Trial Outcomes & Findings for Efficacy and Safety of Ranibizumab in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia (NCT NCT01217944)

Last Updated: 2014-02-10

Results Overview

The Best Corrected Visual Acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts at baseline and compared to the average from month 1 to month 3.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

277 participants

Primary outcome timeframe

Baseline, Month 1 through Month 3

Results posted on

2014-02-10

Participant Flow

Out of the 334 patients screened, 277 patients were randomized into the study on a 2:2:1 basis: 106 patients to Group I (treatment with ranibizumab according to visual acuity stabilization), 116 patients to Group II (ranibizumab treatment according to disease activity), and 55 patients to Group III (treatment with vPDT)

Participant milestones

Participant milestones
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Overall Study STARTED	106	116	55
Overall Study Completed 3 Months	105	116	55
Overall Study Completed 6 Months	103	116	55
Overall Study COMPLETED	100	112	55
Overall Study NOT COMPLETED	6	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria
Overall Study Protocol Violation	1	1
Overall Study Lost to Follow-up	3	1
Overall Study Withdrawal by Subject	1	2
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

Efficacy and Safety of Ranibizumab in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=106 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.	Total n=277 Participants Total of all reporting groups
Age, Customized <45 years	24 Participants 22.6 • n=5 Participants	24 Participants 20.7 • n=7 Participants	7 Participants 12.7 • n=5 Participants	55 Participants n=4 Participants
Age, Customized 45 -< 55 years	27 Participants n=5 Participants	21 Participants n=7 Participants	16 Participants n=5 Participants	64 Participants n=4 Participants
Age, Customized 55-<65 years	30 Participants n=5 Participants	34 Participants n=7 Participants	14 Participants n=5 Participants	78 Participants n=4 Participants
Age, Customized >=65	25 Participants n=5 Participants	37 Participants n=7 Participants	18 Participants n=5 Participants	80 Participants n=4 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	87 Participants n=7 Participants	40 Participants n=5 Participants	209 Participants n=4 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	29 Participants n=7 Participants	15 Participants n=5 Participants	68 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Month 1 through Month 3

Population: Participants from the Full Analysis Set, included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Average Change From Baseline to Month 1 Through Month 3 on Visual Acuity of the Study Eye Baseline	55.4 Letters Standard Deviation 13.43	55.8 Letters Standard Deviation 12.59	54.7 Letters Standard Deviation 13.84
Average Change From Baseline to Month 1 Through Month 3 on Visual Acuity of the Study Eye Average Month 1 to month 3	66.0 Letters Standard Deviation 12.98	66.4 Letters Standard Deviation 12.28	56.9 Letters Standard Deviation 14.49

SECONDARY outcome

Timeframe: Baseline and Month 6

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Average Change From Baseline to Month 6 in Visual Acuity of the Study Eye Baseline	55.4 Letters Standard Deviation 13.43	55.8 Letters Standard Deviation 12.59	54.7 Letters Standard Deviation 13.84
Average Change From Baseline to Month 6 in Visual Acuity of the Study Eye Average month 1 to month 6	69.2 Letters Standard Deviation 12.44	68.4 Letters Standard Deviation 13.56	62.7 Letters Standard Deviation 14.65

SECONDARY outcome

Timeframe: Baseline and Month 1 through Month 12

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Average Change From Baseline to Month 1 Through Month 12 in Visual Acuity of the Study Eye Baseline	55.4 Letters Standard Deviation 13.43	55.8 Letters Standard Deviation 12.59	54.7 Letters Standard Deviation 13.84
Average Change From Baseline to Month 1 Through Month 12 in Visual Acuity of the Study Eye Average Month 1 to Month 12	68.3 Letters Standard Deviation 12.61	68.3 Letters Standard Deviation 12.45	61.1 Letters Standard Deviation 14.86

SECONDARY outcome

Timeframe: Month 3

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained more than 10 or more than 15 of visual acuity at month 3.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 3 Month 3 >=15 letters	38.1 Percentage of Patients	43.1 Percentage of Patients	14.5 Percentage of Patients
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 3 Month 3 >= 10 letters	61.9 Percentage of Patients	65.5 Percentage of Patients	27.3 Percentage of Patients

SECONDARY outcome

Timeframe: Months 6 and 12

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained more than 10 or more than 15 letters of visual acuity at month 6 and month 12.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 6 and Month 12 Month 6 >=15 letters	46.7 Percentage of Patients	44.8 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 6 and Month 12 Month 6 >= 10 letters	71.4 Percentage of Patients	64.7 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 6 and Month 12 Month 12 >=15 letters	53.3 Percentage of Patients	51.7 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 6 and Month 12 Month 12 >= 10 letters	69.5 Percentage of Patients	69.0 Percentage of Patients	—

SECONDARY outcome

Timeframe: Month 3

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. A decreased score indicates worsening in acuity. This outcome assessed the percentage of participants who lost more than 10 or more than 15 of visual acuity at month 3.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 3 Month 3 >=10 letters	1.9 Percentage of Patients	0.9 Percentage of Patients	16.4 Percentage of Patients
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 3 Month 3 >= 15 letters	1.9 Percentage of Patients	0 Percentage of Patients	7.4 Percentage of Patients

SECONDARY outcome

Timeframe: Months 6 and 12

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. A decreased score indicates worsening in acuity. This outcome assessed the percentage of participants who lost more than 10 or more than 15 of visual acuity at month 6 and 12.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 6 and 12 Month 6 >=10 letters	1.9 Percentage of Patients	2.6 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 6 and 12 Month 6 >= 15 letters	0 Percentage of Patients	0.9 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 6 and 12 Month 12 >=10 letters	4.8 Percentage of Patients	1.7 Percentage of Patients	—
Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 6 and 12 Month 12 >= 15 letters	1.9 Percentage of Patients	0.9 Percentage of Patients	—

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6 and Month 12

Retinal thickness was measured by Central Reading Center using patient's Optical Coherence Tomography (OCT) images provided by investigators.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=102 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=110 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Change From Baseline in Central Retinal Thickness of the Study Eye Over Time Baseline (n=102,110, 54)	349.2 Microns Standard Deviation 95.05	373.1 Microns Standard Deviation 127.44	352.5 Microns Standard Deviation 101.52
Change From Baseline in Central Retinal Thickness of the Study Eye Over Time Month 3 (n= 102,110,54)	288.3 Microns Standard Deviation 70.14	295.6 Microns Standard Deviation 71.93	340.5 Microns Standard Deviation 106.03
Change From Baseline in Central Retinal Thickness of the Study Eye Over Time Month 6 (n= 102,110,55)	283.1 Microns Standard Deviation 67.43	298.3 Microns Standard Deviation 81.16	303.5 Microns Standard Deviation 76.81
Change From Baseline in Central Retinal Thickness of the Study Eye Over Time Month 12 (n= 102,110,55)	282.6 Microns Standard Deviation 68.62	301.8 Microns Standard Deviation 88.16	294.3 Microns Standard Deviation 83.25

SECONDARY outcome

Timeframe: Baseline and Month 12

CNV leakage assessment plus other choroid and retinal disorders were assessed by Central Reading Center using patient's fluorescein angiography and color fundus photography images provided by investigators.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=105 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=116 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=55 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Baseline-Definite	96.2 Percentage of Patients	93.1 Percentage of Patients	100.0 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Baseline- Questionable	1.0 Percentage of Patients	0.0 Percentage of Patients	0.0 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Baseline-Absent	1.0 Percentage of Patients	0.9 Percentage of Patients	0.0 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Baseline- Other	1.9 Percentage of Patients	6.1 Percentage of Patients	0.0 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Month 12-Definite	21.0 Percentage of Patients	19.0 Percentage of Patients	29.1 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Month 12- Questionable	0.0 Percentage of Patients	0.0 Percentage of Patients	1.8 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Month 12-Absent	68.6 Percentage of Patients	69.8 Percentage of Patients	65.5 Percentage of Patients
Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye Month 12- Other	0.5 Percentage of Patients	11.2 Percentage of Patients	3.6 Percentage of Patients

