E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intestinal malabsorption in preterm infants |
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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. |
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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 | 10032405 |
E.1.2 | Term | Other preterm infants |
E.1.2 | System Organ Class | 100000004868 |
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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 | 10032414 |
E.1.2 | Term | Other preterm infants, less than 500 grams |
E.1.2 | System Organ Class | 100000004868 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 | 10076729 |
E.1.2 | Term | Very preterm infant |
E.1.2 | System Organ Class | 100000004868 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084217 |
E.1.2 | Term | Extremely preterm (less than 28 weeks) |
E.1.2 | System Organ Class | 100000004868 |
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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 compare the safety of treatment with ELGN-2112 to placebo in preterm infants born less than 26 weeks GA and IUGR infants<3rd percentile* born at 26-32 weeks GA. * According to Fenton preterm growth chart
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E.2.2 | Secondary objectives of the trial |
The efficacy of treatment with ELGN-2112 as compared to placebo on intestinal malabsorption in preterm infants as measured by the time to full enteral feeding Assess the Effect of ELGN-2112 on the following; ELGN-2112 compared to placebo on No of days until full wean off PN; Incidence and severity of NEC (Incidence of modified Bell’s stage grade ≥2a of NEC in the entire study population. Distribution of severity of NEC according to modified Bell’s staging in infants who experienced NEC in the entire study population); On % of infants with culture proven nosocomial sepsis; On % of infants experiencing 1 of the AE of relevance(NEC,Infection,Death); On No of days to 120 ml/kg/day for 3 consecutive days; On No of days until PN wean off; On % enteral/ parenteral feedings from total nutrition over time; On No of days to discharge from primary hospital; ELGN-2112 compared to placebo on No of days to discharge home; Anthropometrics ; ROP at 30-36 wks PMA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female preterm infant born less than 26 weeks GA (up to 25+6) or Intra-Uterine Growth Restricted (IUGR) infants (below 3rd percentile), born between 26+0 to 31+6 GA. *Gestational age matching (±2 weeks) between maternal dates and/or early antenatal ultrasound 2. Birth weight ≥ 450g 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 feeds 8. Infant is expected to wean off parenteral nutrition (PN) at the primary hospital 9. Informed consent form signed by parents or legal guardian 10. In the Investigator’s opinion, the infant is sufficiently stable to partake in the trial to completion 11. (France only) – only participants benefiting from a health insurance plan can participate in research. * If both exist and difference > 2 weeks, based on early antenatal ultrasound
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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. For infants born under 26 weeks GA, Intra-uterine growth restriction (IUGR) defined as weight for gestational age less than the third percentile according to Fenton preterm growth chart . 5. Confirmed necrotizing enterocolitis (NEC) 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. Nothing per os (NPO) at study entry and enteral/oral supplements are not allowed 10. Subjects at risk for significant GI complications such as twin-to-twin transfusion syndrome (TTTS) or monochorionic monoamniotic twins. 11. Participation in another interventional clinical study that may interfere with the primary and secondary outcomes of this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of ELGN-2112 as compared to placebo in preterm infants born under 26 weeks GA and IUGR infants born between 26-32 weeks GA. |
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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) |
1. Number 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. 2. Number of days until wean off PN (total cessation) 3. Incidence and severity of Necrotizing Enterocolitis (NEC) a. Incidence of modified Bell’s stage grade ≥2a of NEC in the entire study population. b. Distribution of severity of NEC according to modified Bell’s staging in infants who experienced NEC in the entire study population. 4. Number of events of culture proven nosocomial Sepsis 5. Percentage of subjects experiencing one of the adverse events of relevance (NEC, Infections, Death) 6. Number of days to 120 ml/kg/day for three consecutive days 7. Number of days until PN wean off (time to amino acids and lipids withdrawal) 8. Percent enteral/ parenteral feedings from total nutrition over time 9. Number of days to discharge from primary hospital. 10. Number of days from randomization to discharge home. 11. Anthropometrics 12. Retinopathy of prematurity (ROP) activity score at 30-36 weeks PMA
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | 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 | 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 | 18 |
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 |
Austria |
France |
Germany |
Italy |
Netherlands |
Spain |
Sweden |
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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 | 4 |
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 | 4 |
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 |