E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Intestinal Malabsorption in Preterm Infants. | Malabsorción intestinal en recién nacidos prematuros. | |
E.1.1.1 | Medical condition in easily understood language | Digestive tract (oesophagus, stomach and intestines)in preterm infants is not fully developed. These infants are unable to absorb sufficient nutrients, which is described as intestinal malabsorption. | El tracto digestivo (esófago, estómago e intestinos) de los bebés prematuros no está completamente desarrollado y no pueden absorber suficientes nutrientes, lo que se llama malabsorción intestinal. | |
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 | 10032413 | E.1.2 | Term | Other preterm infants, 750-999 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032407 | E.1.2 | Term | Other preterm infants, 1,250-1,499 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032409 | E.1.2 | Term | Other preterm infants, 1,750-1,999 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032411 | E.1.2 | Term | Other preterm infants, 2,500+ grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032415 | E.1.2 | Term | Other preterm infants, unspecified {weight} | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032412 | E.1.2 | Term | Other preterm infants, 500-749 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032406 | E.1.2 | Term | Other preterm infants, 1,000-1,249 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032408 | E.1.2 | Term | Other preterm infants, 1,500-1,749 grams | E.1.2 | System Organ Class | 100000004868 | |
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 | 10032410 | E.1.2 | Term | Other preterm infants, 2,000-2,499 grams | E.1.2 | System Organ Class | 100000004868 | |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | To assess the efficacy of ELGN-2112 as compared to placebo on intestinal malabsorption in preterm infants as measured by the time to full enteral feeding. | Evaluar la eficacia del tratamiento con ELGN-2112 en comparación con placebo sobre la malabsorción intestinal en lactantes prematuros, medida por el tiempo hasta la nutrición enteral completa. | |
E.2.2 | Secondary objectives of the trial | 1To assess effect of ELGN-2112 compared to placebo on number of days until full wean off PN, 2To assess the effect of ELGN-2112 compared to placebo on nº of days to discharge to home, 3Incidence and severity of Necrotizing Enterocolitis (NEC) in infants born at 26-28 weeks GA, 4Percentage of infants reaching full enteral feeding within 6, 8, and 10 days from initiation of treatment, 5Number of days to 120 ml/kg/day for three consecutive days, 6Number of days until PN wean off (time to amino acids and lipids withdrawal), 7Percentage of infants weaned off PN within 4, 6, and 8 days from initiation of treatment, 8Percent enteral/ parenteral feedings from total nutrition over time, 9Number of days to discharge from primary hospital, 10Anthropometrics, 11Percent of infants with culture proven nosocomial sepsis, 12Percent of infants experiencing one of the adverse events of relevance (NEC, Infections, Death), 13Retinopathy of prematurity (ROP) activity score at 30-36 weeks PMA. | 1Evaluar el efecto de ELGN-2112 en comparación con placebo en el nº de días hasta el abandono completo de la NP, 2Efecto de ELGN-2112 en comparación con placebo sobre el nºde días hasta el alta hospitalaria, 3Incidencia y gravedad de la enterocolitis necrosante en lactantes nacidos a las 26-28 semanas de EG, 4% de lactantes que alcanzaran la nutrición enteral completa en los 6, 8 y 10 días siguientes al inicio del tratamiento, 5Nº de días hasta 120 ml/kg/día durante 3 días consecutivos, 6Nº de días hasta el abandono de la NP, 7% de lactantes que dejaron de recibir NP en los 4, 6 y 8 días siguientes al inicio del tratamiento, 8Porcentaje de tomas respecto a la nutrición total a lo largo del tiempo, 9Número de días hasta el alta, 10Antropometría, 11Porcentaje de lactantes con sepsis nosocomial confirmada por cultivo, 12Porcentaje de lactantes que sufrieron uno de los acontecimientos adversos de interés, 13Puntuación de actividad de la retinopatía del prematuro a las 30-36 semanas de EPM. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1. Male or female pre-term infants 26 and up to 32 weeks gestation (32 weeks + 0 day maximum). Gestational age matching (±2 weeks) between maternal dates and/or early antenatal ultrasound*. 2. Birth weight ≥ 500g. 3. Singleton, or twin birth. 4. Postnatal age up through and including Day 5 (up to 120 hours post birth). 5. Fraction of inspired oxygen ≤ 0.60 at enrolment. 6. Infants must demonstrate cardiovascular stability at time of enrolment and would be considered unstable if they require blood pressure support via a central line. 7. Infant is able to tolerate enteral feed. 8. Infant is expected to wean off PN at the primary hospital. 9. Informed consent form (ICF) signed by parents or legal guardian. 10. In the Investigator’s opinion, the infant is able to comply with the study procedures and sufficiently stable to partake in the trial to completion. * If both exist and difference > 2 weeks, based on early antenatal ultrasound | 1.Lactantes prematuros de ambos sexos de 26 a 32 semanas de gestación (32 semanas + 0 días como máximo). Emparejamiento de la edad de gestación (±2 semanas) entre las fechas maternas y la ecografía prenatal precoz*. 2.Peso al nacer ≥500 g. 3.Parto único o gemelar. 4.Edad posnatal hasta el día 5 inclusive (hasta 120 horas después del parto). 5.Fracción de oxígeno inspirado ≤0,60 en la inclusión. 6.Los lactantes deben mostrar estabilidad cardiovascular en el momento del reclutamiento en el estudio y se les considerará inestables si precisan apoyo de la presión arterial a través de una vía central. 7.El lactante tolera la alimentación enteral. 8.Se espera que el lactante deje de recibir la nutrición parenteral (NP) en el hospital principal. 9.Documento de consentimiento informado firmado por los padres o el tutor legal. 10.En opinión del investigador, el lactante es capaz de cumplir los procedimientos del estudio y se encuentra suficientemente estable para continuar en el ensayo hasta su finalización. * Si existen ambas y la diferencia es >2 semanas, conforme a la ecografía prenatal precoz. | |
E.4 | Principal exclusion criteria | 1. Infant is consuming more than 100 ml/kg/day enterally at study entry 2. Infant is not dependent on any parenteral amino acids/lipids as nutrition 3. Major congenital malformation (e.g., Infants with genetic, metabolic, and/or endocrine disorder diagnosed before enrolment). 4. Intra-uterine growth restriction (IUGR) defined as weight for gestational age less than the third percentile according to Fenton preterm growth chart (see Appendix D). 5. Confirmed necrotizing enterocolitis (NEC).1 6. Maternal diabetes (Type I/II or gestational) requiring insulin during pregnancy or in mothers past medical history. 7. suspected or confirmed Hyperinsulinemia requiring glucose administration of more than 12 mg/kg/min at randomization. 8. Any systemic insulin administration at randomization. 9. Never anything per os (NPO) until 120 hrs post-birth for any reason. 10. Heart and chest compression or any resuscitation drugs given to the infant during delivery. 11. Subjects at risk for significant GI complications such as twin-to-twin transfusion syndrome (TTTS) or monochorionic monoamniotic twins. 12. Participation in another interventional clinical study that may interfere with the primary and secondary outcomes of this trial. | 1.El lactante consume más de 100 ml/kg/día por vía enteral al incorporarse al estudio. 2.El lactante no depende de aminoácidos/lípidos parenterales como nutrición. 3.Malformación congénita importante (p. ej., lactantes con trastorno genético, metabólico o endocrino diagnosticado antes de la inclusión). 4.Restricción del crecimiento intrauterino (RCIU) definida como un peso para una edad gestacional inferior al tercer percentil según la gráfica de crecimiento prematuro de Fenton (véase el apéndice D). 5.Enterocolitis necrosante (ECN) confirmada. 6.Diabetes materna (de tipo 1/2 o gravídica) con necesidad de insulina durante el embarazo o en madres con antecedentes médicos. 7.Sospecha de hiperinsulinemia o hiperinsulinemia confirmada con necesidad de administración de más de 12 mg/kg/min de glucosa en el momento de la aleatorización. 8.Administración de cualquier insulina sistémica en la aleatorización. 9.Nunca nada por vía oral hasta 120 horas después del parto por cualquier motivo. 10.Se han administrado compresión coronaria o torácica o fármacos de reanimación al recién nacido durante el parto. 11.Sujetos con riesgo de complicaciones GI importantes, como síndrome de transfusión fetofetal (STFF) o gemelos monoamnióticos monocoriónicos. 12.Participación en otro estudio clínico intervencionista que pueda interferir en los criterios de valoración principal y secundarios de este ensayo. | |
E.5 End points |
E.5.1 | Primary end point(s) | Numbers of days to achieve full enteral feeding, defined as the first day of ability of the preterm infant to achieve enteral feeding of at least 150 ml/kg/day for three consecutive days. | Número de días hasta alcanzar la nutrición enteral completa, definido como el primer día de capacidad del lactante prematuro para alcanzar una alimentación enteral mínima de 150 ml/kg al día durante tres días consecutivos. | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | During the study (first day of ability of the preterm infant to achieve enteral feeding of at least 150 ml/kg/day for three consecutive days) | Durante el estudio (primer día de la capacidad del bebé prematuro para lograr una alimentación enteral de al menos 150 ml/kg/día durante tres días consecutivos). | |
E.5.2 | Secondary end point(s) | 1. Number of days until wean off PN (total cessation) 2. Number of days from randomization to discharge home 3. Incidence and severity of Necrotizing Enterocolitis (NEC) o Incidence of modified Bell’s stage grade >=2 of Necrotizing Enterocolitis (NEC) in infants born at 26-28 weeks GA. o Distribution of severity of Necrotizing Enterocolitis (NEC) according to modified Bell’s staging in infants born at 26-28 weeks GA who experienced NEC. o Incidence of modified Bell’s stage grade >=2 of Necrotizing Enterocolitis (NEC) in the entire study population. o Distribution of severity of Necrotizing Enterocolitis (NEC) according to modified Bell’s staging in infants who experienced NEC in the entire study population. 4. Percentage of infants reaching full enteral feeding within 6, 8, and 10 days from initiation of treatment. 5. Number of days to 120 ml/kg/day for three consecutive days 6. Number of days until PN wean off (time to amino acids and lipids withdrawal) 7. Percentage of infants weaned off PN within 4, 6, and 8 days from initiation of treatment 8. Percent enteral/ parenteral feedings from total nutrition over time 9. Number of days to discharge from primary hospital. 10. Anthropometrics 11. Number of events of culture proven nosocomial Sepsis 12. Percentage of subjects experiencing one of the adverse events of relevance (NEC, Infections, Death) 13. Retinopathy of prematurity (ROP) activity score (Appendix ) at 30-36 weeks PMA | 1.Número de días hasta la suspensión de la NP (interrupción total). 2.Número de días desde la aleatorización hasta el alta. 3.Incidencia y gravedad de la enterocolitis necrosante (ECN). oIncidencia de enterocolitis necrosante (ECN) en estadio de Bell modificado ≥2 en lactantes nacidos con una EG de 26-28 semanas. oDistribución de la gravedad de la enterocolitis necrosante (ECN) según la estadificación de Bell modificada en lactantes nacidos con EG de 26-28 semanas que presentaron ECN. oIncidencia de enterocolitis necrosante (ECN) en estadio de Bell modificado ≥2 en toda la población del estudio. oDistribución de la gravedad de la enterocolitis necrosante (ECN) según la estadificación de Bell modificada en los lactantes que presentaron ECN en toda la población del estudio. 4.Número y porcentaje de lactantes que alcanzaran la nutrición enteral completa en los 6, 8 y 10 días siguientes al inicio del tratamiento. 5.Número de días hasta 120 ml/kg/día durante tres días consecutivos. 6.Número de días hasta el abandono de la NP (tiempo hasta la retirada de aminoácidos y lípidos). 7.Porcentaje de lactantes que dejaron de recibir NP en los 4, 6 y 8 días siguientes al inicio del tratamiento. 8.Porcentaje de tomas enterales/parenterales respecto a la nutrición total a lo largo del tiempo. 9.Número de días hasta el alta del hospital principal. 10.Antropometría. 11.Número de episodios de sepsis nosocomial confirmada por cultivo. 12.Porcentaje de sujetos que sufrieron uno de los acontecimientos adversos de interés (ECN, infecciones, muerte). 13.Puntuación de actividad de la retinopatía del prematuro (RP) (apéndice ) a las 30-36 semanas de EPM. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | During the study. | Durante el estudio. | |
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 | No |
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 | 6 |
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 | Israel | United States | France | Sweden | Netherlands | Spain | Italy | |
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 | LVLS | Última visita del último paciente. | |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |