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)

• 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: Novartis Pharmaceuticals
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Ranibizumab: Treated Once	Ranibizumab: Re-treated Once	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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)
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

Outcome Measure Data

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
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)

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)
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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
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

Outcome Measure Data

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
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

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]

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
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

Outcome Measure Data

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
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
Description	Mean number of ranibizumab injection is reported as number of injections per patient.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ranibizumab
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
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ranibizumab: Re-treated Once
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)
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)

Adverse Events

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
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	--/--
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)
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)

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ricci F, Staurenghi G, Varano M, Eandi C, Sinibaldi TL, Colombo L, Bartezaghi M, Bassanini S. OLIMPIC: a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):759-768. doi: 10.1007/s00417-019-04248-8. Epub 2019 Jan 24.

• 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