E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Necrotizing Enterocolitis (NEC) |
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E.1.1.1 | Medical condition in easily understood language |
Necrotizing Enterocolitis (NEC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052818 |
E.1.2 | Term | Necrotizing enterocolitis neonatal |
E.1.2 | System Organ Class | 100000004856 |
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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 the efficacy of IBP-9414 vs. placebo on the prevention of necrotizing enterocolitis and on sustained feeding tolerance in very low birth weight premature infants as well as the safety of IBP-9414 vs. placebo. The study is powered on the necrotizing enterocolitis endpoint. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of IBP-9414 on different severities of NEC, all cause mortality, duration of hospitalization, growth and feeding tolerance in very low birth weight premature infants. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for the study, subjects must fulfill the following criteria: 1. Gestational age at birth of 23 weeks + 0 days -32 weeks + 0 days 2. Birth weight 500-1500g (First infants with birth weights 750-1000g will be included. After a DMC recommendation, infants with birth weights 500-1000g will then be included. After 1400 subjects in the study, infants with birth weights 500-1500g will then be included.) 3. ≤ 48 hours of age 4. Written informed consent from the subject´s legally authorized representative (LAR) |
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E.4 | Principal exclusion criteria |
Subjects will be excluded if one of the following criteria is fulfilled: 1. Participation in any other interventional clinical trial 2. Infants in extremis to whom no further intensive care is offered by attending neonatologist (e.g., infant being provided only hospice/comfort care) 3. Infants with, or at a high probability for, early onset sepsis (positive blood cultures or with clinical/histological chorioamnionitis (according to Higgins et al, 2016), and with the expectation of empirical antimicrobial therapy for > five days) 4. Infants with recognized chromosomal anomalies 5. Congenital or acquired gastrointestinal disease 6. Earlier or planned administration of formulas, foods or supplements that contain added live bacteria, including all infant formulas or food supplement products with added so-called "probiotic" or added live bacterial content during the study 7. Infants with known positive maternal HIV status |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint There are 2 primary endpoint: Primary Endpoint 1: Confirmed NEC Necrotizing enterocolitis (NEC) from the first dose until the infant reaches 34 weeks + 6 days post-menstrual age (PMA), where a NEC event is diagnosed by one of the following: A. At least one clinical sign of NEC as reported by the investigator AND abdominal X-ray evidence of intestinal pneumatosis and/or portal venous gas confirmed by independent adjudication. OR B. Surgery (or autopsy) with confirmation of necrotizing enterocolitis.
Primary Endpoint 2: Time to sustained feeding tolerance measured as the number of days from the first dose to the first day (Day F) when:
1) criteria A and B are fulfilled: A) enteral feeding at ≥120 ml/kg/day every day until the subject reaches 34w+6d post menstrual age or is discharged if earlier. B) no use of parenteral nutrition (defined as intravenous use of any macronutrients (amino and/or lipids)) until the subject reaches 34w+6d post menstrual age or is discharged if earlier. and 2) where there is weight gain between Day F and the day the subject reaches 34w+6d post menstrual age or is discharged if earlier. |
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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) |
At least one clinical sign of NEC as reported by the investigator AND abdominal X-ray evidence of intestinal pneumatosis and/or portal venous gas confirmed by independent adjudication.2. Surgery (or autopsy) with confirmation of necrotizing enterocolitis. 3. Death all causes 4. Number of days of hospitalization measured in the period from first dose to 34 weeks + 6 days PMA. 5. Weight gain in g/kg from during weeks 3 and 4 of age. 6. Number of subjects growing at ≥100 g/kg/week measured during weeks 3 and 4 of age. 7. Days with clinical signs of feeding intolerance as reported in case record form by investigator measured from the first dose of study product to 34 weeks + 6 days post-menstrual age. |
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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 | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
France |
Hungary |
Israel |
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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Last visit of the last patient |
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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 | 2 |
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 | 2 |