E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ornithine transcarbamylase deficiency |
Deficiencia de ornitina transcarbamilasa |
|
E.1.1.1 | Medical condition in easily understood language |
Inherited disorder causing accumulation of ammonia |
Transtorno hereditario que da lugar a la acumulación de amoniaco |
|
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 | 10071107 |
E.1.2 | Term | Ornithine transcarbamylase deficiency |
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 determine the long-term safety of DTX301 following a single IV dose in adults with late-onset OTC deficiency. |
Determinar la seguridad a largo plazo de DTX301 después de una sola dosis intravenosa (IV) en adultos con deficiencia de OTC de comienzo tardío. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of DTX301 on AUC0-24 for plasma ammonia following a single IV dose in adults with late-onset OTC deficiency.
To evaluate the long-term effects of DTX301 on the rate of ureagenesis in adults with late-onset OTC deficiency. |
Evaluar la eficacia a largo plazo de DTX301 en AUC0-24 para el amoníaco plasmático después de una sola dosis IV en adultos con deficiencia de OTC de comienzo tardío.
Evaluar los efectos a largo plazo de DTX301 en la tasa de ureagénesis en adultos con deficiencia de OTC de comienzo tardío. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed the Week 52 visit in Study 301OTC01. Note that the Day 0 visit of Study 301OTC02 may coincide with the Week 52 visit of Study 301OTC01. 2. Willing and able to provide written informed consent. 3. Willing, able, and committed to comply with scheduled study site visits, study procedures, and requirements. |
1. Haber completado la visita de la semana 52 en el estudio 301OTC01. Hay que advertir de que la visita del día 0 del estudio 301OTC02 podría coincidir con la visita de la semana 52 del estudio 301OTC01. 2. Disposición y capacidad para otorgar el consentimiento informado por escrito. 3. Disposición, capacidad y compromiso para cumplir las visitas programadas al centro del estudio y los procedimientos y requisitos del estudio. |
|
E.4 | Principal exclusion criteria |
1. Planned or current participation in another interventional clinical study that may confound the efficacy or safety evaluation of DTX301 during the duration of this study. 2. Any clinically significant medical condition that, in the opinion of the investigator, would pose a risk to subject safety or would impede the study. |
1. Participación prevista o actual en cualquier otro estudio clínico intervencionista que pueda confundir la evaluación de la eficacia o la seguridad de DTX301 durante este estudio. 2. Cualquier enfermedad clínicamente importante que, en opinión del investigador, suponga un riesgo para la seguridad del sujeto o impida el estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of AEs and SAEs for each dosing cohort assessed by severity and relationship to study product. |
Incidencia de AA y AAG por cada cohorte de dosis, evaluados según la intensidad y la relación con el fármaco del estudio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the time the subject signs the Informed Consent Form through the end of study/early withdrawal visit. |
Desde la firma del Consentimiento Informado por el sujeto hasta el final del estudio/visita de retirada prematura. |
|
E.5.2 | Secondary end point(s) |
The change from baseline (Day 0 of Study 301OTC01) in AUC0-24 for plasma ammonia over time to 260 weeks following IV administration of DTX301.
The change from baseline (average of Screening and Day 1 results of Study 301OTC01) in the rate of ureagenesis (as measured by the generation of [13C]urea over 4 hours) as determined by gas chromatography mass spectrometry over time to 260 weeks following IV administration of DTX301. |
Variación con respecto al momento basal (día 0 del estudio 301OTC01) del AUC0-24 para el amoníaco plasmático a lo largo del tiempo hasta 260 semanas después de la administración IV de DTX301.
Variación con respecto al momento basal (promedio de los resultados en la selección y el día 1 del estudio 301OTC01) de la tasa de ureagénesis (medida mediante la generación de [13C]urea durante 4 horas) según lo determinado por la espectrometría de masas-cromatografía de gases a lo largo del tiempo hasta 260 semanas después de la administración IV de DTX301. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Plasma ammonia: Day 0, Week 52, Week 104, Week 156, Week 208
Ureagenesis: Day 0, Week 26, Week 52, Week 78, Week 104, Week 130, Week 156, Week 182, Week 208 |
Amoniaco plásmatico: Dia 0, Semana 52, Semana 104, Semana 156, Semana 208
Ureagénesis: Dia 0, Semana 26, Semana 52, Semana 78, Semana 104, Semana 130, Semana 156, Semana 182, Semana 208. |
|
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 | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Long-term follow-up study |
Estudio de seguimiento a largo plazo |
|
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 | No |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Canada |
Spain |
United Kingdom |
United States |
|
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
|
LVLS |
Ultima visita del ultimo sujeto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |