Trial Outcomes & Findings for An Extension Study to Evaluate Safety and Tolerability of Ranibizumab in Macular Edema Secondary to Retinal Vein Occlusion (Cohort 2) (NCT NCT01442064)

NCT ID: NCT01442064

Last Updated: 2012-01-10

Results Overview

Number of participants with: any ocular adverse events, ocular adverse events causing treatment discontinuation, ocular serious adverse events, intraocular inflammation and cataracts that occurred in the study eye. Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded.

Recruitment status

COMPLETED

Study phase

Target enrollment

608 participants

Primary outcome timeframe

Up to 24 months

Results posted on

2012-01-10

Participant Flow

This is an open label multi-center extension study for participants who completed FVF4165g BRAVO (NCT00486018) or FVF4166g CRUISE (NCT0048583). Cohort 2 consists of enrolled participants with macular edema secondary to retinal vein occlusion (RVO).

Participant milestones

Participant milestones
Measure	Ranibizumab (Sham BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.
Overall Study STARTED	97	103	104	98	107	99
Overall Study Ranibizumab-Treated Subjects	93	103	104	96	107	99
Overall Study Received Study Drug in Extension Study	61	70	60	70	89	81
Overall Study COMPLETED	0	2	0	0	1	0
Overall Study NOT COMPLETED	97	101	104	98	106	99

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab (Sham BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.
Overall Study Adverse Event	2	2	2	1	2	0
Overall Study Death	0	1	3	3	1	3
Overall Study Lost to Follow-up	5	5	1	1	3	3
Overall Study Physician Decision	1	1	2	3	3	1
Overall Study Withdrawal by Subject	6	3	2	2	2	1
Overall Study Sponsor decision	82	88	92	88	95	87
Overall Study Subject non-compliance	0	0	0	0	0	2
Overall Study Condition mandated other intervention	1	1	2	0	0	2

Baseline Characteristics

An Extension Study to Evaluate Safety and Tolerability of Ranibizumab in Macular Edema Secondary to Retinal Vein Occlusion (Cohort 2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab (Sham BRAVO) n=97 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participant received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=98 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Total n=608 Participants Total of all reporting groups
Age, Customized <45 years	5 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	8 participants n=4 Participants	3 participants n=21 Participants	4 participants n=8 Participants	26 participants n=8 Participants
Age, Customized 45 to <65 years	43 participants n=5 Participants	39 participants n=7 Participants	38 participants n=5 Participants	37 participants n=4 Participants	26 participants n=21 Participants	32 participants n=8 Participants	215 participants n=8 Participants
Age, Customized 65 to <85 years	45 participants n=5 Participants	54 participants n=7 Participants	55 participants n=5 Participants	49 participants n=4 Participants	68 participants n=21 Participants	59 participants n=8 Participants	330 participants n=8 Participants
Age, Customized ≥85 years	4 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants	4 participants n=4 Participants	10 participants n=21 Participants	4 participants n=8 Participants	37 participants n=8 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	57 Participants n=7 Participants	46 Participants n=5 Participants	41 Participants n=4 Participants	52 Participants n=21 Participants	39 Participants n=8 Participants	278 Participants n=8 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	46 Participants n=7 Participants	58 Participants n=5 Participants	57 Participants n=4 Participants	55 Participants n=21 Participants	60 Participants n=8 Participants	330 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: Ranibizumab- Treated Participants includes all participants who received Ranibizumab in one of the initial studies or this extension study. This analysis includes only those adverse events that occurred during this extension study.

Outcome measures

Outcome measures
Measure	Ranibizumab (Sham BRAVO) n=93 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=96 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.
Number of Participants With Ocular Adverse Events in the Study Eye Any ocular adverse event (AE)	51 participants	64 participants	63 participants	60 participants	67 participants	66 participants
Number of Participants With Ocular Adverse Events in the Study Eye Ocular AE leading to treatment discontinuation	1 participants	2 participants	2 participants	0 participants	2 participants	2 participants
Number of Participants With Ocular Adverse Events in the Study Eye Ocular serious adverse event	2 participants	4 participants	6 participants	5 participants	10 participants	3 participants
Number of Participants With Ocular Adverse Events in the Study Eye Intraocular inflammation	0 participants	0 participants	0 participants	2 participants	3 participants	1 participants
Number of Participants With Ocular Adverse Events in the Study Eye Cataract	6 participants	10 participants	6 participants	3 participants	6 participants	5 participants

PRIMARY outcome

Timeframe: Up to 24 months

Number of participants with non-ocular adverse events (not occurring in the eye) in the following categories: any adverse events, serious adverse events, adverse events leading to study discontinuation and death. Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded. Additional information about adverse events can be found in the adverse events section.

Outcome measures

Outcome measures
Measure	Ranibizumab (Sham BRAVO) n=93 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=96 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.
Number of Participants With Non-ocular Adverse Events Any non-ocular adverse event	56 participants	77 participants	68 participants	58 participants	71 participants	64 participants
Number of Participants With Non-ocular Adverse Events Serious non-ocular adverse event	10 participants	15 participants	18 participants	16 participants	21 participants	20 participants
Number of Participants With Non-ocular Adverse Events Death	0 participants	1 participants	3 participants	3 participants	1 participants	3 participants
Number of Participants With Non-ocular Adverse Events Non-ocular adverse event led to discontinuation	1 participants	0 participants	1 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 0 of extension study), Months 6, 12, 18, and 24

Population: Enrolled participants for whom data was available for analyses at the given time-points. Observed data were used with no imputation. The number of participants for whom data was available for analyses is represented by "n".

Change from baseline in then BCVA was assessed by the number of letters a patient could read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart at a Starting Test Distance of 4 Meters. An increase in the number of letters read indicates improvement in visual acuity.

Outcome measures

Outcome measures
Measure	Ranibizumab (Sham BRAVO) n=97 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=98 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.
Change From Baseline in the Best Corrected Visual Acuity (BCVA) Month 12 (n=66,66,73,58,69,50)	0.9 letters Standard Deviation 6.9	-2.3 letters Standard Deviation 11.5	-0.7 letters Standard Deviation 7.3	-4.2 letters Standard Deviation 11.3	-5.2 letters Standard Deviation 13.8	-4.1 letters Standard Deviation 12.9
Change From Baseline in the Best Corrected Visual Acuity (BCVA) Month 6 (n=88,96,98,90,101,91)	-0.1 letters Standard Deviation 8.1	-2.2 letters Standard Deviation 10.5	-1.3 letters Standard Deviation 7.1	-3.2 letters Standard Deviation 10.4	-4.1 letters Standard Deviation 10.7	-3.2 letters Standard Deviation 9.7
Change From Baseline in the Best Corrected Visual Acuity (BCVA) Month 18 (n=23,26,32,31,26,22)	0.5 letters Standard Deviation 5.0	-1.7 letters Standard Deviation 6.3	-6.1 letters Standard Deviation 15.5	-5.1 letters Standard Deviation 14.6	-6.1 letters Standard Deviation 12.1	-0.8 letters Standard Deviation 10.9
Change From Baseline in the Best Corrected Visual Acuity (BCVA) Month 24 (n=0,2,0,0,1,0)	NA letters Standard Deviation NA No participants with data available for this time point.	-4.5 letters Standard Deviation 16.3	NA letters Standard Deviation NA No participants with data available for this time point.	NA letters Standard Deviation NA No participants with data available for this time point.	-1.0 letters Standard Deviation NA Only 1 participant in this group. Standard deviation not calculated.	NA letters Standard Deviation NA No participants with data available for this time point.

SECONDARY outcome

Timeframe: Baseline (Day 0 of extension study), Months 6 and 12

Population: Enrolled participants for whom data was available for analyses at the given time-point as indicated by "n" in the categories. Observed data were used with no imputation.

Change from baseline in Central foveal (retinal) thickness was assessed by Optical Coherence Tomography (OCT). OCT was conducted at the study sites by personnel who were certified by the University of Wisconsin Fundus Photograph Reading Center.

Outcome measures

Outcome measures
Measure	Ranibizumab (Sham BRAVO) n=97 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=98 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.
Change From Baseline in Central Foveal Thickness at Month 6 and Month 12 Month 6 (n=86,96,97,90,101,89)	21.5 µm Standard Deviation 131.6	36.8 µm Standard Deviation 159.8	40.2 µm Standard Deviation 117.4	87.4 µm Standard Deviation 217.1	161.4 µm Standard Deviation 289.1	94.6 µm Standard Deviation 235.9
Change From Baseline in Central Foveal Thickness at Month 6 and Month 12 Month 12 (n=62,65,72,56,69,51)	3.7 µm Standard Deviation 124.9	6.3 µm Standard Deviation 163.7	35.3 µm Standard Deviation 110.6	79.7 µm Standard Deviation 199.4	88.3 µm Standard Deviation 262.9	68.4 µm Standard Deviation 252.7

SECONDARY outcome

Timeframe: Baseline (Day 0 of extension study), Months 12 and 24

NEI VFQ-25 is a 25 item questionnaire that assesses visual function and quality of life for a total possible score of 0 to 100. A higher score represents better functioning. The change from baseline is calculated at Month 12 and Month 24. Participants are grouped according to the treatment they received in initial studies FVF4165g BRAVO (NCT00486018) and FVF4166g CRUISE (NCT00485836).

Outcome measures

Outcome measures
Measure	Ranibizumab (Sham BRAVO) n=97 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.	Ranibizumab (0.3 mg BRAVO) n=103 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (0.5 mg BRAVO) n=104 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.	Ranibizumab (Sham CRUISE) n=98 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.	Ranibizumab (0.3 mg CRUISE) n=107 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg CRUISE) n=99 Participants In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.
Change From Baseline in Visual Function Composite Score, as Measured by the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Month 24 (n=0,2,0,0,1,0)	NA Scores on a scale Standard Deviation NA No participants with data available for this time point.	6.2 Scores on a scale Standard Deviation 7.4	NA Scores on a scale Standard Deviation NA No participants with data available for this time point.	NA Scores on a scale Standard Deviation NA No participants with data available for this time point.	-13.3 Scores on a scale Standard Deviation NA Only 1 participant with data available in this group. Standard deviation not calculated.	NA Scores on a scale Standard Deviation NA No participants with data available for this time point.
Change From Baseline in Visual Function Composite Score, as Measured by the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Month 12 (n=64,65,72,58,67,50)	-0.3 Scores on a scale Standard Deviation 10.0	-0.7 Scores on a scale Standard Deviation 9.7	-0.7 Scores on a scale Standard Deviation 8.6	0.1 Scores on a scale Standard Deviation 10.5	-1.0 Scores on a scale Standard Deviation 8.0	-1.6 Scores on a scale Standard Deviation 7.7

Adverse Events

Ranibizumab (Sham)

Serious events: 32 serious events

Other events: 146 other events

Deaths: 0 deaths

Ranibizumab (0.3 mg)

Serious events: 49 serious events

Other events: 179 other events

Deaths: 0 deaths

Ranibizumab (0.5 mg)

Serious events: 46 serious events

Other events: 172 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Genentech

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ranibizumab (Sham) n=189 participants at risk In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE and received Ranibizumab during the 6 month observation period of the initial study or this extension study.	Ranibizumab (0.3 mg) n=210 participants at risk In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE.	Ranibizumab (0.5 mg) n=203 participants at risk In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE.
Eye disorders CATARACT	2.1% 4/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.2% 11/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.4% 11/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders CONJUNCTIVAL HAEMORRHAGE	15.3% 29/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	17.6% 37/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	15.3% 31/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders CYSTOID MACULAR OEDEMA	4.2% 8/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	4.8% 10/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.9% 12/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders EYE PAIN	6.3% 12/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	3.3% 7/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.9% 12/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders MACULAR OEDEMA	6.9% 13/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	11.0% 23/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	9.4% 19/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders MACULOPATHY	11.1% 21/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	9.0% 19/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	9.4% 19/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders RETINAL DEPIGMENTATION	5.8% 11/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	6.2% 13/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	2.0% 4/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders RETINAL EXUDATES	5.8% 11/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.7% 12/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	7.4% 15/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders RETINAL HAEMORRHAGE	17.5% 33/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	25.7% 54/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	25.1% 51/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders RETINAL VASCULAR DISORDER	10.1% 19/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	13.8% 29/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	10.3% 21/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders VISUAL ACUITY REDUCED	3.7% 7/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	6.7% 14/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	3.0% 6/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Eye disorders VITREOUS DETACHMENT	4.8% 9/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	4.3% 9/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	7.4% 15/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Infections and infestations BRONCHITIS	3.7% 7/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	3.8% 8/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.4% 11/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Infections and infestations NASOPHARYNGITIS	7.4% 14/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	6.2% 13/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	3.9% 8/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Infections and infestations SINUSITIS	4.2% 8/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.2% 11/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	4.4% 9/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Infections and infestations URINARY TRACT INFECTION	3.7% 7/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.7% 12/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	4.9% 10/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Investigations INTRAOCULAR PRESSURE INCREASED	4.8% 9/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	7.1% 15/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	5.9% 12/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.
Vascular disorders HYPERTENSION	7.4% 14/189 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	10.0% 21/210 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.	7.4% 15/203 • Up to 24 months Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.