SUSTAIN - Study of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00331864
• Collaborator: (none)
• Enrollment: 531
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 22.1

Study Details

Study Description

Brief Summary

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A. This study will assess the safety and efficacy of ranibizumab administered on an as-needed dosing regimen in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration; Choroidal Neovascularization	Drug: Ranibizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 531 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIIb, Open-label, Multi-center 12 Month Study to Evaluate the Safety, Tolerability and Efficacy of Ranibizumab (0.3 mg and/or 0.5 mg) in Patients With Subfoveal Choroidal Neovasculariza-tion Secondary to Age-related Macular Degeneration
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Apr 1, 2008
• Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ranibizumab Ranibizumab-naïve (Non-ANCHOR) patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on re-treatment criteria described in the protocol. For patients who had participated in the ANCHOR study, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met re-treatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.

Drug: Ranibizumab; Other Names: rhuFab V2

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Ocular Adverse Events (AEs) in the Study Eye [Baseline through end of study (12 month treatment period)]

   Percentage of patients with ocular adverse events in the study eye over the one year (12 month) treatment period.

2. Percentage of Patients With Targeted Grade 3 Adverse Events (AEs) in the Study Eye [Baseline through end of study (12 month treatment period)]

   Grade 3 targeted AEs included: 4+ ocular inflammation or 2-3+ ocular inflammation failing to decrease to ≤ 1+ within 30 days ≥ 30 letter decrease in BCVA that developed within 14 days of ranibizumab injection sustained (>15 minutes) loss of light perception due to elevated intraocular pressure (IOP) or a >20 mm Hg change in IOP persisting longer than 14 days new retinal tear or detachment involving the macula new vitreous hemorrhage >2+ severity not resolving within 14 days new or increase of previous retinal hemorrhage >1 disc area in size and involving the fovea

Secondary Outcome Measures

1. Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 3 [Baseline and Month 3]

   BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.

2. Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 12 [Baseline and Month 12]

   BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.

3. Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 3 [Baseline and Month 3]

   Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).

4. Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 12 [Baseline and Month 12]

   Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).

5. Time to the First Retreatment After Month 2 [Month 2 to Month 11]

   Time to first re-treatment is calculated as time difference in months starting from Month 2 until the month of first re-treatment. Criteria for re-treatment: a >5 letter decrease in BCVA (determined using EDRS charts) based upon the highest visual acuity score from any prior scheduled study visit (Months 0, 1, 2 or 3) a >100 µm increase in central retinal thickness (determined using OCT) from the thinnest measurement from any prior scheduled study visit (Months 0, 1, 2 or 3)

6. Total Number of Treatments [Baseline (Month 0) to Month 11]

   Total number of treatments administered during the entire treatment period (Month 0 to 11).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Patients who participated in this study included those who had completed participation in the study CRFB002A2301 (ANCHOR; NCT00061594), newly diagnosed patients, as well as previously diagnosed patients who had had recent disease progression.

Inclusion Criteria:

• Male or female patients > 50 years of age

• Diagnosis of active primary or recurrent CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component

• The total area of CNV (including both classic and occult components) encompassed within the lesion must be >= 50% of the total lesion area

• The total lesion area must be <= 12 disc areas

• Patients who have a BCVA (best corrected visual acuity) score between 73 and 24 letters, inclusive, in the study eye using ETDRS-like (Early Treatment of Diabetic Retinopathy Study) grading charts (approximately 20/40 to 20/320)

Exclusion Criteria:

• Patients who have a BCVA of < 34 letters in both eyes (legally blind is defined as bilateral vision below 20/200 or less than 34 letters)

• Laser photocoagulation, treatment with intravitreal steroids, verteporfin photo dynamic therapy or pegaptanib sodium in the study eye within 30 days preceding Day 1

• Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis - 64 sites in 11 countries	Basel		Switzerland

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis Customer Information, Novartis - Including Sites in Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00331864
• Other Study ID Numbers: CRFB002A2303
• First Posted: May 31, 2006
• Last Update Posted: Feb 18, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: AMD, ranibizumab
• Additional relevant MeSH terms: Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Ranibizumab

Study Results

Participant Flow

Recruitment Details	The study population consisted of two groups, one group being naïve to ranibizumab ("Non-ANCHOR" patients) and the other group were those patients who previously were treated with ranibizumab in the ANCHOR study (NCT00061594; "ANCHOR" patients).

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Period Title: Overall Study
STARTED	513	18
COMPLETED	455	14
NOT COMPLETED	58	4

Baseline Characteristics

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR	Total
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Total of all reporting groups
Overall Participants	513	18	531
Age, Customized (participants) [Number]
< 50 years	1 0.2%	0 0%	1 0.2%
50 to < 65 years	49 9.6%	0 0%	49 9.2%
65 to < 75 years	173 33.7%	5 27.8%	178 33.5%
75 to < 85 years	230 44.8%	12 66.7%	242 45.6%
≥ 85 years	60 11.7%	1 5.6%	61 11.5%
Sex: Female, Male (Count of Participants)
Female	294 57.3%	9 50%	303 57.1%
Male	219 42.7%	9 50%	228 42.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Ocular Adverse Events (AEs) in the Study Eye
Description	Percentage of patients with ocular adverse events in the study eye over the one year (12 month) treatment period.
Time Frame	Baseline through end of study (12 month treatment period)

Outcome Measure Data

Analysis Population Description

For Non-ANCHOR treatment group, the analysis population was the Safety population: All patients who had received at least one application of study drug and had at least one post-baseline safety assessment. For the ANCHOR treatment group, the analysis population was all enrolled patients.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	513	18
Number [Percentage of Participants]	48.5 9.5%	38.9 216.1%

2. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 3
Description	BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.
Time Frame	Baseline and Month 3

Outcome Measure Data

Analysis Population Description

Non-ANCHOR patients: Analysis of Intent-to-Treat (ITT) population (all patients who received study drug at least once and had at least one post-baseline efficacy assessment) using last observation carried forward (LOCF). ANCHOR patients: Analysis of All Enrolled population (all enrolled patients) using LOCF.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	509	15
Baseline	56.2 (12.11)	47.2 (22.10)
Change to Month 3	5.8 (11.12)	1.9 (9.26)

3. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 12
Description	BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Non-ANCHOR patients: Analysis of Intent-to-Treat (ITT) population (all patients who received study drug at least once and had at least one post-baseline efficacy assessment) using last observation carried forward (LOCF). ANCHOR patients: Analysis of All Enrolled population (all enrolled patients) using LOCF.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	509	17
Baseline	56.2 (12.11)	47.2 (22.10)
Change to Month 12	3.6 (13.89)	1.6 (8.66)

4. Secondary Outcome

Title	Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 3
Description	Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).
Time Frame	Baseline and Month 3

Outcome Measure Data

Analysis Population Description

Non-ANCHOR patients: Analysis of Intent-to-Treat (ITT) population (all patients who received study drug at least once and had at least one post-baseline efficacy assessment) using last observation carried forward (LOCF). ANCHOR patients: Analysis of All Enrolled population (all enrolled patients) using LOCF.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	507	15
Baseline	339.6 (109.38)	214.1 (64.92)
Change to Month 3	-101.1 (115.69)	36.3 (72.96)

5. Secondary Outcome

Title	Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 12
Description	Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Non-ANCHOR patients: Analysis of Intent-to-Treat (ITT) population (all patients who received study drug at least once and had at least one post-baseline efficacy assessment) using last observation carried forward (LOCF). ANCHOR patients: Analysis of All Enrolled population (all enrolled patients) using LOCF.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	507	17
Baseline	339.6 (109.38)	214.1 (64.92)
Change to Month 12	-91.5 (115.47)	39.3 (84.61)

6. Secondary Outcome

Title	Time to the First Retreatment After Month 2
Description	Time to first re-treatment is calculated as time difference in months starting from Month 2 until the month of first re-treatment. Criteria for re-treatment: a >5 letter decrease in BCVA (determined using EDRS charts) based upon the highest visual acuity score from any prior scheduled study visit (Months 0, 1, 2 or 3) a >100 µm increase in central retinal thickness (determined using OCT) from the thinnest measurement from any prior scheduled study visit (Months 0, 1, 2 or 3)
Time Frame	Month 2 to Month 11

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population patients: All patients who received study drug at least once and had at least one post-baseline efficacy assessment. The ANCHOR patients were not included in this analysis.

Arm/Group Title	Ranibizumab Non-ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	500
Median (Inter-Quartile Range) [Months]	2

7. Secondary Outcome

Title	Total Number of Treatments
Description	Total number of treatments administered during the entire treatment period (Month 0 to 11).
Time Frame	Baseline (Month 0) to Month 11

Outcome Measure Data

Analysis Population Description

For Non-ANCHOR treatment group, the analysis population was the Safety population: All patients who had received at least one application of study drug and had at least one post-baseline safety assessment. For the ANCHOR treatment group, the analysis population was all enrolled patients.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	513	18
Mean (Standard Deviation) [Treatments]	5.6 (2.37)	1.1 (2.29)

8. Primary Outcome

Title	Percentage of Patients With Targeted Grade 3 Adverse Events (AEs) in the Study Eye
Description	Grade 3 targeted AEs included: 4+ ocular inflammation or 2-3+ ocular inflammation failing to decrease to ≤ 1+ within 30 days ≥ 30 letter decrease in BCVA that developed within 14 days of ranibizumab injection sustained (>15 minutes) loss of light perception due to elevated intraocular pressure (IOP) or a >20 mm Hg change in IOP persisting longer than 14 days new retinal tear or detachment involving the macula new vitreous hemorrhage >2+ severity not resolving within 14 days new or increase of previous retinal hemorrhage >1 disc area in size and involving the fovea
Time Frame	Baseline through end of study (12 month treatment period)

Outcome Measure Data

Analysis Population Description

For Non-ANCHOR treatment group, the analysis population was the Safety population: All patients who had received at least one application of study drug and had at least one post-baseline safety assessment. For the ANCHOR treatment group, the analysis population was all enrolled patients.

Arm/Group Title	Ranibizumab Non-ANCHOR	Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.	Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
Measure Participants	513	18
Number [Percentage of Participants]	2.9 0.6%	0.0 0%

Adverse Events

Arm/Group Title	Ranibizumab Non-ANCHOR		Ranibizumab ANCHOR
Arm/Group Description	Patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.		Patients received up to 12 intravitreal injections (Month 0 through Month 11). From Month 0 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met retreatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.
All Cause Mortality
	Ranibizumab Non-ANCHOR		Ranibizumab ANCHOR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab Non-ANCHOR		Ranibizumab ANCHOR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/513 (15.6%)		4/18 (22.2%)
Blood and lymphatic system disorders
Anaemia	1/513 (0.2%)		1/18 (5.6%)
Cardiac disorders
Acute coronary syndrome	1/513 (0.2%)		0/18 (0%)
Acute myocardial infarction	1/513 (0.2%)		1/18 (5.6%)
Angina pectoris	3/513 (0.6%)		0/18 (0%)
Arrhythmia	3/513 (0.6%)		0/18 (0%)
Atrial fibrillation	2/513 (0.4%)		1/18 (5.6%)
Cardiac failure	6/513 (1.2%)		0/18 (0%)
Cardiogenic shock	1/513 (0.2%)		0/18 (0%)
Coronary artery disease	1/513 (0.2%)		0/18 (0%)
Intracardiac thrombus	1/513 (0.2%)		0/18 (0%)
Myocardial infarction	5/513 (1%)		0/18 (0%)
Myocardial ischaemia	1/513 (0.2%)		0/18 (0%)
Silent myocardial infarction	1/513 (0.2%)		0/18 (0%)
Ear and labyrinth disorders
Vertigo	1/513 (0.2%)		0/18 (0%)
Vestibular disorder	1/513 (0.2%)		0/18 (0%)
Eye disorders
Cataract (Fellow eye)	3/513 (0.6%)		0/18 (0%)
Cataract (Study eye)	1/513 (0.2%)		0/18 (0%)
Choroidal neovascularisation (Fellow eye)	1/513 (0.2%)		0/18 (0%)
Retinal haemorrhage (Study eye)	2/513 (0.4%)		0/18 (0%)
Retinal pigment epithelial tear (Study eye)	1/513 (0.2%)		0/18 (0%)
Visual acuity reduced (Study eye)	1/513 (0.2%)		0/18 (0%)
Vitreous haemorrhage (Study eye)	1/513 (0.2%)		0/18 (0%)
Gastrointestinal disorders
Abdominal pain	1/513 (0.2%)		0/18 (0%)
Duodenal ulcer	1/513 (0.2%)		0/18 (0%)
Gastric haemorrhage	1/513 (0.2%)		0/18 (0%)
Gastric ulcer haemorrhage	1/513 (0.2%)		0/18 (0%)
Gastritis erosive	1/513 (0.2%)		0/18 (0%)
Haematemesis	1/513 (0.2%)		0/18 (0%)
Hiatus hernia	1/513 (0.2%)		0/18 (0%)
Intestinal obstruction	2/513 (0.4%)		0/18 (0%)
Pancreatitis	1/513 (0.2%)		0/18 (0%)
General disorders
Asthenia	2/513 (0.4%)		0/18 (0%)
Chest pain	1/513 (0.2%)		0/18 (0%)
Death	1/513 (0.2%)		0/18 (0%)
Infections and infestations
Bronchitis	2/513 (0.4%)		0/18 (0%)
Bronchopneumonia	1/513 (0.2%)		0/18 (0%)
Clostridium difficile colitis	1/513 (0.2%)		0/18 (0%)
Gangrene	1/513 (0.2%)		0/18 (0%)
Infected skin ulcer	1/513 (0.2%)		0/18 (0%)
Pneumonia	2/513 (0.4%)		0/18 (0%)
Respiratory tract infection	1/513 (0.2%)		0/18 (0%)
Sepsis	2/513 (0.4%)		0/18 (0%)
Urinary tract infection	1/513 (0.2%)		0/18 (0%)
Injury, poisoning and procedural complications
Contusion	1/513 (0.2%)		0/18 (0%)
Fall	0/513 (0%)		1/18 (5.6%)
Femur fracture	1/513 (0.2%)		0/18 (0%)
Hip fracture	1/513 (0.2%)		0/18 (0%)
Humerus fracture	0/513 (0%)		1/18 (5.6%)
Joint injury	1/513 (0.2%)		0/18 (0%)
Limb injury	1/513 (0.2%)		0/18 (0%)
Lumbar vertebral fracture	1/513 (0.2%)		0/18 (0%)
Pelvic fracture	0/513 (0%)		1/18 (5.6%)
Rib fracture	1/513 (0.2%)		0/18 (0%)
Road traffic accident	1/513 (0.2%)		0/18 (0%)
Skeletal injury	1/513 (0.2%)		0/18 (0%)
Upper limb fracture	1/513 (0.2%)		0/18 (0%)
Wrist fracture	1/513 (0.2%)		0/18 (0%)
Investigations
Blood urine present	1/513 (0.2%)		0/18 (0%)
Cardioactive drug level increased	1/513 (0.2%)		0/18 (0%)
Metabolism and nutrition disorders
Dehydration	1/513 (0.2%)		0/18 (0%)
Diabetes mellitus inadequate control	1/513 (0.2%)		0/18 (0%)
Metabolic acidosis	1/513 (0.2%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Back pain	4/513 (0.8%)		0/18 (0%)
Mobility decreased	1/513 (0.2%)		0/18 (0%)
Musculoskeletal chest pain	1/513 (0.2%)		0/18 (0%)
Osteoporosis	1/513 (0.2%)		0/18 (0%)
Pain in extremity	1/513 (0.2%)		0/18 (0%)
Spinal column stenosis	1/513 (0.2%)		0/18 (0%)
Spinal osteoarthritis	1/513 (0.2%)		0/18 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/513 (0.2%)		0/18 (0%)
Bladder cancer	2/513 (0.4%)		0/18 (0%)
Breast cancer	3/513 (0.6%)		0/18 (0%)
Colon adenoma	1/513 (0.2%)		0/18 (0%)
Colon cancer	3/513 (0.6%)		0/18 (0%)
Extranodal marginal zone B-cell lymphoma (MALT type)	0/513 (0%)		1/18 (5.6%)
Gastrointestinal neoplasm	1/513 (0.2%)		0/18 (0%)
Laryngeal neoplasm	1/513 (0.2%)		0/18 (0%)
Lymphoma	1/513 (0.2%)		0/18 (0%)
Metastases to lung	1/513 (0.2%)		0/18 (0%)
Metastatic neoplasm	1/513 (0.2%)		0/18 (0%)
Myelodysplastic syndrome	2/513 (0.4%)		0/18 (0%)
Neuroma	1/513 (0.2%)		0/18 (0%)
Prostate cancer	2/513 (0.4%)		0/18 (0%)
Prostate cancer metastatic	1/513 (0.2%)		0/18 (0%)
Renal cell carcinoma	1/513 (0.2%)		0/18 (0%)
Renal neoplasm	1/513 (0.2%)		0/18 (0%)
Thyroid cancer	1/513 (0.2%)		0/18 (0%)
Nervous system disorders
Cerebral infarction	1/513 (0.2%)		0/18 (0%)
Cerebrovascular accident	1/513 (0.2%)		1/18 (5.6%)
Diabetic coma	1/513 (0.2%)		0/18 (0%)
Dizziness	1/513 (0.2%)		0/18 (0%)
Hypoaesthesia	0/513 (0%)		1/18 (5.6%)
Presyncope	1/513 (0.2%)		0/18 (0%)
Sciatica	1/513 (0.2%)		0/18 (0%)
Syncope	1/513 (0.2%)		0/18 (0%)
Transient ischaemic attack	2/513 (0.4%)		0/18 (0%)
Renal and urinary disorders
Renal failure	1/513 (0.2%)		0/18 (0%)
Renal failure acute	1/513 (0.2%)		0/18 (0%)
Renal failure chronic	1/513 (0.2%)		0/18 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/513 (0%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/513 (0.2%)		0/18 (0%)
Chronic obstructive pulmonary disease	1/513 (0.2%)		0/18 (0%)
Dyspnoea	2/513 (0.4%)		0/18 (0%)
Lung disorder	1/513 (0.2%)		0/18 (0%)
Pleural effusion	1/513 (0.2%)		0/18 (0%)
Pulmonary embolism	2/513 (0.4%)		0/18 (0%)
Pulmonary oedema	1/513 (0.2%)		0/18 (0%)
Respiratory failure	1/513 (0.2%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/513 (0.2%)		0/18 (0%)
Vascular disorders
Aortic aneurysm rupture	1/513 (0.2%)		0/18 (0%)
Arteriosclerosis	1/513 (0.2%)		0/18 (0%)
Circulatory collapse	2/513 (0.4%)		0/18 (0%)
Deep vein thrombosis	1/513 (0.2%)		0/18 (0%)
Hypertension	2/513 (0.4%)		0/18 (0%)
Hypotension	1/513 (0.2%)		0/18 (0%)
Peripheral embolism	1/513 (0.2%)		0/18 (0%)
Poor peripheral circulation	1/513 (0.2%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Ranibizumab Non-ANCHOR		Ranibizumab ANCHOR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	199/513 (38.8%)		8/18 (44.4%)
Eye disorders
Choroidal neovascularisation (Fellow eye)	16/513 (3.1%)		2/18 (11.1%)
Choroidal neovascularisation (Study eye)	8/513 (1.6%)		2/18 (11.1%)
Conjunctival haemorrhage (Study eye)	28/513 (5.5%)		0/18 (0%)
Retinal haemorrhage (Fellow eye)	12/513 (2.3%)		2/18 (11.1%)
Retinal haemorrhage (Study eye)	35/513 (6.8%)		5/18 (27.8%)
Retinal oedema (Study eye)	8/513 (1.6%)		2/18 (11.1%)
Visual acuity reduced (Fellow eye)	23/513 (4.5%)		1/18 (5.6%)
Visual acuity reduced (Study eye)	94/513 (18.3%)		1/18 (5.6%)
Investigations
Intraocular pressure increased (Study eye)	36/513 (7%)		0/18 (0%)
Nervous system disorders
Headache	13/513 (2.5%)		1/18 (5.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.