E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Retinopathy of Prematurity (ROP) |
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E.1.1.1 | Medical condition in easily understood language |
Damage to the retina of the eye in preterm infants |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10015919 |
E.1.2 | Term | Eye disorders |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 |
Section A:
To establish the dose and sampling schedule to be used in Study Sections B and C
Sections B and C:
To determine the dose of IMP, administered by continuous IV infusion, required to reach and maintain a physiological range of serum IGF-1 of 20-60 µg/L, defined as the in utero levels of IGF-1 for corresponding GA in a normal population
To determine serum concentrations of IGF-1 and associated pharmacokinetic parameters after continuous IV infusion of IMP
Section D:
To determine the effect of IMP on the severity of ROP as compared to the severity of ROP in an untreated control population
To evaluate the dose of IMP administered by continuous IV infusion, required to reach and maintain a physiological range of serum IGF-1 of 28-109 µg/L To determine serum concentrations of IGF-1 and associated pharmacokinetic parameters after continuous IV infusion of IMP
To determine serum concentration of IGFBP-3 and acid labile subunit (ALS) after continuous IV infusion of IMP |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of rhIGF-1/rhIGFBP-3 on other efficacy parameters and determine the safety profile of rhIGF-1/rhIGFBP-3 when compared with standard neonatal care in preterm infants |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each subject must meet the following criteria to be enrolled in this study:
1- A signed written informed consent from the subject's parents/guardians prior to any study-related procedures that has been approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
2- Subject must be between GA of 26 weeks + 0 days and 27 weeks +6 days (Study Section A) or between GA of 23 weeks + 0 days and 27 weeks + 6 days (Study Sections B, C, and D), inclusive
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be excluded from the study:
1- Subjects born small for gestational age (SGA), ie, weight at birth <-2 SDS (Study Section A only)
2- Detectable gross malformation
3- Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the investigator’s opinion
4- Persistent plasma glucose level <2.5 mmol/L or >10 mmol/L at Study Day 0 (day of birth) to exclude severe congenital abnormalities of glucose metabolism
5- Anticipated need of administration of erythropoietin (rhEPO) during treatment with study drug
6- Maternal history of gestational diabetes or any diabetes requiring insulin while pregnant
7- Clinically significant neurological disease according to the investigator’s opinion (Stage 1 IVH allowed)
8- Any other condition or therapy that, in the investigator’s opinion, may pose a risk to the subject or interfere with the subject’s ability to be compliant with this protocol or interfere with interpretation of results
9- Monozygotic twins
10- Subject participating or plans to participate in a clinical study of another investigational study drug
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E.5 End points |
E.5.1 | Primary end point(s) |
Sections A, B, C: Primary endpoint: Severity of ROP
Sections D: Primary endpoint: Maximum severity of ROP stage across all retinal examinations |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
First ROP examination shall occur at 5 to 6 weeks or PMA 31 weeks.
Follow-up examination should occur at least 1 to 2 weeks depending upon the clinical evaluation of the paediatric ophtalmologist.
Final ROP assessment will occur at 40 weeks +/- 4 days. |
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E.5.2 | Secondary end point(s) |
The key secondary endpoint of this study is in Section D: time to discharge from the neonatal intensive care (TDNIC). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
TDNIC will be calculated from the day of birth to the day of the discharge |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Assessor-blind and comparison with untreated control group |
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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 | Yes |
E.8.2.3.1 | Comparator description |
serum concentration of IGF-1 in untreated controls |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |