E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of growth retardation due to lack of bile salt-stimulated lipase in enteral nutrition |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
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 |
The primary objective of this study is to demonstrate that rhBSSL improves growth in preterm infants as compared with placebo when administered in infant formula or PBM. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are • To determine the effect of rhBSSL treatment in decreasing the risk of growth restriction • To determine the effect of rhBSSL treatment in shortening the time of hospital stay • To determine the effect of rhBSSL treatment in improving early development • To determine the effect of rhBSSL treatment in decreasing re-admittance to hospital • To determine the effect of rhBSSL treatment in increasing the levels of DHA and AA • To compare the safety and tolerability of rhBSSL treatment with that of placebo treatment • To determine the effect of rhBSSL treatment on neurodevelopment • To determine the long-term effect of rhBSSL treatment on anthropometrics • To determine the long-term safety of rhBSSL treatment • To assess the effect of rhBSSL treatment on health care utilization • To assess the effect of rhBSSL treatment on indirect resource use • To assess the effect of rhBSSL treatment on chronic medical conditions/disgnoses
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Preterm infant born before Week 32 of gestation. 2. Preterm infant who is <33 weeks postmenstrual age at the time of randomization. 3. Preterm infant who is AGA or SGA at birth. 4. Preterm infant who is receiving food enterally (bottle or gavage tube) at a level of at least 100 mL/kg/day at randomization. 5. Preterm infant whose enteral feeding consists of only infant formula or only PBM at the time of inclusion, and who are expected to remain on only infant formula for 4 weeks, or only PBM for at least 2 weeks following treatment initiation. 6. Preterm infant who is expected not to receive any fresh breast milk for 4 weeks following treatment initiation. 7. Informed consent is obtained from the patient’s legally acceptable representative. Every effort will be made to ensure informed consent is obtained from both parents. Where this is not possible, the local regulations will be followed in the definition of legally acceptable representative.
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E.4 | Principal exclusion criteria |
1. Expected stay at the hospital is less than 4 weeks from the first dose of study drug. 2. Currently receiving mechanical ventilation via endotracheal tube (continuous positive airway pressure [CPAP] or high-flow nasal cannula are not criteria for exclusion). 3. Require ≥30% oxygen (if on CPAP or in head box) or >0.5 L/min oxygen. 4. Evidence of severe brain disease or damage, including grade III or IV peri- or intraventricular hemorrhage, meningitis or hydrocephalus, grade III or IV intracranial hemorrhage, or periventricular leukomalacia. 5. Presence of major dysmorphology or congenital abnormalities that are likely to affect growth and/or development. 6. Current clinical evidence of hemodynamically significant persistent ductus arteriosus. 7. Clinical evidence of sepsis (including low or high white blood cell count and/or low platelet count and bacteriologically proven evidence of systemic infection). This should be based on the investigator’s opinion and available local laboratory reference ranges. Patients should not have received antibiotics in preceding 48 hours except where these are being administered for prophylaxis as per routine unit protocols (eg, antifungal prophylaxis with fluconazole). 8. Evidence of congenital infection (eg, cytomegalovirus). 9. Previous or current diagnosis of necrotizing enterocolitis (Bell’s stage 2 or greater). 10. Prior or current treatment with corticosteroids, except hydrocortisone. 11. Presence of any condition that in the opinion of the investigator makes the patient unsuitable for inclusion. 12. Enrolled in another concurrent clinical intervention study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is growth velocity in grams per kilogram per day during 4 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy measurement (growth velocity) will be made by frequent (at least 3 times per week) measurements of the infants' weight during treatment |
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E.5.2 | Secondary end point(s) |
• Change from Baseline in body weight (g) at 3 months • Body weight (g) at 12 and 24 months corrected age • Change from Baseline in total body length (mm) at 4 weeks and 3 months • Body length (mm) at 12 months corrected age • Body height (cm) at 24 months corrected age • Growth restriction, defined as growth velocity <15 g per kilogram bodyweight per day during 4 weeks of treatment • Time to readiness for discharge • Time to discharge • Change from Baseline in head circumference (mm) at 4 weeks and 3 months • Head circumference (mm) at 12 and 24 months corrected age • Time from Baseline to 150 mL/kg/day of enteral feeding • Readmission to hospital within 1 month of discharge • Levels of DHA and AA at 4 weeks • Bayley Scale of Infant and Toddler Development, third edition (Bayley-III) scores for the cognitive, language, motor, social-emotional and adaptive behavior domains at 24 months corrected age • Neurodevelopment disability composite at 24 months corrected age • Child Behavior Checklist (CBCL) scores at 24 months corrected age |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please see timepoints in above description of endpoints (section E.5.2) |
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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 | 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 | 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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
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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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The end of the study is defined as the date on which the last patient completes the last visit (includes follow up visits). |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |