Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. (OLIMPIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02034006
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : February 18, 2019
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Choroidal Neovascularization Secondary to Pathologic Myopia
Intervention Drug: Ranibizumab
Enrollment 200
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Ranibizumab
Hide Arm/Group Description All subjects who received at least one dose of ranibizumab
Period Title: Overall Study
Started 200
Once Treated Patients 70
Re-treated Patients 130
Completed 186
Not Completed 14
Reason Not Completed
Withdrawal by Subject             7
Lost to Follow-up             5
Death             1
Pregnancy             1
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once Total
Hide Arm/Group Description Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Total of all reporting groups
Overall Number of Baseline Participants 70 130 200
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): All subjects who received at least one dose of ranibizumab
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 70 participants 130 participants 200 participants
61.27  (13.03) 62.12  (12.52) 61.82  (12.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 130 participants 200 participants
Female
53
  75.7%
94
  72.3%
147
  73.5%
Male
17
  24.3%
36
  27.7%
53
  26.5%
1.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage
Hide Description 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
Time Frame Screening, Month 2, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent fluorescein angiography at that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Screening: Active leakage, No Number Analyzed 64 participants 124 participants
3 0
Screening: Active leakage, Yes Number Analyzed 64 participants 124 participants
61 121
Screening: Active leakage, NE Number Analyzed 64 participants 124 participants
0 2
Screening: Active leakage, Missing Number Analyzed 64 participants 124 participants
0 1
Month 2: Active leakage, No Number Analyzed 61 participants 119 participants
58 61
Month 2: Active leakage, Yes Number Analyzed 61 participants 119 participants
3 56
Month 2: Active leakage, NE Number Analyzed 61 participants 119 participants
0 2
Month 6: Active leakage, No Number Analyzed 60 participants 115 participants
55 73
Month 6: Active leakage, Yes Number Analyzed 60 participants 115 participants
4 40
Month 6: Active leakage, NE Number Analyzed 60 participants 115 participants
1 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Presence vs. absence of active leakage.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 72.37
Confidence Interval (2-Sided) 95%
23.44 to 223.42
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema
Hide Description 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
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Screening: Macular Edema, No Number Analyzed 69 participants 129 participants
38 63
Screening: Macular Edema, Yes Number Analyzed 69 participants 129 participants
28 65
Screening: Macular Edema, NE Number Analyzed 69 participants 129 participants
3 1
Month 2: Macular Edema, No Number Analyzed 69 participants 129 participants
59 103
Month 2: Macular Edema, Yes Number Analyzed 63 participants 129 participants
3 24
Month 2: Macular Edema, NE Number Analyzed 63 participants 129 participants
1 2
Month 6: Macular Edema, No Number Analyzed 60 participants 126 participants
57 101
Month 6: Macular Edema, Yes Number Analyzed 60 participants 126 participants
2 24
Month 6: Macular Edema, NE Number Analyzed 60 participants 126 participants
1 1
Month 12: Macular Edema, No Number Analyzed 61 participants 124 participants
56 108
Month 12: Macular Edema, Yes Number Analyzed 61 participants 124 participants
4 15
Month 12: Macular Edema, NE Number Analyzed 61 participants 124 participants
1 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Presence vs. absence of macular edema.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.33
Confidence Interval (2-Sided) 95%
3.18 to 27.36
Estimation Comments [Not Specified]
3.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts
Hide Description 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
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Screening: Cysts, No Number Analyzed 69 participants 129 participants
41 79
Screening: Cysts, Yes Number Analyzed 69 participants 129 participants
27 50
Screening: Cysts, NE Number Analyzed 69 participants 129 participants
1 0
Month 2: Cysts, No Number Analyzed 63 participants 129 participants
60 94
Month 2: Cysts, Yes Number Analyzed 63 participants 129 participants
2 32
Month 2: Cysts, NE Number Analyzed 63 participants 129 participants
1 2
Month 2: Cysts, Missing Number Analyzed 63 participants 129 participants
0 1
Month 6: Cysts, No Number Analyzed 60 participants 126 participants
57 98
Month 6: Cysts, Yes Number Analyzed 60 participants 126 participants
2 27
Month 6: Cysts, NE Number Analyzed 60 participants 126 participants
1 1
Month 12: Cysts, No Number Analyzed 61 participants 124 participants
57 97
Month 12: Cysts, Yes Number Analyzed 61 participants 124 participants
3 26
Month 12: Cysts, NE Number Analyzed 61 participants 124 participants
1 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Presence vs. absence of cysts.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 12.66
Confidence Interval (2-Sided) 95%
3.76 to 42.67
Estimation Comments [Not Specified]
4.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid
Hide Description 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
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Screening: Intra-retinal fluid, No Number Analyzed 69 participants 129 participants
19 37
Screening: Intra-retinal fluid, Yes Number Analyzed 69 participants 130 participants
49 90
Screening: Intra-retinal fluid, NE Number Analyzed 69 participants 129 participants
1 2
Month 2: Intra-retinal fluid, No Number Analyzed 63 participants 129 participants
55 77
Month 2: Intra-retinal fluid, Yes Number Analyzed 63 participants 129 participants
7 50
Month 2: Intra-retinal fluid, NE Number Analyzed 63 participants 129 participants
1 2
Month 6: Intra-retinal fluid, No Number Analyzed 60 participants 130 participants
57 85
Month 6: Intra-retinal fluid, Yes Number Analyzed 60 participants 126 participants
1 38
Month 6: Intra-retinal fluid, NE Number Analyzed 60 participants 126 participants
2 3
Month 12: Intra-retinal fluid, No Number Analyzed 61 participants 124 participants
58 96
Month 12: Intra-retinal fluid, Yes Number Analyzed 61 participants 124 participants
2 26
Month 12: Intra-retinal fluid, NE Number Analyzed 61 participants 124 participants
1 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Presence vs. absence of intra-retinal fluid.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 49.80
Confidence Interval (2-Sided) 95%
11.62 to 213.50
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change in Central Subfield Thickness (CSFT)
Hide Description 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.
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point and previous visit.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Mean (Standard Deviation)
Unit of Measure: micromilimeter(um)
Month 2 Vs. Screening : CSFT Number Analyzed 61 participants 125 participants
-16.15  (86.65) -34.28  (78.01)
Month 6 Vs. Month 2: CSFT Number Analyzed 57 participants 121 participants
-11.04  (61.06) -15.83  (70.74)
Month 12 Vs. Month 6: CSFT Number Analyzed 57 participants 119 participants
1.29  (62.55) 8.64  (76.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Change in Central subfield thickness vs previous visit.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1514
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.99 to 1.00
Estimation Comments [Not Specified]
6.Primary Outcome
Title Change in Central Subfield Volume (CSV)
Hide Description 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.
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Mean (Standard Deviation)
Unit of Measure: mm^3
Month 2 Vs. Screening : CSV Number Analyzed 49 participants 96 participants
-0.02  (0.06) -0.02  (0.06)
Month 6 Vs. Month 2: CSV Number Analyzed 48 participants 97 participants
-0.00  (0.04) -0.01  (0.07)
Month 12 Vs. Month 6: CSV Number Analyzed 49 participants 101 participants
-0.00  (0.04) 0.01  (0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Change in Central subfield volume vs previous visit.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1265
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 5.63
Estimation Comments [Not Specified]
7.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid
Hide Description 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
Time Frame Screening, Month 2, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent OCT at that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Screening: Sub-retinal fluid, No Number Analyzed 69 participants 129 participants
43 65
Screening: Sub-retinal fluid, Yes Number Analyzed 69 participants 129 participants
25 61
Screening: Sub-retinal fluid, NE Number Analyzed 69 participants 129 participants
1 3
Month 2: Sub-retinal fluid, No Number Analyzed 63 participants 130 participants
58 108
Month 2: Sub-retinal fluid, Yes Number Analyzed 63 participants 129 participants
2 17
Month 2: Sub-retinal fluid, NE Number Analyzed 63 participants 129 participants
3 4
Month 6: Sub-retinal fluid, No Number Analyzed 60 participants 126 participants
58 109
Month 6: Sub-retinal fluid, Yes Number Analyzed 60 participants 126 participants
0 14
Month 6: Sub-retinal fluid, NE Number Analyzed 60 participants 126 participants
2 3
Month 12: Sub-retinal fluid, No Number Analyzed 61 participants 124 participants
60 113
Month 12: Sub-retinal fluid, Yes Number Analyzed 61 participants 124 participants
0 8
Month 12: Sub-retinal fluid, NE Number Analyzed 61 participants 124 participants
1 3
8.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities
Hide Description 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.
Time Frame Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and underwent ocular examination during that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Baseline: Clinically Significant Abnormal, No 61 103
Baseline: Clinically Significant Abnormal, Yes 9 27
Baseline: Clinically Significant Abnormal, Missing 0 0
Month 1: Clinically Significant Abnorma, No 60 106
Month 1: Clinically Significant Abnormal, Yes 6 24
Month 1: Clinically Significant Abnormal, Missing 4 0
Month 2: Clinically Significant Abnormal, No 60 103
Month 2: Clinically Significant Abnormal, Yes 5 26
Month 2:Clinically Significant Abnormal, Missing 5 1
Month 3: Clinically Significant Abnormal, No 56 108
Month 3: Clinically Significant Abnormal, Yes 7 20
Month 3: Clinically Significant Abnormal, Missing 7 2
Month 6: Clinically Significant Abnormal, No 59 110
Month 6: Clinically Significant Abnormal, Yes 3 18
Month 6: Clinically Significant Abnormal, Missing 8 2
Month 12: Clinically Significant Abnormal, No 61 116
Month 12: Clinically Significant Abnormal, Yes 2 12
Month 12: Clinically Significant Abnormal, Missing 7 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Presence vs. absence of clinically significant abnormalities.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0103
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.91
Confidence Interval (2-Sided) 95%
1.58 to 30.23
Estimation Comments [Not Specified]
9.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters
Hide Description 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.
Time Frame Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Month 1: Gain >= 5 letters Number Analyzed 51 participants 97 participants
37 69
Month 1: Gain < 5 letters Number Analyzed 51 participants 97 participants
14 28
Month 2: Gain >= 5 letters Number Analyzed 50 participants 95 participants
38 70
Month 2: Gain < 5 letters Number Analyzed 50 participants 95 participants
12 25
Month 3: Gain >= 5 letters Number Analyzed 52 participants 94 participants
37 74
Month 3: Gain < 5 letters Number Analyzed 52 participants 94 participants
15 20
Month 6: Gain >= 5 letters Number Analyzed 48 participants 92 participants
40 70
Month 6: Gain < 5 letters Number Analyzed 48 participants 92 participants
8 22
Month 12: Gain >= 5 letters Number Analyzed 51 participants 92 participants
43 69
Month 12: Gain < 5 letters Number Analyzed 51 participants 92 participants
8 23
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Gain < 5 letters vs. Gain >= 5 letters.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0854
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
0.90 to 5.33
Estimation Comments [Not Specified]
10.Primary Outcome
Title Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters
Hide Description 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.
Time Frame Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Month 1: Gain >= 10 letters Number Analyzed 51 participants 97 participants
13 27
Month 1: Gain < 10 letters Number Analyzed 51 participants 97 participants
38 70
Month 2: Gain >= 10 letters Number Analyzed 50 participants 95 participants
20 40
Month 2: Gain < 10 letters Number Analyzed 50 participants 95 participants
30 55
Month 3: Gain >= 10 letters Number Analyzed 52 participants 94 participants
22 41
Month 3: Gain < 10 letters Number Analyzed 52 participants 94 participants
30 53
Month 6: Gain >= 10 letters Number Analyzed 48 participants 92 participants
29 50
Month 6: Gain < 10 letters Number Analyzed 48 participants 92 participants
19 42
Month 12: Gain >= 10 letters Number Analyzed 51 participants 92 participants
28 48
Month 12: Gain < 10 letters Number Analyzed 51 participants 92 participants
23 44
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Gain < 10 letters vs. Gain >= 10 letters.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0114
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.52
Confidence Interval (2-Sided) 95%
1.23 to 5.17
Estimation Comments [Not Specified]
11.Primary Outcome
Title Number of Patients in Different Categories of Changes From Baseline in BCVA
Hide Description 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.
Time Frame Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab and evaluable BCVA at baseline and that time point.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Measure Type: Number
Unit of Measure: Patients
Month 1: No change Number Analyzed 66 participants 130 participants
7 18
Month 1: Worsening Number Analyzed 66 participants 130 participants
8 15
Month 1: Improvement Number Analyzed 66 participants 130 participants
51 97
Month 2: No change Number Analyzed 65 participants 129 participants
6 9
Month 2: Worsening Number Analyzed 65 participants 129 participants
9 25
Month 2: Improvement Number Analyzed 65 participants 129 participants
50 95
Month 3: No change Number Analyzed 63 participants 128 participants
3 9
Month 3: Worsening Number Analyzed 63 participants 128 participants
8 25
Month 3: Improvement Number Analyzed 63 participants 128 participants
52 94
Month 6: No change Number Analyzed 62 participants 128 participants
5 6
Month 6: Worsening Number Analyzed 62 participants 128 participants
9 30
Month 6: Improvement Number Analyzed 62 participants 128 participants
48 92
Month 12: No change Number Analyzed 63 participants 128 participants
3 7
Month 12: Worsening Number Analyzed 63 participants 128 participants
9 29
Month 12: Improvement Number Analyzed 63 participants 128 participants
51 92
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Change from baseline in BCVA: Improved vs. No change. For retreated subjects, the last scheduled assessment prior to the first retreatment was considered. For subjects treated only once, the last scheduled assessment available was considered.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.25 to 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab: Treated Once, Ranibizumab: Re-treated Once
Comments Change from baseline in BCVA: Worsened vs. No change
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0461
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.53
Confidence Interval (2-Sided) 95%
0.69 to 44.52
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye
Hide Description 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.
Time Frame Baseline, Month 6, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab
Hide Arm/Group Description:
Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.
Overall Number of Participants Analyzed 200
Overall Number of Units Analyzed
Type of Units Analyzed: Study eyes
200
Mean (Standard Deviation)
Unit of Measure: letters
Change at 6 month Number Analyzed 190 study eyes
7.51  (11.68)
Change at 12 month Number Analyzed 191 study eyes
8.42  (12.81)
13.Secondary Outcome
Title Mean Number of Ranibizumab Injection
Hide Description Mean number of ranibizumab injection is reported as number of injections per patient.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab
Arm/Group Title Ranibizumab
Hide Arm/Group Description:
Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.
Overall Number of Participants Analyzed 200
Mean (Standard Deviation)
Unit of Measure: injections
2.41  (1.53)
14.Secondary Outcome
Title Time to Re-treatment
Hide Description 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.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab
Arm/Group Title Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 130
Mean (Standard Deviation)
Unit of Measure: Months
2.56  (2.17)
15.Secondary Outcome
Title Number of Patients Having Ocular and/or Systemic Adverse Event (AE)
Hide Description Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
Arm/Group Title Ranibizumab
Hide Arm/Group Description:
Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.
Overall Number of Participants Analyzed 200
Measure Type: Number
Unit of Measure: Patients
Any systemic Adverse Event 30
Serious systemic Adverse Event 5
Ocular Adverse Event 41
Ocular serious adverse event 2
16.Secondary Outcome
Title Change in Patient Quality of Life From Baseline to Month 2 and Month 12
Hide Description 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
Time Frame Baseline, Month 2, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab with data at both timepoints.
Arm/Group Title Ranibizumab: Treated Once Ranibizumab: Re-treated Once
Hide Arm/Group Description:
Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.
Overall Number of Participants Analyzed 70 130
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change at Month 2 Number Analyzed 60 participants 124 participants
-0.40  (0.68) -0.15  (0.60)
Change at month 12 Number Analyzed 59 participants 122 participants
-0.54  (0.91) -0.36  (0.81)
Time Frame Adverse events were collected from time of treatment until exit from the study (approximately 12 months)
Adverse Event Reporting Description Safety Population: All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
 
Arm/Group Title Ranibizumab
Hide Arm/Group Description All subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment.
All-Cause Mortality
Ranibizumab
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Ranibizumab
Affected / at Risk (%)
Total   7/200 (3.50%) 
Cardiac disorders   
Atrioventricular block  1  1/200 (0.50%) 
Cardiac arrest  1  1/200 (0.50%) 
Hepatobiliary disorders   
Cholecystitis acute  1  1/200 (0.50%) 
Infections and infestations   
Klebsiella sepsis  1  1/200 (0.50%) 
Injury, poisoning and procedural complications   
Expired product administered (Study Eye)  1  2/200 (1.00%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/200 (0.50%) 
Reproductive system and breast disorders   
Ovarian cyst  1  1/200 (0.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Ranibizumab
Affected / at Risk (%)
Total   26/200 (13.00%) 
Eye disorders   
Choroidal neovascularisation (Non-study Eye)  1  3/200 (1.50%) 
Choroidal neovascularisation (Study Eye)  1  7/200 (3.50%) 
Conjunctival haemorrhage (Study Eye)  1  4/200 (2.00%) 
Conjunctival hyperaemia (Both Eyes)  1  5/200 (2.50%) 
Ocular hypertension (Both Eyes)  1  4/200 (2.00%) 
Infections and infestations   
Influenza  1  7/200 (3.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02034006    
Other Study ID Numbers: CRFB002FIT01
2013-003334-33 ( EudraCT Number )
First Submitted: January 9, 2014
First Posted: January 13, 2014
Results First Submitted: July 11, 2017
Results First Posted: February 18, 2019
Last Update Posted: February 18, 2019