SECONDARY outcome

Timeframe: Day 1 and prior to month 3

Population: The Safety Set consisted of all patients who received at least one application of study treatment (ranibizumab \[sham\] and/or vPDT \[sham\]) and had at least one post-baseline safety assessment

In order to describe exposure to the study drug the number of ejections was evaluated

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=106 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=118 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT n=53 Participants Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Number of Ranibizumab Injections Received Prior to Month 3	2.5 injections Standard Deviation 0.57	1.8 injections Standard Deviation 0.82	0.0 injections Standard Deviation 0.00

SECONDARY outcome

Timeframe: Day 1 prior to month 6 and prior to month 12

Number of ranibizumab injections received by patients randomized to the ranibizumab groups, by period

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=106 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=118 Participants Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Number of Ranibizumab Injections Received by Patients Randomized to the Ranibizumab Groups, by Period Day 1 prior to Month 6	3.5 injections Standard Deviation 1.46	2.5 injections Standard Deviation 1.56	—
Number of Ranibizumab Injections Received by Patients Randomized to the Ranibizumab Groups, by Period Day 1 prior to month 12	4.6 injections Standard Deviation 2.59	3.5 injections Standard Deviation 2.92	—

SECONDARY outcome

Timeframe: Month 3 up to month 12

Number of ranibizumab injections received by patients randomized to the vPDT with ranibizumab groups, by period.

Outcome measures

Outcome measures
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=53 Participants Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Verteporfin PDT Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed.
Number of Ranibizumab Injections Received by Patients Randomized to vPDT With Ranibizumab From Month 3 by Period Day 1 up to month 6 (n=34)	1.9 injections Standard Deviation 0.86	—	—
Number of Ranibizumab Injections Received by Patients Randomized to vPDT With Ranibizumab From Month 3 by Period Day 1 up to month 12 (n=38)	3.2 injections Standard Deviation 2.54	—	—

Adverse Events

0.5 mg Ranibizumab Driven by Stabilization Criteria

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

0.5mg Ranibizumab Driven by Disease Activity

Serious events: 6 serious events

Other events: 47 other events

Deaths: 0 deaths

Visudyne PDT: Grp III With 0.5mg Ranibizumab From Month 3

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Visudyne PDT: Grp III Without 0.5mg Ranibizumab From Month 3

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	0.5 mg Ranibizumab Driven by Stabilization Criteria n=106 participants at risk Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity (VA).	0.5mg Ranibizumab Driven by Disease Activity n=118 participants at risk Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria	Visudyne PDT: Grp III With 0.5mg Ranibizumab From Month 3 n=38 participants at risk After month 3 participants received active ranibizumab, active vPDT or a combination of the two if needed.	Visudyne PDT: Grp III Without 0.5mg Ranibizumab From Month 3 n=15 participants at risk After month 3 participants did not receive active ranibizumab
Cardiac disorders Atrial tachycardia	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Cardiac disorders Myocarditis	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Eye disorders Corneal erosion (Study eye)	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Eye disorders Retinoschisis (Study eye)	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Gastrointestinal disorders Gastritis erosive	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Hepatobiliary disorders Hepatic function abnormal	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Injury, poisoning and procedural complications Joint dislocation	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Psychiatric disorders Depression	0.94% 1/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.
Renal and urinary disorders Renal failure chronic	0.00% 0/106 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.85% 1/118 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/38 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.	0.00% 0/15 Two participants who were randomized to Visudyne PDT received 0.5mg Ranibizumab and were followed up in the group "Driven by Disease Activity" therefore, the total of participants at risk in the safety section is discrepant by a number of 2 in each of these groups.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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 pooled data (i.e.,data from all sites) in clinical trial.
Publication restrictions are in place

Restriction type: OTHER