E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Retinopathy of prematurity (ROP) |
|
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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038933 |
E.1.2 | Term | Retinopathy of prematurity |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
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 aflibercept compared to laser in patients diagnosed with retinopathy of prematurity (ROP) |
|
E.2.2 | Secondary objectives of the trial |
-To assess the need for a second treatment modality
-To assess the recurrence of ROP in the study
-To assess the safety and tolerability of aflibercept |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria:
•Gestational age at birth ≤32 weeks or birth weight ≤1500 g
•Patients with treatment-naïve retinopathy of prematurity (ROP) classified according to the International Classification for ROP in at least one eye as:
◦Zone I Stage 1 plus, or 2 plus, or 3 non-plus or 3 plus, or
◦Zone II Stage 2 plus or 3 plus, or
◦Aggressive posterior retinopathy of prematurity (AP-ROP) |
|
E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
•Known or suspected chromosomal abnormality, genetic disorder, or syndrome
•Previous exposure to any Intravitreal (IVT) or systemic anti-vascular endothelial growth factor (VEGF) agent, including maternal exposure during pregnancy and/or during breastfeeding
•Clinically significant neurological disease (eg, intraventricular hemorrhage grade 3 or higher, periventricular leukomalacia, congenital brain lesions significantly impairing optic nerve function, severe hydrocephalus with significantly increased intracranial pressure)
•Pediatric conditions rendering the infant ineligible for study intervention at baseline or for repeated blood draws as evaluated by a neonatal intensive care unit specialist and a study ophthalmologist
•Presence of active ocular infection within 5 days of the first treatment
•Advanced stages of ROP with partial or complete retinal detachment (ROP stage 4 and stage 5)
•ROP involving only Zone III
NOTE: Other protocol defined inclusion/exclusion criteria apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with absence of active retinopathy of prematurity (ROP) and of unfavorable structural outcomes (For patients with both eyes enrolled in the study, both eyes must meet the endpoint) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Week 52 of chronological age |
|
E.5.2 | Secondary end point(s) |
1) Proportion of patients requiring intervention with a second treatment modality
2) Proportion of patients with recurrence of ROP
3) Proportion of patients with ocular treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
4) Proportion of patients with systematic TEAEs and SAEs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1,3,4: Baseline to Week 52 of chronological age
2: Through Week 52 of chronological age |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
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 | No |
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 |
|
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Bulgaria |
Colombia |
Czech Republic |
Greece |
Hungary |
Italy |
Korea, Republic of |
Portugal |
Romania |
Russian Federation |
Slovakia |
Spain |
Taiwan |
Thailand |
Turkey |
United States |
Vietnam |
|
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
|
The end of the study as a whole is defined as the date of the last visit of the last patient in the study in all centers in all participating countries. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |