Trial Outcomes & Findings for Rainbow Extension Study (NCT NCT02640664)

Last Updated: 2023-02-13

Results Overview

The VA assessment at the child's 5th birthday visit was performed using Early Treatment Diabetic Retinopathy Study (ETDRS) methodology. VA measurements were taken in a sitting position at an initial test distance of 3 meters using Lea Symbols charts. Scores represented the number of optotypes (Lea symbols) the participant identified and ranged from 0 to 100, with higher scores indicating better visual acuity. VA was tested in each eye, using the child's current refractive index. The better-seeing eye was defined as the eye with the higher ETDRS score at the 5th birthday visit. If both eyes had the same ETDRS score, then the right eye was assigned as the better-seeing eye.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

180 participants

Primary outcome timeframe

at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

Results posted on

2023-02-13

Participant Flow

Study was carried out in Austria (2), Belgium (2), Croatia (1), Czech Republic (3), Denmark (1), Egypt (1), Estonia (1), France (2), Germany (1), Greece (3), Hungary (2), India (6), Italy (4), Japan (16), Lithuania (1), Malaysia (2), Romania (3), Russian Federation (5), Saudi Arabia (1), Slovakia (1), Taiwan (2), Turkey (3), United Kingdom (2), United States of America (9)

This study was not randomized. During Epoch 1 (starting at the baseline visit for the extension study up to 40 weeks from the baseline visit in the core study) participants continued to receive treatment as in the core study (NCT02375971). During Epoch 2 (starting at the end of Epoch 1 up to participant's 5th birthday) participants no longer received treatment (the study was observational)

Participant milestones

Participant milestones
Measure	Ranibizumab 0.2 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Epoch 1 STARTED	61	65	54
Epoch 1 COMPLETED	60	65	53
Epoch 1 NOT COMPLETED	1	0	1
Epoch 2 STARTED	60	65	53
Epoch 2 COMPLETED	54	55	47
Epoch 2 NOT COMPLETED	6	10	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab 0.2 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Epoch 1 Withdrawal of informed consent	1	0	0
Epoch 1 Death	0	0	1
Epoch 2 Withdrawal of informed consent	3	4	2
Epoch 2 Subject/guardian decision	0	2	2
Epoch 2 Lost to Follow-up	3	4	1
Epoch 2 Death	0	0	1

Baseline Characteristics

Rainbow Extension Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed	Total n=180 Participants Total of all reporting groups
Age, Continuous	38.88 Weeks STANDARD_DEVIATION 7.316 • n=5 Participants	40.16 Weeks STANDARD_DEVIATION 9.836 • n=7 Participants	37.48 Weeks STANDARD_DEVIATION 8.745 • n=5 Participants	38.92 Weeks STANDARD_DEVIATION 8.739 • n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	35 Participants n=7 Participants	27 Participants n=5 Participants	94 Participants n=4 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	30 Participants n=7 Participants	27 Participants n=5 Participants	86 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	38 Participants n=5 Participants	40 Participants n=7 Participants	32 Participants n=5 Participants	110 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Asian	22 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	58 Participants n=4 Participants
Race/Ethnicity, Customized Native American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

Population: Extension Safety Set: defined as the subset of the participants from the Safety Set of the core study who entered the extension study and comprised data from both core and extension studies. The outcome measure included number of participants contributing to analysis.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=45 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=43 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=36 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Visual Acuity (VA) of the Better-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms	66.8 Score on a scale Standard Error 1.95	64.6 Score on a scale Standard Error 2.00	62.1 Score on a scale Standard Error 2.18

SECONDARY outcome

Timeframe: throughout the study, approximately 5 years

Population: Extension Safety Set: defined as the subset of the patients from the Safety Set of the core study who entered the extension study and comprised data from both core and extension studies. The outcome measure included number of participants contributing to analysis.

Number of participants with ocular AEs starting during the core study and ongoing at extension baseline, or starting on/after extension baseline were reported.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship by Preferred Term	19 Participants	26 Participants	22 Participants

SECONDARY outcome

Timeframe: throughout the study, approximately 5 years

Number of participants with non-ocular adverse events regardless of study treatment or procedure relationship (greater than or equal to 3% in any arm) by preferred term were reported.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Non-ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship (Greater Than or Equal to 3% in Any Arm) by Preferred Term	46 Participants	53 Participants	46 Participants

SECONDARY outcome

Timeframe: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

The VA assessment at the child's 5th birthday visit was performed using Early Treatment Diabetic Retinopathy Study (ETDRS) methodology. VA measurements were taken in a sitting position at an initial test distance of 3 meters using Lea Symbols charts. Scores represented the number of optotypes (Lea symbols) the participant identified and ranged from 0 to 100, with higher scores indicating better visual acuity. VA was tested in each eye, using the child's current refractive index. The worse-seeing eye was the eye with a lower ETDRS score at the 5th birthday visit. If both eyes had the same ETDRS score, then the left eye was assigned as the worse-seeing eye.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=45 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=42 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=36 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Visual Acuity (VA) of the Worse-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms	60.2 Score on a scale Standard Error 2.95	53.8 Score on a scale Standard Error 3.05	52.2 Score on a scale Standard Error 3.30

SECONDARY outcome

Timeframe: at 40 weeks post core baseline visit

Population: Extension Safety Set: defined as the subset of the patients from the Safety Set of the core study who entered the extension study and comprised data from both core and extension studies. Number analyzed represents the number of participants with at least one non-missing value for the specific category and, therefore, it's not the same as the total number of participants analyzed.

The absence of active ROP in both eyes is defined by the absence of all of the following features: (1) Vessel dilatation of plus disease in at least 2 quardrants (some persisting tortuosity is allowed), (2) Extra-retina vessels extending from the retina into the vitreous and judged to be a sign of active ROP disease.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=57 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=59 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=47 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit Absence of active ROP at 40 weeks post core baseline visit	55 Participants	58 Participants	46 Participants
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit Absence of vessel dilatation	55 Participants	58 Participants	46 Participants
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit Absence of extra-retinal vessels	57 Participants	59 Participants	47 Participants

SECONDARY outcome

Timeframe: at 52 weeks post core baseline visit

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=58 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=63 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=50 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 52 Weeks Post Core Baseline Visit	58 Participants	63 Participants	49 Participants

SECONDARY outcome

Timeframe: at or before 40 weeks post baseline visit

The absence of all ocular structural abnormalities is defined by the absence of all of the following fundus features in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit	59 Participants	61 Participants	47 Participants

SECONDARY outcome

Timeframe: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit	59 Participants	61 Participants	47 Participants

SECONDARY outcome

Timeframe: at or before 40 weeks post baseline visit

Number of participants with absence of each structural abnormality in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula, (5) Retinal detachment not involving the macula, (6) Pre-retinal fibrosis

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of substantial temporal retinal vessel	59 Participants	63 Participants	49 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of Retrolental membrane obscuring the view of the posterior pole	60 Participants	65 Participants	53 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of posterior retinal fold involving the macula	59 Participants	65 Participants	51 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of retinal detachment involving the macula	60 Participants	63 Participants	51 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of retinal detachment not involving the macula	60 Participants	62 Participants	50 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit Absence of pre-retinal fibrosis	58 Participants	60 Participants	49 Participants

SECONDARY outcome

Timeframe: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of temporal retinal vessel dragging	59 Participants	63 Participants	49 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of Retrolental membrane obscuring the view of the posterior pole	60 Participants	65 Participants	52 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of posterior retinal fold involving the macula	59 Participants	65 Participants	51 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of retinal detachment involving the macula	60 Participants	63 Participants	50 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of retinal detachment not involving the macula	60 Participants	62 Participants	50 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of pre-retinal fibrosis	58 Participants	59 Participants	48 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of optic disc pallor	60 Participants	65 Participants	52 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of optic disc swelling	60 Participants	65 Participants	53 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of pigmentary disturbance in the macula	60 Participants	64 Participants	52 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit Absence of atrophic changes in macula	60 Participants	65 Participants	51 Participants

SECONDARY outcome

Timeframe: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit	59 Participants	61 Participants	47 Participants

SECONDARY outcome

Timeframe: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=60 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=53 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of substantial temporal retinal vessel dragging	59 Participants	63 Participants	49 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of Retrolental membrane obscuring the view of the posterior pole	60 Participants	65 Participants	52 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of posterior retinal fold involving the macula	59 Participants	65 Participants	51 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of retinal detachment involving the macula	60 Participants	63 Participants	50 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of retinal detachment not involving the macula	60 Participants	62 Participants	50 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of pre-retinal fibrosis	58 Participants	59 Participants	48 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of optic disc pallor	60 Participants	65 Participants	53 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of optic disc swelling	60 Participants	65 Participants	53 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of pigmentary disturbance in the macula	60 Participants	64 Participants	52 Participants
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit Absence of atrophic changes in macula	60 Participants	65 Participants	52 Participants

SECONDARY outcome

Timeframe: up to 40 weeks post baseline visit in the core study

Recurrence of ROP was defined as ROP receiving any post-baseline intervention after the 1st study treatment in the core study. In the ranibizumab arms, post-baseline interventions were ranibizumab retreatment or switch to laser. In the laser arm, post-baseline interventions were supplementary laser treatments after 11 days post-baseline, or switch to ranibizumab; supplementary laser treatment within 11 days post-baseline was not counted as recurrence.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Recurrence of ROP up to 40 Weeks Post Baseline Visit in the Core Study	19 Participants	22 Participants	11 Participants

SECONDARY outcome

Timeframe: up to 52 weeks post baseline visit in the core study

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Recurrence of ROP up to 52 Weeks Post Baseline Visit in the Core Study	19 Participants	22 Participants	11 Participants

SECONDARY outcome

Timeframe: up to and including 40 weeks post baseline visit in the core study

Number of ranibizumab injections received in the treatment of participants with ROP up to and including 40 weeks post baseline visit in the core study were reported.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=11 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Ranibizumab Injections Received Per Participant Over the Whole Safety Observation Period	2.5 Number of injections Standard Deviation 0.96	2.5 Number of injections Standard Deviation 1.06	2.4 Number of injections Standard Deviation 0.92

SECONDARY outcome

Timeframe: at participant's 2 years corrected age (maximum 2 years and 4 months post core baseline visit)

Summary of participants was reported to evaluate the refraction in each eye at the participant's 2 years corrected age

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=57 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=54 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=47 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Refraction Status: Summary of Participants at Participant's 2 Years Corrected Age Best eye	-0.697 diopters Standard Deviation 2.7032	-0.713 diopters Standard Deviation 2.6100	-1.793 diopters Standard Deviation 4.1570
Refraction Status: Summary of Participants at Participant's 2 Years Corrected Age Worst eye	-0.825 diopters Standard Deviation 2.6575	-0.829 diopters Standard Deviation 2.8346	-1.516 diopters Standard Deviation 3.5652

SECONDARY outcome

Timeframe: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

Summary of participants was reported to evaluate the refraction in each eye at the participant's 2 years' corrected age

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=52 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=55 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=45 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Refraction Status: Summary of Participants at the Participant's Fifth Birthday Visit Best eye	-0.601 diopters Standard Deviation 2.8107	-0.859 diopters Standard Deviation 2.7406	-1.883 diopters Standard Deviation 4.4970
Refraction Status: Summary of Participants at the Participant's Fifth Birthday Visit Worst eye	-0.904 diopters Standard Deviation 2.8501	-1.074 diopters Standard Deviation 3.0405	-1.706 diopters Standard Deviation 3.5740

SECONDARY outcome

Timeframe: Baseline of the core study, at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit) and at the subjects' fifth birthday (maximum 5 years and 4 months post core baseline visit)

Population: Extension Safety Set: defined as the subset of the patients from the Safety Set of the core study who entered the extension study and comprised data from both core and extension studies. Number analyzed represents the number of participants with at least one non-missing value for the specific category and, therefore, it's not the same as the total number of participants analyzed.

Subject´s weight was reported to evaluate the physical development.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Change From Baseline in Weight Year 2	8695.9 grams Standard Deviation 1406.58	8461.7 grams Standard Deviation 1375.95	8840.6 grams Standard Deviation 1643.80
Change From Baseline in Weight 5th Birthday	14611.9 grams Standard Deviation 3018.65	14324.7 grams Standard Deviation 2616.96	14689.4 grams Standard Deviation 3300.05

SECONDARY outcome

Timeframe: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)

Subject´s head circumference was reported to evaluate the physical development.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=55 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=56 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=44 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Change From Baseline in Head Circumference	16.5 cm Standard Deviation 2.60	16.2 cm Standard Deviation 2.78	17.2 cm Standard Deviation 2.81

SECONDARY outcome

Timeframe: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)

Subject´s Sitting Diastolic Blood Pressure was reported to evaluate the physical development.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=38 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=33 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=31 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Change From Baseline in Sitting Diastolic Blood Pressure	16.7 mmHg Standard Deviation 14.92	13.6 mmHg Standard Deviation 14.10	16.5 mmHg Standard Deviation 12.14

SECONDARY outcome

Timeframe: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)

Subject´s Sitting Systolic Blood Pressure was reported to evaluate the physical development.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=38 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=32 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=31 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Change From Baseline in Sitting Systolic Blood Pressure	20.6 mmHg Standard Deviation 16.13	16.2 mmHg Standard Deviation 15.95	17.6 mmHg Standard Deviation 12.75

SECONDARY outcome

Timeframe: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

Population: Extension Safety Set: defined as the subset of the patients from the Safety Set of the core study who entered the extension study and comprised data from both core and extension studies. Number analyzed represents the number of participants with at least one non-missing value for the specific category and, therefore, it's not the same as the total number of participants analyzed.

Number of participants with respiratory function status was reported

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With the Summary of Respiratory Function Status Number of participants with presence of wheezing limiting child's speech ability	1 Participants	0 Participants	0 Participants
Number of Participants With the Summary of Respiratory Function Status Number of participants with Wheezing/whistling status	6 Participants	4 Participants	2 Participants
Number of Participants With the Summary of Respiratory Function Status Number of participants with attacks of wheezing	47 Participants	50 Participants	45 Participants
Number of Participants With the Summary of Respiratory Function Status Number of participants with frequency of sleep disturbance due to wheezing	47 Participants	52 Participants	47 Participants
Number of Participants With the Summary of Respiratory Function Status Number of participants with dry cough status at night	5 Participants	2 Participants	1 Participants
Number of Participants With the Summary of Respiratory Function Status Number of participants with presence of smoker at home	15 Participants	8 Participants	4 Participants

SECONDARY outcome

Timeframe: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)

Number of participants with hearing function status was reported

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Number of Participants With Hearing Impairment of Any Type	2 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: From baseline of the core study up to 5 years and 4 months post core baseline visit

Duration of hospitalization (from birth to first hospital discharge home) was reported to evaluate the health status of the subject

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=61 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=65 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=54 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Duration of Hospitalization	111.1 days Standard Deviation 62.27	116.2 days Standard Deviation 78.10	95.7 days Standard Deviation 57.07

SECONDARY outcome

Timeframe: From baseline of the core study up to 5 years and 4 months post core baseline visit

Weight (gram) at the time of first hospital discharge was reported to evaluate the health status of the subject

Outcome measures

Outcome measures
Measure	Ranibizumab 0.2 mg n=56 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Ranibizumab 0.1 mg n=62 Participants 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required	Laser Therapy n=51 Participants Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Weight at the Time of First Hospital Discharge	2910.9 gram Standard Deviation 1359.34	2966.5 gram Standard Deviation 1198.60	2658.7 gram Standard Deviation 926.92

Adverse Events

Ranibizumab 0.2 mg

Serious events: 21 serious events

Other events: 41 other events

Deaths: 0 deaths

Ranibizumab 0.1 mg

Serious events: 27 serious events

Other events: 46 other events

Deaths: 0 deaths

Laser Therapy

Serious events: 26 serious events

Other events: 40 other events

Deaths: 2 deaths

Total

Serious events: 74 serious events

Other events: 127 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER