Trial Outcomes & Findings for A Study of the Criteria Establishing the Need for Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia. (NCT NCT02034006)

NCT ID: NCT02034006

Last Updated: 2019-02-18

Results Overview

Presence of active leakage on fluorescein angiography (FAG) was assessed at screening (14 to 3 days before baseline visit), month 2 and month 6. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of active leakage (Yes/No). For retreated patients, the presence/absence of active leakage was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 200 participants
• Primary outcome timeframe: Screening, Month 2, Month 6
• Results posted on: 2019-02-18

Participant Flow

Two hundred fifteen (215) subjects were screened in this study (i.e. provided written informed consent). Two hundred (200) subjects underwent baseline visit and received at least one injection of ranibizumab.

Participant milestones

Measure	Ranibizumab All subjects who received at least one dose of ranibizumab
Overall Study STARTED	200
Overall Study Once Treated Patients	70
Overall Study Re-treated Patients	130
Overall Study COMPLETED	186
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Measure	Ranibizumab All subjects who received at least one dose of ranibizumab
Overall Study Withdrawal by Subject	7
Overall Study Lost to Follow-up	5
Overall Study Death	1
Overall Study Pregnancy	1

Baseline Characteristics

A Study of the Criteria Establishing the Need for Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia.

Baseline characteristics by cohort

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Total n=200 Participants Total of all reporting groups
Age, Continuous	61.27 Years STANDARD_DEVIATION 13.03 • n=5 Participants	62.12 Years STANDARD_DEVIATION 12.52 • n=7 Participants	61.82 Years STANDARD_DEVIATION 12.67 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	94 Participants n=7 Participants	147 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	36 Participants n=7 Participants	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent fluorescein angiography at that time point.

Presence of active leakage on fluorescein angiography (FAG) was assessed at screening (14 to 3 days before baseline visit), month 2 and month 6. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of active leakage (Yes/No). For retreated patients, the presence/absence of active leakage was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 6: Active leakage, Yes	4 Patients	40 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Screening: Active leakage, No	3 Patients	0 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Screening: Active leakage, Yes	61 Patients	121 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Screening: Active leakage, NE	0 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Screening: Active leakage, Missing	0 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 2: Active leakage, No	58 Patients	61 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 2: Active leakage, Yes	3 Patients	56 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 2: Active leakage, NE	0 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 6: Active leakage, No	55 Patients	73 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage Month 6: Active leakage, NE	1 Patients	2 Patients

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.

Presence of macular edema from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of macular edema (Yes/No). For retreated patients, the presence/absence of macular edema was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Screening: Macular Edema, No	38 Patients	63 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Screening: Macular Edema, Yes	28 Patients	65 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Screening: Macular Edema, NE	3 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 2: Macular Edema, No	59 Patients	103 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 2: Macular Edema, Yes	3 Patients	24 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 2: Macular Edema, NE	1 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 6: Macular Edema, No	57 Patients	101 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 6: Macular Edema, Yes	2 Patients	24 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 6: Macular Edema, NE	1 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 12: Macular Edema, No	56 Patients	108 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 12: Macular Edema, Yes	4 Patients	15 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema Month 12: Macular Edema, NE	1 Patients	1 Patients

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.

Presence of cysts from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of cysts (Yes/No). For retreated patients, the presence/absence of cysts was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Screening: Cysts, No	41 Patients	79 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Screening: Cysts, Yes	27 Patients	50 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Screening: Cysts, NE	1 Patients	0 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 2: Cysts, No	60 Patients	94 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 2: Cysts, Yes	2 Patients	32 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 2: Cysts, NE	1 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 2: Cysts, Missing	0 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 6: Cysts, No	57 Patients	98 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 6: Cysts, Yes	2 Patients	27 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 6: Cysts, NE	1 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 12: Cysts, No	57 Patients	97 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 12: Cysts, Yes	3 Patients	26 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts Month 12: Cysts, NE	1 Patients	1 Patients

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.

Presence of Intra-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of Intra-retinal fluid (Yes/No). For retreated patients, the presence/absence of Intra-retinal fluid was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Screening: Intra-retinal fluid, No	19 Patients	37 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Screening: Intra-retinal fluid, Yes	49 Patients	90 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Screening: Intra-retinal fluid, NE	1 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 2: Intra-retinal fluid, No	55 Patients	77 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 2: Intra-retinal fluid, Yes	7 Patients	50 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 2: Intra-retinal fluid, NE	1 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 6: Intra-retinal fluid, No	57 Patients	85 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 6: Intra-retinal fluid, Yes	1 Patients	38 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 6: Intra-retinal fluid, NE	2 Patients	3 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 12: Intra-retinal fluid, No	58 Patients	96 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 12: Intra-retinal fluid, Yes	2 Patients	26 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid Month 12: Intra-retinal fluid, NE	1 Patients	2 Patients

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point and previous visit.

Central subfield thickness (CSFT) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSFT versus previous visit. For retreated patients, the change in CSFT was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Change in Central Subfield Thickness (CSFT) Month 2 Vs. Screening : CSFT	-16.15 micromilimeter(um) Standard Deviation 86.65	-34.28 micromilimeter(um) Standard Deviation 78.01
Change in Central Subfield Thickness (CSFT) Month 6 Vs. Month 2: CSFT	-11.04 micromilimeter(um) Standard Deviation 61.06	-15.83 micromilimeter(um) Standard Deviation 70.74
Change in Central Subfield Thickness (CSFT) Month 12 Vs. Month 6: CSFT	1.29 micromilimeter(um) Standard Deviation 62.55	8.64 micromilimeter(um) Standard Deviation 76.79

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point and the previous visit.

Central subfield volume (CSV) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSV versus previous visit. For retreated patients, the change in CSV was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Change in Central Subfield Volume (CSV) Month 2 Vs. Screening : CSV	-0.02 mm^3 Standard Deviation 0.06	-0.02 mm^3 Standard Deviation 0.06
Change in Central Subfield Volume (CSV) Month 6 Vs. Month 2: CSV	-0.00 mm^3 Standard Deviation 0.04	-0.01 mm^3 Standard Deviation 0.07
Change in Central Subfield Volume (CSV) Month 12 Vs. Month 6: CSV	-0.00 mm^3 Standard Deviation 0.04	0.01 mm^3 Standard Deviation 0.08

PRIMARY outcome

Timeframe: Screening, Month 2, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.

Presence of sub-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. The regression model for sub-retinal fluid was not valid because "Yes" was reported in almost all subjects causing a quasi-complete separation of data points. *NE = Not evaluable

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 12: Sub-retinal fluid, Yes	0 Patients	8 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Screening: Sub-retinal fluid, No	43 Patients	65 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Screening: Sub-retinal fluid, Yes	25 Patients	61 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Screening: Sub-retinal fluid, NE	1 Patients	3 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 2: Sub-retinal fluid, No	58 Patients	108 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 2: Sub-retinal fluid, Yes	2 Patients	17 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 2: Sub-retinal fluid, NE	3 Patients	4 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 6: Sub-retinal fluid, No	58 Patients	109 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 6: Sub-retinal fluid, Yes	0 Patients	14 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 6: Sub-retinal fluid, NE	2 Patients	3 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 12: Sub-retinal fluid, No	60 Patients	113 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid Month 12: Sub-retinal fluid, NE	1 Patients	3 Patients

PRIMARY outcome

Timeframe: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent ocular examination during that time point.

Presence of clinically significant abnormalities was assessed at baseline, month 1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of clinically significant abnormalities (Yes/No). For retreated patients, the presence/absence of clinically significant abnormalities was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Baseline: Clinically Significant Abnormal, No	61 Patients	103 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Baseline: Clinically Significant Abnormal, Yes	9 Patients	27 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Baseline: Clinically Significant Abnormal, Missing	0 Patients	0 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 1: Clinically Significant Abnorma, No	60 Patients	106 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 1: Clinically Significant Abnormal, Yes	6 Patients	24 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 1: Clinically Significant Abnormal, Missing	4 Patients	0 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 2: Clinically Significant Abnormal, No	60 Patients	103 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 2: Clinically Significant Abnormal, Yes	5 Patients	26 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 2:Clinically Significant Abnormal, Missing	5 Patients	1 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 3: Clinically Significant Abnormal, No	56 Patients	108 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 3: Clinically Significant Abnormal, Yes	7 Patients	20 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 3: Clinically Significant Abnormal, Missing	7 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 6: Clinically Significant Abnormal, No	59 Patients	110 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 6: Clinically Significant Abnormal, Yes	3 Patients	18 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 6: Clinically Significant Abnormal, Missing	8 Patients	2 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 12: Clinically Significant Abnormal, No	61 Patients	116 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 12: Clinically Significant Abnormal, Yes	2 Patients	12 Patients
Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities Month 12: Clinically Significant Abnormal, Missing	7 Patients	2 Patients

PRIMARY outcome

Timeframe: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab with improvement in BCVA \< 5 letters from baseline at that time point.

Improvement in BCVA < 5 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA < 5 letters (Yes/No) which was reported as Gain >= 5 letters versus Gain < 5 letters. For retreated patients, Gain >= 5 letters and Gain < 5 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 1: Gain >= 5 letters	37 Patients	69 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 1: Gain < 5 letters	14 Patients	28 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 2: Gain >= 5 letters	38 Patients	70 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 2: Gain < 5 letters	12 Patients	25 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 3: Gain >= 5 letters	37 Patients	74 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 3: Gain < 5 letters	15 Patients	20 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 6: Gain >= 5 letters	40 Patients	70 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 6: Gain < 5 letters	8 Patients	22 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 12: Gain >= 5 letters	43 Patients	69 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters Month 12: Gain < 5 letters	8 Patients	23 Patients

PRIMARY outcome

Timeframe: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab with improvement in BCVA \< 10 letters from baseline to that time point.

Improvement in BCVA < 10 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA < 10 letters (Yes/No) which was reported as Gain >= 10 letters versus Gain < 10 letters. For retreated patients, Gain >= 10 letters and Gain < 10 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 1: Gain >= 10 letters	13 Patients	27 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 1: Gain < 10 letters	38 Patients	70 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 2: Gain >= 10 letters	20 Patients	40 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 2: Gain < 10 letters	30 Patients	55 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 3: Gain >= 10 letters	22 Patients	41 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 3: Gain < 10 letters	30 Patients	53 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 6: Gain >= 10 letters	29 Patients	50 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 6: Gain < 10 letters	19 Patients	42 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 12: Gain >= 10 letters	28 Patients	48 Patients
Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters Month 12: Gain < 10 letters	23 Patients	44 Patients

PRIMARY outcome

Timeframe: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and evaluable BCVA at baseline and that time point.

Changes from baseline in BCVA are described for the ETDRS parameter considering the following categories at each assessment: "no change" if the change was equal to 0 letter, "worsening" if change < 0 letter , "improvement" if change > 0 letter. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change from baseline in BCVA (improved/worsened/stable) which was reported as Improved versus no change and worsened versus no change. For retreated patients, this variable was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 1: No change	7 Patients	18 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 1: Worsening	8 Patients	15 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 1: Improvement	51 Patients	97 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 2: No change	6 Patients	9 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 2: Worsening	9 Patients	25 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 2: Improvement	50 Patients	95 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 3: No change	3 Patients	9 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 3: Worsening	8 Patients	25 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 3: Improvement	52 Patients	94 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 6: No change	5 Patients	6 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 6: Worsening	9 Patients	30 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 6: Improvement	48 Patients	92 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 12: No change	3 Patients	7 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 12: Worsening	9 Patients	29 Patients
Number of Patients in Different Categories of Changes From Baseline in BCVA Month 12: Improvement	51 Patients	92 Patients

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. The study eyes of the patients belonging to the FAS were analyzed.

Change from baseline in BCVA (Best Corrected Visual Acuity) was Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. Patients with a BCVA ETDRS letter score of 78 to 24 in the study eye were included; A higher score represents better functioning of the study eye. A positive change from baseline shows improvement.

Outcome measures

Measure	Ranibizumab: Treated Once n=200 study eyes Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye Change at 6 month	7.51 letters Standard Deviation 11.68	—
Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye Change at 12 month	8.42 letters Standard Deviation 12.81	—

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab

Mean number of ranibizumab injection is reported as number of injections per patient.

Outcome measures

Measure	Ranibizumab: Treated Once n=200 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Mean Number of Ranibizumab Injection	2.41 injections Standard Deviation 1.53	—

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab

Time to re-treatment, defined as time in months from the data of first dose of ranibizumab to the date of re-treatment, was evaluated.

Outcome measures

Measure	Ranibizumab: Treated Once n=130 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Time to Re-treatment	2.56 Months Standard Deviation 2.17	—

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Safety Population: all subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported

Outcome measures

Measure	Ranibizumab: Treated Once n=200 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Number of Patients Having Ocular and/or Systemic Adverse Event (AE) Any systemic Adverse Event	30 Patients	—
Number of Patients Having Ocular and/or Systemic Adverse Event (AE) Serious systemic Adverse Event	5 Patients	—
Number of Patients Having Ocular and/or Systemic Adverse Event (AE) Ocular Adverse Event	41 Patients	—
Number of Patients Having Ocular and/or Systemic Adverse Event (AE) Ocular serious adverse event	2 Patients	—

SECONDARY outcome

Timeframe: Baseline, Month 2, Month 12

Population: Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab with data at both timepoints.

Patient quality of life was assessed by Impact of Vision Impairment (IVI) questionnaire. IVI is a 32-item instrument, either self- or interviewer-administered, developed to measure the impact of vision impairment on daily activities in five domains. The 32 items were divided into 5 domains as follows: Leisure and work (items 1 to 5), Social and consumer interaction (items 6 to 10 and items 23-24), Household and personal care (items 11 to 14 and items 20-21), Mobility (items 15 to 19 and item 22), Emotional reaction to vision loss (items 25 to 32). Responses to the IVI items were rated on a five-category Likert scale: not at all, 0; hardly at all, 1; a little, 2; a fair amount, 3; a lot, 4; and can't do because of eyesight, 5. Total score was an arithmetic average of the items rated between 0 (the best score) and 5 (the worst score). A negative change indicates improvement. Data was computed on items with non missing response

Outcome measures

Measure	Ranibizumab: Treated Once n=70 Participants Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.	Ranibizumab: Re-treated Once n=130 Participants Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Change in Patient Quality of Life From Baseline to Month 2 and Month 12 Change at Month 2	-0.40 units on a scale Standard Deviation 0.68	-0.15 units on a scale Standard Deviation 0.60
Change in Patient Quality of Life From Baseline to Month 2 and Month 12 Change at month 12	-0.54 units on a scale Standard Deviation 0.91	-0.36 units on a scale Standard Deviation 0.81

Adverse Events

Ranibizumab

Serious events: 7 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ranibizumab n=200 participants at risk All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Cardiac disorders Atrioventricular block	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Cardiac disorders Cardiac arrest	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Hepatobiliary disorders Cholecystitis acute	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Infections and infestations Klebsiella sepsis	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Injury, poisoning and procedural complications Expired product administered (Study Eye)	1.0% 2/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Reproductive system and breast disorders Ovarian cyst	0.50% 1/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

Other adverse events

Measure	Ranibizumab n=200 participants at risk All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Eye disorders Choroidal neovascularisation (Non-study Eye)	1.5% 3/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Eye disorders Choroidal neovascularisation (Study Eye)	3.5% 7/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Eye disorders Conjunctival haemorrhage (Study Eye)	2.0% 4/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Eye disorders Conjunctival hyperaemia (Both Eyes)	2.5% 5/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Eye disorders Ocular hypertension (Both Eyes)	2.0% 4/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Infections and infestations Influenza	3.5% 7/200 • Adverse events were collected from time of treatment until exit from the study (approximately 12 months) Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.

Additional Information

Study Director

Novartis Pharmaceuticals

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