Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to assess the efficacy of aflibercept compared to laser in patients diagnosed with retinopathy of prematurity (ROP). The secondary objectives of the study are to assess the need for a second treatment modality, to assess the recurrence of ROP in the study and to assess the safety and tolerability of aflibercept.

Official Title
-----------------
Randomized, Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity

Conditions
-----------------
Retinopathy of Prematurity

Intervention / Treatment
-----------------
* Drug: aflibercept
* Procedure: laser photocoagulation


Participation Criteria
=================
Eligibility 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) 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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aflibercept Group<br>Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline. | Drug: aflibercept<br>* Administered IVT<br>* Other names: BAY86-5321;|
| Experimental: Laser Group<br>Patients will undergo laser treatment in each eligible eye at baseline. | Procedure: laser photocoagulation<br>* Transpupillary conventional laser will be administered according to standard local procedures.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Absence of Active Retinopathy of Prematurity (ROP) and Unfavorable Structural Outcomes From Baseline to Week 52 of Chronological Age | Active ROP was ROP requiring treatment and unfavorable structural outcome was defined as retinal detachment, macular dragging, macular fold, or retrolental opacity. For participants with both eyes enrolled in the study, both eyes must have met the endpoint. Participants with only one study eye enrolled were responders if the respective eye responded. | Baseline to week 52 of chronological age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Requiring Intervention With a Second Treatment Modality From Baseline to Week 52 of Chronological Age | Second treatment modality includes any treatment in addition to that assigned to the participant at baseline. This includes per-protocol rescue treatment (laser for aflibercept group, aflibercept for laser group), anti-VEGF agents not part of study protocol (e.g., bevacizumab, ranibizumab, commercially-available aflibercept not provided as study medication), or any ocular surgery for the management of any retinal pathology secondary to ROP (e.g., victrectomy, scleral buckle for retinal detachments). | Baseline to to week 52 of chronological age | 
| Percentage of Participants With Recurrence of ROP Through Week 52 of Chronological Age | Recurrence of disease is defined as the reappearance of the disease requiring further treatment (including retreatment or rescue), where both presence of ROP and presence of active ROP requiring treatment are marked as Yes, after initial regression. Here, the initial regression is defined as, at a particular visit, absence of ROP or ROP treatment not required for active ROP, i.e., presence of ROP is marked as No or the presence of active ROP requiring treatment is marked as No. | Baseline to week 52 of chronological age | 
| Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |  | Baseline to Week 52 of chronological age | 
| Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs |  | Baseline to Week 52 of chronological age |