Trial Outcomes & Findings for Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity (NCT NCT04101721)

Last Updated: 2023-07-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

127 participants

Primary outcome timeframe

Baseline to week 52 of chronological age

Results posted on

2023-07-20

Participant Flow

137 participants were screened, 127 were randomized.

Of the 127 participants randomized, 33 were randomized to laser and 94 were randomized to aflibercept. Six of the 33 participants randomized to laser were withdrawn before receiving any study intervention (5 due to Parent/Guardian and 1 due to Physician decision); One of the 94 participants randomized to aflibercept was withdrawn before receiving any study intervention due to Parent/Guardian. In total, 120 participants (27, laser group; 93, aflibercept group) received at least 1 study treatment.

Unit of analysis: Eyes

Participant milestones

Participant milestones
Measure	Laser Photocoagulation Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Overall Study STARTED	27 50	93 179
Overall Study COMPLETED	26 48	87 168
Overall Study NOT COMPLETED	1 2	6 11

Reasons for withdrawal

Reasons for withdrawal
Measure	Laser Photocoagulation Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Overall Study Withdrawal By Parent/Guardian	1	2
Overall Study Death	0	1
Overall Study Lost to Follow-up	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Laser Photocoagulation n=50 Eyes Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=179 Eyes Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.	Total n=229 Eyes Total of all reporting groups
Age, Continuous	11.09 Weeks STANDARD_DEVIATION 4.338 • n=5 Participants	9.76 Weeks STANDARD_DEVIATION 3.149 • n=7 Participants	10.06 Weeks STANDARD_DEVIATION 3.476 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	52 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	41 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants	72 Participants n=7 Participants	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	26 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants	44 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Retinopathy of prematurity (ROP) Zone, by eye Zone I	13 Eyes n=14 Eyes	47 Eyes n=23 Eyes	60 Eyes n=50 Eyes
Retinopathy of prematurity (ROP) Zone, by eye Zone II	37 Eyes n=14 Eyes	132 Eyes n=23 Eyes	169 Eyes n=50 Eyes

PRIMARY outcome

Timeframe: Baseline to week 52 of chronological age

Population: Full analysis set (FAS): All randomized participants who received any study treatment. Analysis on the FAS was performed according to the treatment assigned at baseline (as randomized).

Outcome measures

Outcome measures
Measure	Laser Photocoagulation n=27 Participants Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 Participants Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Percentage of Participants With Absence of Active Retinopathy of Prematurity (ROP) and Unfavorable Structural Outcomes From Baseline to Week 52 of Chronological Age	77.8 Percentage of participants	79.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to to week 52 of chronological age

Population: Full analysis set (FAS): All randomized participants who received any study treatment.

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).

Outcome measures

Outcome measures
Measure	Laser Photocoagulation n=27 Participants Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 Participants Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Percentage of Participants Requiring Intervention With a Second Treatment Modality From Baseline to Week 52 of Chronological Age	18.5 Percentage of participants	15.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to week 52 of chronological age

Population: Full analysis set (FAS): All randomized participants who received any study treatment.

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."

Outcome measures

Outcome measures
Measure	Laser Photocoagulation n=27 Participants Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 Participants Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Percentage of Participants With Recurrence of ROP Through Week 52 of Chronological Age	29.6 Percentage of participants	39.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52 of chronological age

Population: Safety analysis set (SAF): All randomized participants who received any study treatment (active or laser); it is based on the treatment actually received (as treated).

Outcome measures

Outcome measures
Measure	Laser Photocoagulation n=27 Participants Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 Participants Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) % Ocular TEAEs	25.9 Percentage of participants	18.3 Percentage of participants
Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) % Ocular TESAEs	11.1 Percentage of participants	6.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52 of chronological age

Population: Safety analysis set (SAF): All randomized participants who received any study treatment (active or laser); it is based on the treatment actually received (as treated).

Outcome measures

Outcome measures
Measure	Laser Photocoagulation n=27 Participants Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 Participants Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs % Systematic TEAEs	51.9 Percentage of participants	47.3 Percentage of participants
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs % Systematic TESAEs	7.4 Percentage of participants	12.9 Percentage of participants

Adverse Events

Laser Photocoagulation

Serious events: 12 serious events

Other events: 12 other events

Deaths: 0 deaths

Aflibercept 0.4 mg

Serious events: 32 serious events

Other events: 40 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Laser Photocoagulation n=27 participants at risk Participants received laser treatment to each eligible eye at baseline (Day 1), with supplementary laser treatments allowed. Multiple sessions within one week from baseline were counted as a single treatment. If both eyes were eligible, they were assigned to the same treatment group.	Aflibercept 0.4 mg n=93 participants at risk Participants received one intravitreal injection of aflibercept 0.4 mg (0.01 mL) per eligible eye at baseline (Day 1), with up to 2 re-injections at the same single dose allowed for each eligible eye if required and interval since last aflibercept injection was 28 or more days. If both eyes were eligible, they were assigned to the same treatment group.
Respiratory, thoracic and mediastinal disorders Wheezing	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	1.1% 1/93 • Number of events 1 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Gastrointestinal disorders Constipation	14.8% 4/27 • Number of events 5 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	4.3% 4/93 • Number of events 4 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	5.4% 5/93 • Number of events 5 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Gastrointestinal disorders Inguinal hernia	11.1% 3/27 • Number of events 3 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	4.3% 4/93 • Number of events 4 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Gastrointestinal disorders Umbilical hernia	0.00% 0/27 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	5.4% 5/93 • Number of events 5 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
General disorders Pyrexia	14.8% 4/27 • Number of events 4 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	4.3% 4/93 • Number of events 6 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Infections and infestations Bacterial disease carrier	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	1.1% 1/93 • Number of events 1 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Infections and infestations Nasopharyngitis	0.00% 0/27 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	6.5% 6/93 • Number of events 7 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Musculoskeletal and connective tissue disorders Osteopenia	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	2.2% 2/93 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Respiratory, thoracic and mediastinal disorders Apnoea	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	1.1% 1/93 • Number of events 1 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Skin and subcutaneous tissue disorders Rash	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	5.4% 5/93 • Number of events 8 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary dysplasia	0.00% 0/27 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	7.5% 7/93 • Number of events 7 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	3.2% 3/93 • Number of events 3 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Eye disorders Conjunctival haemorrhage Study Eye	0.00% 0/27 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	5.4% 5/93 • Number of events 7 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Eye disorders Strabismus Study Eye	0.00% 0/27 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	6.5% 6/93 • Number of events 9 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.
Vascular disorders Hypotension	7.4% 2/27 • Number of events 2 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.	1.1% 1/93 • Number of events 1 • From signing of informed consent form (ICF) to end of study (week 52 of chronological age visit), an average of 42 weeks Thirty-three (33) participants were randomized to laser and 94 participants randomized to aflibercept; however, 6 laser participants and 1 aflibercept participant were not treated and therefore, excluded from the safety analysis set (SAF) and FAS. SAF and FAS populations are identical: 27 laser group; 93 aflibercept group.