte del médico (Physician Subjective Assessment of Change, PSAC) - Estado de las heridas evaluado mediante un cuestionario breve específico de lesiones (Short Wound Specific Questionnaire, SWSQ) - Estado de la cicatrización de las heridas - Aparición de (nuevas) ampollas en una herida curada - Niveles séricos de QR-313 - Presencia de expresión de la proteína del colágeno de tipo VII, determinada mediante microscopía de inmunofluorescencia indirecta (IFI) - Presencia de fibrillas de anclaje determinada mediante microscopía electrónica de transmisión (MET) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- weekly images are taken throughout the study for the purpose of the wound healing and skin strength parameters - serum level of QR-313 is measured after 1 week of treatment with IMP - collagen type VII protein expression at 8 weeks after last dose of IMP (EOS) - anchoring fibrils measured at 8 weeks after last dose of IMP (EOS) |
- se harán fotografías semanales a lo largo del estudio con el propósito de los parámetros de curación de la herida y la resistencia de la piel - se miden los niveles séricos de QR-313 después de 1 semana de tratamiento con el PEI - la expresión de la proteína del colágeno de tipo VII a las 8 semanas después de la última dosis de PEI (FdE) - medida de las fibrillas de anclaje a las 8 semanas después de la última dosis de PEI (FdE) |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 8 |
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 |
Austria |
Canada |
Czech Republic |
France |
Germany |
Spain |
United Kingdom |
United States |
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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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |