Trial Outcomes & Findings for To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema (NCT NCT01846299)

Last Updated: 2016-05-23

Results Overview

BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

181 participants

Primary outcome timeframe

Baseline, Month 2

Results posted on

2016-05-23

Participant Flow

A total of 181 participants were enrolled. Of these, 178 adults were randomized in a 2:1 ratio and considered for analysis. The 3 adolescent participants, non-randomized, received open-label treatment and were not included in the analyses. Therefore, the number enrolled = 181 differs from the number randomized = 178 in the participant flow.

Participant milestones

Participant milestones
Measure	Ranibizumab A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.
Overall Study STARTED	118	60
Overall Study Full Analysis Set	117	60
Overall Study Safety Set	119	58
Overall Study COMPLETED	106	50
Overall Study NOT COMPLETED	12	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.
Overall Study Physician Decision	4	2
Overall Study Protocol deviation	1	0
Overall Study Death	1	2
Overall Study Lost to Follow-up	3	0
Overall Study Withdrawal by Subject	1	6
Overall Study Adverse Event	2	0

Baseline Characteristics

To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab n=118 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Total n=178 Participants Total of all reporting groups
Age, Continuous	63.5 Years STANDARD_DEVIATION 13.97 • n=5 Participants	61.8 Years STANDARD_DEVIATION 15.55 • n=7 Participants	62.9 Years STANDARD_DEVIATION 14.50 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	23 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	37 Participants n=7 Participants	110 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 2

Population: Full analysis set: The full analysis set included all randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye	5.7 letters Standard Error 0.81	2.9 letters Standard Error 0.89	—

SECONDARY outcome

Timeframe: Baseline, Month 1, Month 2

Population: The full analysis set (FAS) was considered for the analysis. The FAS. The FAS included all randomized participants who received at least one dose of study treatment. Only participants of the FAS, who had data at baseline and the specific post-baseline time point, were included in the analysis for that time point.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Change From Baseline in BCVA in Study Eye up to Month 2 Month 1 (n=116,59)	4.7 letters Standard Error 0.70	1.4 letters Standard Error 0.98	—
Change From Baseline in BCVA in Study Eye up to Month 2 Month 2 (n=114,59)	5.8 letters Standard Error 0.76	2.8 letters Standard Error 1.05	—

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all randomized participants who received at least one dose of study treatment. Only participants of the FAS, who had data at baseline and the specific post-baseline time point, were included in the analysis for that time point.

CSFT wasassessed by optical coherence tomography (OCT). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 10 (n=103,50)	-114.1 micrometers (um) Standard Deviation 131.12	-116.6 micrometers (um) Standard Deviation 147.26	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 11 (n=101,49)	-112.1 micrometers (um) Standard Deviation 124.00	-123.5 micrometers (um) Standard Deviation 140.65	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 12 (n=103,50)	-121.0 micrometers (um) Standard Deviation 124.67	-116.8 micrometers (um) Standard Deviation 137.99	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 1 (n=112,59)	-83.6 micrometers (um) Standard Deviation 127.45	-14.3 micrometers (um) Standard Deviation 97.36	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 2 (n=112,59)	-82.5 micrometers (um) Standard Deviation 140.06	-30.6 micrometers (um) Standard Deviation 102.77	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 3 (n=113,59)	-86.5 micrometers (um) Standard Deviation 136.43	-92.2 micrometers (um) Standard Deviation 129.85	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 4 (n=109,57)	-94.5 micrometers (um) Standard Deviation 141.55	-95.5 micrometers (um) Standard Deviation 140.68	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 5 (n=105,57)	-98.6 micrometers (um) Standard Deviation 136.28	-107.6 micrometers (um) Standard Deviation 142.22	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 6 (n=109,54)	-110.6 micrometers (um) Standard Deviation 133.10	-84.1 micrometers (um) Standard Deviation 137.86	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 7 (n=105,52)	-113.3 micrometers (um) Standard Deviation 130.84	-112.9 micrometers (um) Standard Deviation 148.13	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 8 (n=105,51)	-113.1 micrometers (um) Standard Deviation 127.11	-107.7 micrometers (um) Standard Deviation 157.40	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 9 (n=105,52)	-111.6 micrometers (um) Standard Deviation 127.99	-116.3 micrometers (um) Standard Deviation 146.43	—

SECONDARY outcome

Timeframe: Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

CSFV was assessed OCT. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 1 (n=112,59)	-0.296 microliters (ul) Standard Deviation 0.4570	-0.032 microliters (ul) Standard Deviation 0.3969	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 2 (n=112,59)	-0.276 microliters (ul) Standard Deviation 0.5362	-0.104 microliters (ul) Standard Deviation 0.3958	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 3 (n=113,59)	-0.322 microliters (ul) Standard Deviation 0.5812	-0.348 microliters (ul) Standard Deviation 0.5075	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 4 (n=109,57)	-0.333 microliters (ul) Standard Deviation 0.5568	-0.378 microliters (ul) Standard Deviation 0.5436	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 5 (n=105,57)	-0.383 microliters (ul) Standard Deviation 0.5592	-0.401 microliters (ul) Standard Deviation 0.5893	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 6 (n=109,54)	-0.388 microliters (ul) Standard Deviation 0.5167	-0.344 microliters (ul) Standard Deviation 0.5530	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 7 (n=105,52)	-0.438 microliters (ul) Standard Deviation 0.5267	-0.438 microliters (ul) Standard Deviation 0.6098	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 8 (n=105,51)	-0.405 microliters (ul) Standard Deviation 0.5074	-0.421 microliters (ul) Standard Deviation 0.6484	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 9 (n=105,52)	-0.446 microliters (ul) Standard Deviation 0.6066	-0.444 microliters (ul) Standard Deviation 0.6210	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 10 (n=103,50)	-0.439 microliters (ul) Standard Deviation 0.6241	-0.433 microliters (ul) Standard Deviation 0.6407	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 11 (n=101,49)	-0.406 microliters (ul) Standard Deviation 0.4871	-0.459 microliters (ul) Standard Deviation 0.6157	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 12 (n=103,50)	-0.447 microliters (ul) Standard Deviation 0.4837	-0.455 microliters (ul) Standard Deviation 0.5910	—

SECONDARY outcome

Timeframe: Month 2, Month 6, Month 12

Population: The FAS was considered for the analysis. The FAS included all randomized participants who received at least one dose of study treatment. Only participants (n), with values 'Absent' or 'Definite' for both the baseline and corresponding post-baseline time point, were included in the analysis.

The presence of intra-retinal fluid was assessed by OCT.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 2, Absent (n=112,59)	98 Participants	46 Participants	—
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 2, Definite (n=112,59)	14 Participants	13 Participants	—
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 6, Absent (n=109,55)	97 Participants	43 Participants	—
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 6, Definite (n=109,55)	12 Participants	12 Participants	—
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 12, Absent (n=103,50)	78 Participants	39 Participants	—
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 12, Definite (n=103,50)	25 Participants	11 Participants	—

SECONDARY outcome

Timeframe: Month 2, Month 6, Month 12

The presence of subretinal fluid was assessed by OCT.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 2, Absent (n=113,59)	77 Participants	33 Participants	—
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 2, Definite (n=110,55)	36 Participants	26 Participants	—
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 6, Absent (n=109,55)	75 Participants	35 Participants	—
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 6, Definite (n=109,55)	35 Participants	20 Participants	—
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 12, Absent (n=104,50)	77 Participants	37 Participants	—
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline Month 12, Definite (n=103,50)	27 Participants	13 Participants	—

SECONDARY outcome

Timeframe: Month 2

Population: The FAS was used this analysis. The FAS included randomized participants who received at least one dose of study treatment.

The presence of active ME leakage was assessed by fluorescein angiography (FA).

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants With Presence of Active Macular Edema (ME) Leakage	96 Participants	53 Participants	—

SECONDARY outcome

Timeframe: Month 1

Population: The FAS was used for this analysis. The FAS included all randomized participants who received at least one dose of study treatment.

Rescue treatment with laser photocoagulation or periocular treatment could be administered at Month 1 only if the participant had a visual acuity loss of \> 5 letters due to disease activity from baseline to Month 1.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants Requiring Rescue Treatment at Month 1	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Baseline (BL), month 1 through month 6, month 1 through month 12

Population: The FAS was used for this analysis. The FAS included randomized participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Average Change From Baseline in BCVA Average change from BL, month 1 through month 6	6.39 letters Standard Deviation 8.405	4.50 letters Standard Deviation 8.095	—
Average Change From Baseline in BCVA Average change from BL, month 1 through month 12	7.40 letters Standard Deviation 9.052	5.82 letters Standard Deviation 8.927	—

SECONDARY outcome

Timeframe: Month 2, Month 6 , Month 12

VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, Gain of >= 15 letters (n=114,59)	26 Participants	7 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, Gain of >= 10 letters (n=114,59)	35 Participants	11 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, Gain of >= 5 letters (n=114,59)	55 Participants	19 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, Gain of >= 1 letter (n=114,59)	80 Participants	38 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, Gain of >= 15 letters (n=111,55)	30 Participants	15 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, Gain of >= 10 letters (n=111,55)	41 Participants	21 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, Gain of >= 5 letters (n=111,55)	67 Participants	34 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, Gain of >= 1 letters (n=111,55)	87 Participants	40 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, Gain of >= 15 letters (n=106,50)	44 Participants	22 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, Gain of >= 10 letters (n=106,50)	55 Participants	27 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, Gain of >= 5 letters (n=106,50)	72 Participants	37 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, Gain of >= 1 letters (n=106,50)	86 Participants	42 Participants	—

SECONDARY outcome

Timeframe: Month 2, Month 6, Month 12

VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters.

Outcome measures

Outcome measures
Measure	Ranibizumab n=117 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=60 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab Participants did not receive ranibizumab at any time during the study.
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, Loss of >1 letter (n=114,59)	17 Participants	9 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, Loss of >5 letters (n=114,59)	8 Participants	4 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, Loss of >10 letters (n=114,59)	2 Participants	3 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, Loss of >15 letters (n=114,59)	0 Participants	0 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, Loss of >1 letter (n=111,55)	14 Participants	12 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, Loss of >5 letters (n=111,55)	5 Participants	7 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, Loss of >10 letters (n=111,55)	3 Participants	4 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, Loss of >15 letters (n=111,55)	1 Participants	1 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, Loss of >= 1 letter (n=106,50)	10 Participants	5 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, Loss of >= 5 letters (n=106,50)	6 Participants	3 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, Loss of >= 10 letters (n=106,50)	2 Participants	3 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, Loss of >= 15 letters (n=106,50)	1 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Month 12

Population: The safety set was used for this analysis. The safety set included randomized participants who received at least one dose of study treatment. Two participants from the sham group were included in the ranibizumab group based on the actual treatment received.

The number of participants administered study treatments, according to treatment frequency, was assessed.

Outcome measures

Outcome measures
Measure	Ranibizumab n=119 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=56 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab n=2 Participants Participants did not receive ranibizumab at any time during the study.
Number of Participants With Ranibizumab Treatments Frequency of injections = 9	3 Participants	6 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 0	0 Participants	0 Participants	2 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 1	13 Participants	6 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 2	5 Participants	3 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 3	14 Participants	7 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 4	3 Participants	5 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 5	17 Participants	7 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 6	7 Participants	11 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 7	6 Participants	0 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 8	13 Participants	0 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 10	12 Participants	11 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 11	6 Participants	0 Participants	0 Participants
Number of Participants With Ranibizumab Treatments Frequency of injections = 12	20 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 6, month 12

The number of participants, administered re-treatments according to treatment frequency, was assessed. Re-treatment was defined as an administration of study medication following at least one non-missed visit where treatment was not administered in the study eye. Up to Month 12, the maximum number of retreatments was 5.

Outcome measures

Outcome measures
Measure	Ranibizumab n=119 Participants A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=56 Participants Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab n=2 Participants Participants did not receive ranibizumab at any time during the study.
Number of Participants With Re-treatments Month 6, Frequency of re-treatment = 1	34 Participants	15 Participants	0 Participants
Number of Participants With Re-treatments Month 6, Frequency of re-treatment = 2	15 Participants	3 Participants	0 Participants
Number of Participants With Re-treatments Month 12, Frequency of re-treatment = 1	21 Participants	12 Participants	0 Participants
Number of Participants With Re-treatments Month 12, Frequency of re-treatment = 2	24 Participants	7 Participants	0 Participants
Number of Participants With Re-treatments Month 12, Frequency of re-treatment = 3	13 Participants	5 Participants	0 Participants
Number of Participants With Re-treatments Month 12, Frequency of re-treatment = 4	5 Participants	5 Participants	0 Participants
Number of Participants With Re-treatments Month 12, Frequency of re-treatment = 5	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

The total number of primary reasons for decisions to treat was assessed. A single participant could have had multiple primary reasons for treatment.

Outcome measures

Outcome measures
Measure	Ranibizumab n=689 Reasons A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Sham With Ranibizumab n=372 Reasons Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At Month 1, if treatment was needed, sham was administered. At Month 2, participants could switch to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab n=1 Reasons Participants did not receive ranibizumab at any time during the study.
Number of Primary Reasons for Decision to Treat by Investigator OCT abnormality	637 Number of primary reasons	345 Number of primary reasons	1 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator Vision impairment	38 Number of primary reasons	22 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator FA abnormality	11 Number of primary reasons	5 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator Color fundus photography abnormality	0 Number of primary reasons	0 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator Clinical abnormality	3 Number of primary reasons	0 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator Without documentation (missing reason)	0 Number of primary reasons	0 Number of primary reasons	0 Number of primary reasons

Adverse Events

Ranibizumab 0.5mg

Serious events: 15 serious events

Other events: 58 other events

Deaths: 0 deaths

Sham With Ranibizumab 0.5mg

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Sham Without Ranibizumab 0.5mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ranibizumab 0.5mg n=119 participants at risk Ranibizumab 0.5mg	Sham With Ranibizumab 0.5mg n=56 participants at risk Sham with Ranibizumab 0.5mg	Sham Without Ranibizumab 0.5mg n=2 participants at risk Sham without Ranibizumab 0.5mg
Cardiac disorders Atrial fibrillation	0.84% 1/119	0.00% 0/56	0.00% 0/2
Cardiac disorders Cardio-respiratory arrest	0.00% 0/119	1.8% 1/56	0.00% 0/2
Eye disorders Conjunctivitis allergic (Fellow treated eye)	0.84% 1/119	0.00% 0/56	0.00% 0/2
Eye disorders Conjunctivitis allergic (Study eye)	0.84% 1/119	0.00% 0/56	0.00% 0/2
Eye disorders Corneal oedema (Fellow treated eye)	0.00% 0/119	1.8% 1/56	0.00% 0/2
Eye disorders Open angle glaucoma (Fellow untreated eye)	0.84% 1/119	0.00% 0/56	0.00% 0/2
Eye disorders Open angle glaucoma (Study eye)	0.84% 1/119	0.00% 0/56	0.00% 0/2
Gastrointestinal disorders Gastritis	0.00% 0/119	1.8% 1/56	0.00% 0/2
Gastrointestinal disorders Intestinal obstruction	0.84% 1/119	0.00% 0/56	0.00% 0/2
Gastrointestinal disorders Pancreatitis acute	0.00% 0/119	1.8% 1/56	0.00% 0/2
General disorders Hypothermia	0.84% 1/119	0.00% 0/56	0.00% 0/2
Hepatobiliary disorders Biliary colic	0.84% 1/119	0.00% 0/56	0.00% 0/2
Immune system disorders Anaphylactic reaction	0.84% 1/119	0.00% 0/56	0.00% 0/2
Infections and infestations Endophthalmitis (Study eye)	0.84% 1/119	0.00% 0/56	0.00% 0/2
Infections and infestations Herpes zoster cutaneous disseminated	0.84% 1/119	0.00% 0/56	0.00% 0/2
Infections and infestations Pneumonia	0.84% 1/119	0.00% 0/56	0.00% 0/2
Injury, poisoning and procedural complications Shunt stenosis	0.84% 1/119	0.00% 0/56	0.00% 0/2
Investigations Prostatic specific antigen increased	0.84% 1/119	0.00% 0/56	0.00% 0/2
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/119	1.8% 1/56	0.00% 0/2
Musculoskeletal and connective tissue disorders Mobility decreased	0.00% 0/119	1.8% 1/56	0.00% 0/2
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/119	1.8% 1/56	0.00% 0/2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/119	1.8% 1/56	0.00% 0/2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/119	1.8% 1/56	0.00% 0/2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma benign	0.00% 0/119	1.8% 1/56	0.00% 0/2
Nervous system disorders Basilar artery thrombosis	0.00% 0/119	0.00% 0/56	50.0% 1/2
Nervous system disorders Brain stem stroke	0.00% 0/119	0.00% 0/56	50.0% 1/2
Nervous system disorders Cerebral haemorrhage	0.84% 1/119	0.00% 0/56	0.00% 0/2
Nervous system disorders Dizziness	0.84% 1/119	0.00% 0/56	0.00% 0/2
Nervous system disorders Presyncope	0.84% 1/119	0.00% 0/56	0.00% 0/2
Nervous system disorders Transient ischaemic attack	0.84% 1/119	0.00% 0/56	0.00% 0/2
Renal and urinary disorders Dysuria	0.00% 0/119	1.8% 1/56	0.00% 0/2
Renal and urinary disorders Nephrolithiasis	0.84% 1/119	0.00% 0/56	0.00% 0/2
Renal and urinary disorders Urinary tract obstruction	0.84% 1/119	0.00% 0/56	0.00% 0/2
Reproductive system and breast disorders Benign prostatic hyperplasia	0.84% 1/119	0.00% 0/56	0.00% 0/2
Respiratory, thoracic and mediastinal disorders Atelectasis	0.84% 1/119	0.00% 0/56	0.00% 0/2
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.7% 2/119	0.00% 0/56	0.00% 0/2
Skin and subcutaneous tissue disorders Dermatitis allergic	0.84% 1/119	0.00% 0/56	0.00% 0/2
Vascular disorders Aortic stenosis	0.84% 1/119	0.00% 0/56	0.00% 0/2

Other adverse events

Other adverse events
Measure	Ranibizumab 0.5mg n=119 participants at risk Ranibizumab 0.5mg	Sham With Ranibizumab 0.5mg n=56 participants at risk Sham with Ranibizumab 0.5mg	Sham Without Ranibizumab 0.5mg n=2 participants at risk Sham without Ranibizumab 0.5mg
Eye disorders Conjunctival haemorrhage (Study eye)	9.2% 11/119	12.5% 7/56	0.00% 0/2
Eye disorders Cystoid macular oedema (Study eye)	5.0% 6/119	0.00% 0/56	0.00% 0/2
Eye disorders Dry eye (Study eye)	5.0% 6/119	1.8% 1/56	0.00% 0/2
Eye disorders Eye pain (Study eye)	8.4% 10/119	3.6% 2/56	0.00% 0/2
Eye disorders Macular oedema (Fellow untreated eye)	0.84% 1/119	5.4% 3/56	0.00% 0/2
Eye disorders Macular oedema (Study eye)	5.9% 7/119	3.6% 2/56	0.00% 0/2
Eye disorders Visual acuity reduced (Study eye)	9.2% 11/119	5.4% 3/56	0.00% 0/2
Infections and infestations Influenza	5.0% 6/119	5.4% 3/56	0.00% 0/2
Infections and infestations Nasopharyngitis	10.1% 12/119	3.6% 2/56	0.00% 0/2
Investigations Intraocular pressure increased (Study eye)	5.0% 6/119	5.4% 3/56	0.00% 0/2
Vascular disorders Hypertension	5.0% 6/119	3.6% 2/56	0.00% 0/2

Additional Information

Study Director

Novartis

Phone: 862-778-8300

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER