Trial Outcomes & Findings for Assess the Efficacy/Safety of Intravitreal Ranibizumab in Patients With Vision Loss Due to Choroidal Neovascularization. (NCT NCT01840410)

NCT ID: NCT01840410

Last Updated: 2016-08-26

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. The data were analyzed using mixed model repeated measures (MMRM) which contained scheduled visit, the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate and treatment group by visit and visit by centered baseline BCVA interactions. A positive change from baseline indicated improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 183 participants
• Primary outcome timeframe: Baseline, Month 2
• Results posted on: 2016-08-26

Participant Flow

A total of 183 participants were enrolled. Of these, 178 adults were randomized in a 2:1 ratio and considered for analysis. There were 5 adolescent participants, non-randomized, who received open-label treatment and were not included in the analyses. Therefore, the number enrolled = 183 differs from the participant flow number started = 178.

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 Control 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	119	59
Overall Study Safety Set	119	59
Overall Study Full Analysis Set	119	59
Overall Study COMPLETED	112	55
Overall Study NOT COMPLETED	7	4

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 Control 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	1	2
Overall Study Pregnancy	1	0
Overall Study Protocol deviation	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	2	1
Overall Study Adverse Event	1	1

Baseline Characteristics

Assess the Efficacy/Safety of Intravitreal Ranibizumab in Patients With Vision Loss Due to Choroidal Neovascularization.

Baseline characteristics by cohort

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 Control n=59 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	54.6 Years STANDARD_DEVIATION 15.07 • n=5 Participants	51.9 Years STANDARD_DEVIATION 17.29 • n=7 Participants	53.7 Years STANDARD_DEVIATION 15.85 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	30 Participants n=7 Participants	90 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	29 Participants n=7 Participants	88 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 2

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and Month 2, were analyzed.

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. The data were analyzed using mixed model repeated measures (MMRM) which contained scheduled visit, the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate and treatment group by visit and visit by centered baseline BCVA interactions. A positive change from baseline indicated improvement.

Outcome measures

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 Control n=57 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 to Month 2	9.5 letters Standard Error 0.95	-0.4 letters Standard Error 1.16	—

SECONDARY outcome

Timeframe: Baseline, Month 1, Month 2

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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. The data were analyzed using analysis of covariance (ANCOVA) model which contained the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate. A positive change from baseline indicated improvement.

Outcome measures

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 Control n=57 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	7.1 letters Standard Error 0.75	0.1 letters Standard Error 1.08	—
Change From Baseline in BCVA in Study Eye up to Month 2 Month 2	9.5 letters Standard Error 0.91	-0.4 letters Standard Error 1.31	—

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 participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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

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 Control n=59 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 8 (n=111,55)	-94.7 micrometer (um) Standard Deviation 111.54	-97.9 micrometer (um) Standard Deviation 118.34	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 1 (n=115,56)	-74.4 micrometer (um) Standard Deviation 81.25	3.3 micrometer (um) Standard Deviation 89.43	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 2 (n=114,54)	-76.4 micrometer (um) Standard Deviation 108.24	1.9 micrometer (um) Standard Deviation 119.44	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 3 (n=114,56)	-82.9 micrometer (um) Standard Deviation 114.26	-59.1 micrometer (um) Standard Deviation 142.37	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 4 (n=114,56)	-83.5 micrometer (um) Standard Deviation 104.71	-68.4 micrometer (um) Standard Deviation 155.26	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 5 (n=116,55)	-83.8 micrometer (um) Standard Deviation 112.41	-89.4 micrometer (um) Standard Deviation 130.68	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 6 (n=112,54)	-89.1 micrometer (um) Standard Deviation 109.19	-85.9 micrometer (um) Standard Deviation 117.54	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 7 (n=114,55)	-83.1 micrometer (um) Standard Deviation 105.97	-84.5 micrometer (um) Standard Deviation 141.36	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 9 (n=110,55)	-90.0 micrometer (um) Standard Deviation 112.44	-93.5 micrometer (um) Standard Deviation 113.88	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 10 (n=108,53)	-100.5 micrometer (um) Standard Deviation 119.45	-85.4 micrometer (um) Standard Deviation 136.90	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 11 (n=110,55)	-99.5 micrometer (um) Standard Deviation 112.38	-82.8 micrometer (um) Standard Deviation 158.78	—
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye Month 12 (n=109,55)	-102.7 micrometer (um) Standard Deviation 117.27	-91.7 micrometer (um) Standard Deviation 152.36	—

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 participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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

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 Control n=59 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=115,56)	-0.354 microliter (ul) Standard Deviation 0.4103	0.012 microliter (ul) Standard Deviation 0.3608	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 2 (n=114,54)	-0.357 microliter (ul) Standard Deviation 0.5480	-0.006 microliter (ul) Standard Deviation 0.5792	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 3 (n=114,56)	-0.369 microliter (ul) Standard Deviation 0.5506	-0.269 microliter (ul) Standard Deviation 0.6583	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 4 (n=114,56)	-0.371 microliter (ul) Standard Deviation 0.4798	-0.291 microliter (ul) Standard Deviation 0.7647	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 5 (n=116,55)	-0.392 microliter (ul) Standard Deviation 0.5404	-0.381 microliter (ul) Standard Deviation 0.5750	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 6 (n=112,54)	-0.409 microliter (ul) Standard Deviation 0.5305	-0.375 microliter (ul) Standard Deviation 0.5310	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 7 (n=114,54)	-0.366 microliter (ul) Standard Deviation 0.4905	-0.374 microliter (ul) Standard Deviation 0.5966	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 8 (n=110,55)	-0.414 microliter (ul) Standard Deviation 0.5021	-0.411 microliter (ul) Standard Deviation 0.4970	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 9 (n=110,55)	-0.404 microliter (ul) Standard Deviation 0.5182	-0.413 microliter (ul) Standard Deviation 0.5251	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 10 (n=108,53)	-0.437 microliter (ul) Standard Deviation 0.5506	-0.385 microliter (ul) Standard Deviation 0.5688	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 11 (n=110,55)	-0.448 microliter (ul) Standard Deviation 0.5285	-0.352 microliter (ul) Standard Deviation 0.7021	—
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye Month 12 (n=109,55)	-0.441 microliter (ul) Standard Deviation 0.5460	-0.378 microliter (ul) Standard Deviation 0.6704	—

SECONDARY outcome

Timeframe: Baseline, 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

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 Control n=59 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 Intra-retinal Fluid in Study Eye Compared to Baseline Month 12, Definite (n=111,55)	16 Participants	10 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Baseline, Absent (n=116,56)	70 Participants	32 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Baseline, Definite (n=116,56)	46 Participants	24 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 2, Absent (n=116,56)	97 Participants	29 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 2, Definite (n=116,56)	19 Participants	27 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 6, Absent (n=116,54)	100 Participants	43 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 6, Definite (n=116,54)	16 Participants	11 Participants	—
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline Month 12, Absent (n=111,55)	95 Participants	45 Participants	—

SECONDARY outcome

Timeframe: Baseline, 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.

Presence of subretinal fluid in study eye compared to baseline

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 Control n=59 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 Subretinal Fluid in Study Eye Compared to Baseline Baseline, Absent (n=116,56)	16 Participants	6 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Baseline, Definite (n=116,56)	100 Participants	50 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 2, Absent (n=116,56)	72 Participants	11 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 2, Definite (n=116,56)	44 Participants	45 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 6, Absent (n=116,54)	77 Participants	34 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 6, Definite (n=116,54)	39 Participants	20 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 12, Absent (n=111,55)	78 Participants	41 Participants	—
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline Month 12, Definite (n=111,55)	33 Participants	14 Participants	—

SECONDARY outcome

Timeframe: Baseline, Month 2, Month 6, Month 12

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

The presence of active chorioretinal leakage was assessed by photography imaging, i.e. fluorescein angiography (FA).

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 Control n=59 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 Chorioretinal Leakage Baseline, Absent (n=106,50)	2 Participants	1 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Baseline, Definite (n=106,50)	104 Participants	49 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 2, Absent (n=106,50)	37 Participants	4 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 2, Definite (n=106,50)	69 Participants	46 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 6, Absent (n=108,45)	64 Participants	29 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 6, Definite (n=108,45)	44 Participants	16 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 12, Absent (n=103,47)	81 Participants	37 Participants	—
Number of Participants With Presence of Active Chorioretinal Leakage Month 12, Definite (n=103,47)	22 Participants	10 Participants	—

SECONDARY outcome

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

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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. BCVA was assessed at each month from Month 1 through Month 6 or at each month from Month 1 through month 12, and the data were averaged. The outcome measure is reporting the change between baseline and average BCVA from Month 1 through Month 6 or from Month 1 through Month 12 (average BCVA - baseline BCVA). A positive change from baseline indicated improvement.

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 Control n=59 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	9.53 letters Standard Deviation 10.467	4.68 letters Standard Deviation 8.786	—
Average Change From Baseline in BCVA Average change from BL, month 1 through month 12	9.99 letters Standard Deviation 11.528	6.59 letters Standard Deviation 10.666	—

SECONDARY outcome

Timeframe: Month 2, Month 6, Month 12

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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

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 Control n=59 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,>=15 letters or reaching 84 let.(n=118,57)	37 Participants	7 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, >=10 letters (n=118,57)	50 Participants	8 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, >=1 letter (118,57)	101 Participants	27 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6,>=15 letters or reaching 84 let.(n=118,54)	53 Participants	20 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, >=10 letters (n=118,54)	67 Participants	24 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 2, >=5 letters (n=118,57)	83 Participants	16 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, >= 5 letters (n=118,54)	88 Participants	34 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 6, >= 1 letter (n=118,54)	104 Participants	39 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12,>=15 letters or reaching 84 let.;n=113,55	55 Participants	23 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, >=10 letters (n=113,55)	64 Participants	28 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, >=5 letters (n=113,55)	81 Participants	34 Participants	—
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters Month 12, >=1 letter (n=113,55)	100 Participants	42 Participants	—

SECONDARY outcome

Timeframe: Month 2, Month 6, Month 12

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at both baseline and the given post-baseline time point, were analyzed for that post-baseline time point.

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

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 Control n=59 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 >5 letters (n=118,57)	3 Participants	12 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, loss of >10 letters (n=113,55)	5 Participants	4 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, loss of >1 letter (n=118,57)	10 Participants	24 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, loss of >10 letters (n=118,57)	1 Participants	5 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 2, loss of >15 letters (n=118,57)	1 Participants	3 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, loss of >1 letter (n=118,54)	10 Participants	9 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, loss of >5 letters (n=118,54)	7 Participants	5 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, loss of >10 letters (n=118,54)	6 Participants	2 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 6, loss of >15 letters (n=118,54)	3 Participants	2 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, loss of >1 letter (n=113,55)	9 Participants	10 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12, loss of >5 letters (n=113,55)	6 Participants	6 Participants	—
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss Month 12,loss of >15 letters (n=113,55)	3 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Month 1

Population: The full analysis set (FAS) was considered for the analysis. The FAS included all participants who were randomized to treatment. Only participants, with available data at Month 1, were analyzed.

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

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 Control n=58 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 Requirement for Rescue Treatment at Month 1	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Month 12

Population: Safety set: The safety set included randomized participants who received at least one dose of study treatment and was based on the actual treatment received.

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

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 Control n=52 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=7 Participants Participants did not receive ranibizumab at any time during the study.
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 11	6 Participants	0 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 12	15 Participants	0 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 0	0 Participants	0 Participants	7 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 1	12 Participants	5 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 2	12 Participants	6 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 3	19 Participants	7 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 4	13 Participants	6 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 5	9 Participants	5 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 6	11 Participants	6 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 7	2 Participants	2 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 8	8 Participants	1 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 9	5 Participants	4 Participants	0 Participants
Number of Participants With Ranibizumab Treatments in Study Eye Frequency of injections = 10	7 Participants	10 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12

Population: Safety set: The safety set included randomized participants who received at least one dose of study treatment and was based on the actual treatment received.

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

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 Control n=52 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=7 Participants Participants did not receive ranibizumab at any time during the study.
Number of Participants With Re-treatments Frequency of re-treatment = 1	25 Paticipants	21 Paticipants	0 Paticipants
Number of Participants With Re-treatments Frequency of re-treatment = 2	22 Paticipants	10 Paticipants	0 Paticipants
Number of Participants With Re-treatments Frequency of re-treatment = 3	9 Paticipants	4 Paticipants	0 Paticipants
Number of Participants With Re-treatments Frequency of re-treatment = 4	5 Paticipants	2 Paticipants	0 Paticipants

SECONDARY outcome

Timeframe: Month 12

Population: Safety set: The safety set included randomized participants who received at least one dose of study treatment and was based on the actual treatment received.

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

Measure	Ranibizumab n=580 treatment decisions 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 Control n=328 treatment decisions 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 treatment decisions Participants did not receive ranibizumab at any time during the study.
Number of Primary Reasons for Decision to Treat by Investigator Vision impairment	29 Number of primary reasons	9 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator OCT abnormality	522 Number of primary reasons	306 Number of primary reasons	1 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator FA abnormality	21 Number of primary reasons	13 Number of primary reasons	0 Number of primary reasons
Number of Primary Reasons for Decision to Treat by Investigator Color fundus photography abnormality	1 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	6 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	1 Number of primary reasons	0 Number of primary reasons	0 Number of primary reasons

Adverse Events

Ranibizumab

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Sham With Ranibizumab

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Sham Without Ranibizumab

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ranibizumab n=119 participants at risk 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=52 participants at risk 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 switched to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab n=7 participants at risk Participants did not receive ranibizumab at any time during the study.
Cardiac disorders Atrial fibrillation	0.84% 1/119	0.00% 0/52	0.00% 0/7
Eye disorders Retinal detachment (Fellow untreated eye)	0.84% 1/119	0.00% 0/52	0.00% 0/7
Gastrointestinal disorders Abdominal pain upper	0.84% 1/119	0.00% 0/52	0.00% 0/7
Gastrointestinal disorders Faecaloma	0.00% 0/119	1.9% 1/52	0.00% 0/7
General disorders Pyrexia	0.00% 0/119	1.9% 1/52	0.00% 0/7
Infections and infestations Urosepsis	0.00% 0/119	1.9% 1/52	0.00% 0/7
Musculoskeletal and connective tissue disorders Rheumatic disorder	0.00% 0/119	1.9% 1/52	0.00% 0/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/119	1.9% 1/52	0.00% 0/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papilloma of breast	0.84% 1/119	0.00% 0/52	0.00% 0/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.84% 1/119	0.00% 0/52	0.00% 0/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.84% 1/119	0.00% 0/52	0.00% 0/7
Nervous system disorders Parkinsonism	0.84% 1/119	0.00% 0/52	0.00% 0/7
Renal and urinary disorders Oliguria	0.00% 0/119	1.9% 1/52	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.84% 1/119	0.00% 0/52	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/119	1.9% 1/52	0.00% 0/7
Vascular disorders Peripheral artery stenosis	0.84% 1/119	0.00% 0/52	0.00% 0/7

Other adverse events

Measure	Ranibizumab n=119 participants at risk 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=52 participants at risk 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 switched to open-label ranibizumab on an as needed basis.	Sham Without Ranibizumab n=7 participants at risk Participants did not receive ranibizumab at any time during the study.
Eye disorders Choroidal neovascularisation (Study eye)	2.5% 3/119	0.00% 0/52	14.3% 1/7
Eye disorders Conjunctival haemorrhage (Study eye)	5.9% 7/119	11.5% 6/52	0.00% 0/7
Eye disorders Eye inflammation (Study eye)	0.00% 0/119	0.00% 0/52	14.3% 1/7
Eye disorders Foreign body sensation in eyes (Study eye)	0.84% 1/119	1.9% 1/52	14.3% 1/7
Eye disorders Macular oedema (Study eye)	0.00% 0/119	0.00% 0/52	14.3% 1/7
Eye disorders Ocular hyperaemia (Study eye)	0.84% 1/119	1.9% 1/52	14.3% 1/7
Eye disorders Photopsia (Study eye)	0.84% 1/119	0.00% 0/52	14.3% 1/7
Eye disorders Visual acuity reduced (Study eye)	2.5% 3/119	1.9% 1/52	14.3% 1/7
Infections and infestations Conjunctivitis (Study eye)	1.7% 2/119	5.8% 3/52	0.00% 0/7
Infections and infestations Influenza	7.6% 9/119	0.00% 0/52	0.00% 0/7
Infections and infestations Nasopharyngitis	11.8% 14/119	17.3% 9/52	14.3% 1/7
Infections and infestations Pneumonia	0.84% 1/119	0.00% 0/52	14.3% 1/7
Infections and infestations Sinusitis	1.7% 2/119	5.8% 3/52	0.00% 0/7
Musculoskeletal and connective tissue disorders Back pain	5.0% 6/119	0.00% 0/52	14.3% 1/7
Nervous system disorders Headache	0.84% 1/119	5.8% 3/52	14.3% 1/7
Vascular disorders Hypertension	4.2% 5/119	1.9% 1/52	14.3% 1/7

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