E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
X-linked hypohidrotic ectodermal dysplasia (XLHED) |
Displasia ectodérmica hipohidrótica ligada al cromosoma X (DEHLX) |
|
E.1.1.1 | Medical condition in easily understood language |
X-linked hypohidrotic ectodermal dysplasia (XLHED) |
Displasia ectodérmica hipohidrótica ligada al cromosoma X (DEHLX) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072592 |
E.1.2 | Term | Hypohidrotic ectodermal dysplasia |
E.1.2 | System Organ Class | 100000004850 |
|
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 assess the efficacy of intra-amniotic administrations of ER004 on sweating ability in male XLHED subjects with a null mutation in EDA at 6 months of age, compared to untreated matched control subjects. |
Evaluar la eficacia de la administración intraamniótica de ER004 sobre la capacidad de sudoración en varones con DEHLX con una mutación anuladora en EDA a la edad de 6 meses, en comparación con sujetos testigo compatibles no tratados. |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of intra-amniotic administrations of ER004 on sweat pore density and dentition in male subjects with XLHED at 6 months of age To assess the efficacy of intra-amniotic administrations of ER004 in male subjects with XLHED up to 5 years of age To assess the safety and tolerability of intra-amniotic administrations of ER004 in male subjects with XLHED up to 6 months of age and in mothers up to 1 month after delivery To assess the long-term safety of intra amniotic administrations of ER004 in male subjects with XLHED up to 5 years of age To assess safety parameters in untreated relatives (controls) |
Evaluar la eficacia de la administración intraamniótica de ER004 en la densidad de poros sudoríparos y en la dentadura en varones con DEHLX a la edad de 6 meses Evaluar la eficacia de la administración intraamniótica de ER004 en varones con DEHLX hasta la edad de 5 años Evaluar la seguridad y tolerabilidad de la administración intraamniótica de ER004 en varones con DEHLX hasta la edad de 6 meses y en las madres hasta 1 mes después del parto Evaluar la seguridad a largo plazo de la administración intraamniótica de ER004 en varones con hasta la edad de 5 años Evaluar los parámetros de seguridad en familiares no tratados (testigos) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For mother : Adult mother with confirmed pregnancy no later than week 23+6 and genetically confirmed as carrier of an EDA mutation
For fetus subject: Male Fetal subject with confirmed diagnosis of XLHED
Untreated relative : Untreated male relative subject ages between 6 months and 60 years with the same EDA mutation as the treated subject |
Para la madre: Madre adulta con embarazo confirmado como máximo en la semana 23+6 y portadora de una mutación en EDA confirmada mediante prueba genética Para el sujeto fetal: Feto masculino con diagnóstico confirmado de DEHLX Familiar no tratado: familiar cercano no tratado con edades comprendidas entre los 6 meses y los 60 años con la misma mutación EDA que el sujeto tratado |
|
E.4 | Principal exclusion criteria |
For mother: Any evidence of active maternal infection associated with a risk of preterm birth and/or congenital anomalies of prenatal and postnatal risk to the child Documented maternal HIV infection. Any pre-existing maternal medical condition that increases the risk of preterm birth or increases the risk of a serious untoward event occurring to the mother during pregnancy. Any pregnancy disorder associated with an increased risk of preterm birth, and/or maternal, fetal or neonatal morbidity/mortality
For fetal subject 1.Second major anatomic anomaly (not related to the underlying XLHED) that contributes to a significant morbidity or mortality risk, or echocardiogram or ultrasonography or other findings that indicate a high risk of fetal demise or risk of preterm birth. 2.Any condition other than XLHED (i.e., other forms of ectodermal dysplasia, large orofacial clefts) that is likely to have an impact on the number of tooth germs. 3.Any other medical condition which in the opinion of the investigator would not allow for safe conduct of the study for the subject, or that would interfere with efficacy assessments (e.g., any disorders that lead to reduced fetal swallowing).
Untreated Relative 1.Carrier of an hypomorphic EDA mutation. 2.Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists. 3.Presence of an implanted device (e.g., defibrillator, neurostimulator, pacemaker). 4.Previous treatment with the study intervention by any route of administration prior to study start. |
Para la madre: Cualquier prueba de infección materna activa asociada con un riesgo de parto prematuro o anomalías congénitas con riesgo prenatal y posnatal para el bebé. Infección por VIH materna confirmada. Cualquier enfermedad anterior de la madre que aumente el riesgo de parto prematuro o de que esta sufra un acontecimiento adverso grave durante el embarazo. Cualquier trastorno del embarazo asociado con un aumento del riesgo de parto prematuro o morbilidad/mortalidad materna, fetal o neonatal
Para el sujeto fetal 1.Otra anomalía anatómica de importancia (no secundaria a DEHLX) que contribuya a un riesgo notable de morbilidad o mortalidad, o un ecocardiograma o ecografía u otros hallazgos que indiquen un elevado riesgo de muerte fetal o riesgo de parto prematuro. 2.Cualquier enfermedad aparte de DEHLX (p. ej., otras formas de displasia ectodérmica, labio leporino con fisura grande) que puedan influir en la cantidad de gérmenes dentales. 3.Cualquier otra enfermedad que, en opinión del investigador, no permitiera la realización segura del estudio para el sujeto, o que pudiera interferir con la evaluación de la eficacia (p. ej., cualquier desorden que reduzca el tránsito fetal).
Familiar no tratado 1.Portador de una mutación hipomórfica en EDA. 2.Hipersensibilidad conocida a la pilocarpina o a los agonistas muscarínicos similares a la pilocarpina. 3. Presencia de un dispositivo implantado (p. ej., desfibrilador, neuroestimulador, marcapasos). 4.Tratamiento previo con la intervención del estudio por cualquier vía de administración antes del inicio del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean sweat volume collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating). |
Volumen medio de sudor recogido en ambos antebrazos después de la estimulación local con pilocarpina (sudoración provocada por pilocarpina). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For treated subject, mean sweat volume is collected at 6 months of age (V8) (corrected age for subjects born at < 37 weeks) |
Para el sujeto tratado, la media del volumen de sudor se recoge a los 6 meses de edad (V8) (edad corregida para los sujetos que nazcan con < 37 semanas) |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoints: •Mean sweat pore density (number/cm2) determined by direct visualization with a VivaScope® at 6 months of age (V8) at 2 different sites on the soles of the feet •Dental development evaluated by the number of erupted teeth and tooth buds (palpable alveolar structures in the alveolar ridge) as determined by oral examination at 6 months of age (V8)
Other secondary endpoints: •Mean sweat volume on both forearms measured from a pilocarpine-induced sweat test (at other timepoints than 6 months). •Sweat pore density (at other timepoints than 6 months). •Dentition (at other timepoints than 6 months). •Dry eye •Salivation assessment •Number of XLHED related hospitalizations •Assessment of eczema •Safety and tolerability assessments •Health-related quality of life assessments |
Criterios de valoración secundarios clave: •Densidad media de poros sudoríparos (número/cm2) determinada por visualización directa con VivaScope® a la edad de 6 meses (V8) en dos áreas diferentes en la zona plantar •Desarrollo dental evaluado por el número de dientes emergentes y brotes dentarios (estructuras alveolares palpables en el borde alveolar) determinado durante la exploración bucal a la edad de 6 meses (V8)
Otros criterios de valoración secundarios: •Volumen medio de sudor en ambos antebrazos, medido durante una prueba de sudor provocada por pilocarpina (en momentos no correspondientes a los 6 meses). •Densidad de poros sudoríparos (en otros momentos no correspondientes a los 6 meses). •Xeroftalmia •Evaluación de la salivación •Número de hospitalizaciones relacionadas con la DEHLX •Evaluación de eccemas •Evaluaciones de la seguridad y la tolerabilidad •Evaluaciones de la calidad de vida relacionada con la salud |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 6 month of age for primary and key secondary endpoints |
A los 6 meses de edad para los criterios de valoración principal y secundarios clave |
|
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 | No |
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) | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Genotype-matched controlled |
|
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 | 5 |
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 |
United States |
United Kingdom |
|
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
|
The End of study is defined as the time point when the last treated subject has completed the last visit (V14) or the premature withdrawal visit. |
El final del estudio se define como el momento en que el último sujeto tratado haya completado la última visita (V14) o la visita de retirada anticipada. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |