A Study Evaluating Dosing Regimens for Treatment With Int... | NCT01277302

ID	Type	Description	Link
ML01296	Other Identifier	Hoffmann-La Roche

Label	Type	Description	Intervention Names
Ranibizumab 0.5 mg monthly - randomized subjects	Experimental	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.	Drug: Ranibizumab
Ranibizumab 0.5 mg PRN - randomized subjects	Experimental	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm. No injection was given at the randomization visit. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.	Drug: Ranibizumab
Ranibizumab 0.5 mg monthly - non-randomized subjects	Experimental	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections and then never met the study-specific VA-OCT stability criteria from month 7 to month 14. Subjects were to receive 15 ranibizumab 0.5 mg injections.	Drug: Ranibizumab

Name	Type	Description	Arm Group Labels	Other Names
Ranibizumab	Drug	Liquid ranibizumab (10 mg/ml) was supplied in a sterile solution in single-use vials.	Ranibizumab 0.5 mg PRN - randomized subjects Ranibizumab 0.5 mg monthly - non-randomized subjects

Measure	Description	Time Frame
Trend of Change From Baseline in the Best Corrected Visual Acuity (BCVA) Scores From Month 7 to Month 15	BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement. The reported data are the observed changes from Baseline in BCVA at Months 7 and 15. For the statistical analysis, the interaction term of treatment by time in a longitudinal model was used to assess whether there was a difference in the trend of change from Baseline in the visual acuity scores from Month 7 to Month 15 between the 2 randomized treatment groups, Monthly and PRN.	Baseline to Month 15

Measure	Description	Time Frame
Visual Acuity Change From Previous Month During the Alternate Dose Regimen Period in Subjects Who Met the VA-OCT Stability Criteria at the Previous Month	BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement. This outcome measure is not relevant for subjects in the non-randomized group because they never met the VA-OCT stability criteria.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study.

Ocular Inclusion Criteria (Study Eye)

Foveal center-involved macular edema secondary to branch retinal vein occlusion (BRVO) (including hemi-retinal retinal vein occlusion [HRVO]) or central retinal vein occlusion (CRVO).
Best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/40 to 20/320 (Snellen equivalent) in the study eye.
Mean central subfield thickness > 300 µm on 2 spectral-domain optical coherence tomography measurements (screening and Day 0 [first day of treatment]).

Exclusion Criteria:

History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
History of any systemic anti-vascular endothelial growth factor (VEGF) or pro-VEGF treatment within 6 months prior to Day 0.
History of allergy to fluorescein.
History of allergy to ranibizumab injection or related molecule.
Relevant systemic disease that may be associated with increased systemic VEGF levels. History of successfully treated malignancies is not an exclusion criterion.
Uncontrolled blood pressure.
Pregnancy or lactation.
Daily use of oral corticosteroids to treat a chronic condition.
Required treatment with injectable corticosteroids to treat a musculoskeletal condition.
Participation in an investigational trial within 30 days prior to Day 0 that involved treatment with any drug or device that has not received regulatory approval at the time of study entry.

Ocular Exclusion Criteria (Study Eye)

Prior episode of retinal vein occlusion (RVO).
Brisk afferent pupillary defect.
History of any previous intravitreal anti-VEGF therapy for RVO in the study eye.
History of previous therapeutic treatment for RVO, other than anti-VEGF therapy, within 4 months prior to the screening visit, including any intraocular corticosteroids.
History of previous surgical treatment for RVO, including radial optic neurotomy or sheathotomy.
History or presence of age-related macular degeneration (AMD) (dry form graded as Age-Related Eye Disease Study [AREDS] Stage 2 or higher or wet form).
History of laser photocoagulation for macular edema within 4 months prior to Day 0.
History of panretinal scatter photocoagulation or sector laser photocoagulation within 4 months prior to Day 0 or anticipated within the next 4 months following Day 0.
History of pars plana vitrectomy.
History of intraocular surgery within 2 months prior to Day 0 or anticipated within the next 7 months following Day 0.
History of yttrium-aluminum-garnet (YAG) capsulotomy performed within 2 months prior to Day 0.
Previous filtration surgery in the study eye.
History of herpetic ocular infection.
History of ocular toxoplasmosis.
History of rhegmatogenous retinal detachment.
History of idiopathic central serous chorioretinopathy.
Evidence upon examination of vitreoretinal interface disease either on clinical examination or spectral-domain optical coherence tomography (SD-OCT), thought to be contributing to macular edema.
Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the study.
Visually significant hemorrhage obscuring the fovea and felt to be a major contributor to reduced visual acuity. The subject should be followed and when the hemorrhage in the fovea clears to the point that it is no longer a major contributor to reduced visual acuity, the subject may be screened for the study.
Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more.
Intra-ocular pressure (IOP) ≥ 30 mmHg. If a subject's IOP is ≥ 30 mmHg, that subject will be referred for glaucoma treatment and may be re-screened after 1 month.
Evidence upon examination of pseudoexfoliation.
Aphakia.
Evidence upon examination of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
Evidence upon examination of any diabetic retinopathy, defined as eyes of diabetic patients with more than one microaneurysm outside the area of the vein occlusion (inclusive of both eyes).
Other relevant ocular disease that may be associated with increased intraocular VEGF levels.
Improvement of ≥ 10 letters on best-corrected visual acuity ETDRS score between screening and Day 0.

Name	Affiliation	Role
Gary Sternberg, M.D.	Genentech, Inc.	Study Director

PubMed Identifier	Type	Citation	Retractions
36646240	Derived	Yiu G, Huang D, Wang Y, Wang Z, Yang M, Haskova Z. Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion. Am J Ophthalmol. 2023 May;249:74-81. doi: 10.1016/j.ajo.2023.01.004. Epub 2023 Jan 14.
30621653	Derived	Lloyd Clark W, Liu M, Kitchens J, Wang PW, Haskova Z. Baseline characteristics associated with early visual acuity gains after ranibizumab treatment for retinal vein occlusion. BMC Ophthalmol. 2019 Jan 8;19(1):11. doi: 10.1186/s12886-018-1012-y.

ID	Title	Description
FG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Trend of Change From Baseline in the Best Corrected Visual Acuity (BCVA) Scores From Month 7 to Month 15

BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement. The reported data are the observed changes from Baseline in BCVA at Months 7 and 15. For the statistical analysis, the interaction term of treatment by time in a longitudinal model was used to assess whether there was a difference in the trend of change from Baseline in the visual acuity scores from Month 7 to Month 15 between the 2 randomized treatment groups, Monthly and PRN.

Intent-to-treat population, randomized: All enrolled participants who received at least 1 ranibizumab injection in the study and were randomized into the Monthly or PRN treatment groups. The analysis was based on observed data without imputation for missing values.

Posted

Mean

Standard Deviation

Letters

Baseline to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Units	Counts
Participants	OG00085 OG00186

Title

Denominators

Categories

Month 7 (n=85, 86)

Title	Measurements
	OG00017.5± 12.6 OG00119.7± 12.6

Month 15 (n=80, 82)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis was that there was no difference in the trend of change from Baseline in the visual acuity scores from Month 7 to Month 15 between the 2 treatment groups as assessed by the interaction term of treatment by time in a longitudinal model.	Longitudinal mixed model	The analysis was stratified by disease (BRVO or CRVO), randomization month, and randomization BCVA score category (≤35, >35 to ≤50, or >50 letters).	0.5091	This is the p-value of the treatment by time interaction in the longitudinal model. Analysis was not adjusted for multiple comparisons as there was only 1 comparison. p < 0.05 (2-sided) was required for significance.	Estimated interaction effect	0.071	Standard Error of the Mean	0.107

Secondary

Visual Acuity Change From Previous Month During the Alternate Dose Regimen Period in Subjects Who Met the VA-OCT Stability Criteria at the Previous Month

Intent-to-treat population, randomized: All enrolled participants who received at least 1 ranibizumab injection in the study and were randomized into the monthly or PRN treatment groups. The analysis was based on observed data without imputation for missing values.

Posted

Mean

Standard Deviation

Letters

Month 7 through Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects

Secondary

Percentage of Participants Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 7 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Percentage of Participants With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better

VA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the EDTRS chart.

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 7 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Mean

Standard Deviation

Letters

Month 1 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Percentage of Participants Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 7 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Percentage of Participants With a Central Foveal Thickness of ≤ 300 µm

Central foveal thickness was assessed monthly in the study eye using spectral-domain optical coherence tomography. Central foveal thickness was computed using the automated Cirrus Review software (DOCTR CZM Cirrus OCT Grader Reading Manual, Version 1.02). All participants in the Monthly and PRN groups had a baseline central foveal thickness > 300 µm at baseline.

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 7 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Mean Change From Baseline in Central Foveal Thickness

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Mean

Standard Deviation

µm

Month 1 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Secondary

Percentage of Participants With Intraretinal Edema

The presence of intraretinal edema was defined as the presence of subretinal fluid, cystoid spaces, or central retinal thickness ≥ 300 µm as evaluated in spectral-domain optical coherence tomography images by the Digital Angiography Reading Center, the central reading center. At baseline, all participants in the Monthly and PRN groups had presence of edema.

Intent-to-treat population: All enrolled participants who received at least 1 ranibizumab injection in the study. The analysis was based on observed data without imputation for missing values.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 7 to Month 15

ID	Title	Description
OG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
OG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Angina unstable	Cardiac disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Coronary artery disease	Cardiac disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Sick sinus syndrome	Cardiac disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Intestinal infarction	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Chest pain	General disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Death	General disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Non-cardia chest pain	General disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Pain	General disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Cellulitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Diverticulitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Neck injury	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Benign lymph node neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Meningioma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Spinal cord neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Dementia	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Syncope	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Depression	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0011 affected86 at risk EG0020 affected31 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0010 affected86 at risk EG0020 affected31 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Macular hole	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Macular oedema	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Visual acuity reduced	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0001 affected85 at risk EG0013 affected86 at risk EG0020 affected31 at risk
Iridocyclitis	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk
Visual acuity reduced	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0000 affected85 at risk EG0010 affected86 at risk EG0021 affected31 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment		EG0001 affected85 at risk EG0012 affected86 at risk EG0022 affected31 at risk
Bronchitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0004 affected85 at risk EG0013 affected86 at risk EG0022 affected31 at risk
Nasopharyngitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG00010 affected85 at risk EG0017 affected86 at risk EG0021 affected31 at risk
Sinusitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0003 affected85 at risk EG0016 affected86 at risk EG0022 affected31 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0003 affected85 at risk EG0013 affected86 at risk EG0023 affected31 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment		EG0002 affected85 at risk EG0016 affected86 at risk EG0020 affected31 at risk
Blood pressure increased	Investigations	MedDRA (15.1)	Systematic Assessment		EG0002 affected85 at risk EG0011 affected86 at risk EG0022 affected31 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0002 affected85 at risk EG0015 affected86 at risk EG0020 affected31 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment		EG0007 affected85 at risk EG0015 affected86 at risk EG0020 affected31 at risk
Diabetic neuropathy	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0022 affected31 at risk
Headache	Nervous system disorders	MedDRA (15.1)	Systematic Assessment		EG0002 affected85 at risk EG0011 affected86 at risk EG0022 affected31 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment		EG0000 affected85 at risk EG0010 affected86 at risk EG0022 affected31 at risk
Hypertension	Vascular disorders	MedDRA (15.1)	Systematic Assessment		EG00013 affected85 at risk EG0018 affected86 at risk EG0022 affected31 at risk
Cataract	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0009 affected85 at risk EG0016 affected86 at risk EG0020 affected31 at risk
Cataract cortical	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0004 affected85 at risk EG0015 affected86 at risk EG0021 affected31 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG00028 affected85 at risk EG00123 affected86 at risk EG0029 affected31 at risk
Dry eye	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0004 affected85 at risk EG0013 affected86 at risk EG0022 affected31 at risk
Eye irritation	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0006 affected85 at risk EG0015 affected86 at risk EG0021 affected31 at risk
Eye pain	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0008 affected85 at risk EG00114 affected86 at risk EG0024 affected31 at risk
Eye pruritus	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0001 affected85 at risk EG0014 affected86 at risk EG0022 affected31 at risk
Macular fibrosis	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0009 affected85 at risk EG0015 affected86 at risk EG0022 affected31 at risk
Macular hole	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0001 affected85 at risk EG0010 affected86 at risk EG0022 affected31 at risk
Macular oedema	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0002 affected85 at risk EG0016 affected86 at risk EG0021 affected31 at risk
Retinal aneurysm	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0001 affected85 at risk EG0015 affected86 at risk EG0020 affected31 at risk
Retinal depigmentation	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0002 affected85 at risk EG0010 affected86 at risk EG0022 affected31 at risk
Retinal disorder	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0007 affected85 at risk EG0011 affected86 at risk EG0021 affected31 at risk
Retinal exudates	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG00013 affected85 at risk EG00112 affected86 at risk EG0023 affected31 at risk
Retinal haemorrhage	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0008 affected85 at risk EG0018 affected86 at risk EG0020 affected31 at risk
Retinal vascular disorder	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0003 affected85 at risk EG0015 affected86 at risk EG0020 affected31 at risk
Vitreous adhesions	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0000 affected85 at risk EG0010 affected86 at risk EG0023 affected31 at risk
Vitreous detachment	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG00011 affected85 at risk EG0016 affected86 at risk EG0023 affected31 at risk
Vitreous floaters	Eye disorders	MedDRA (15.1)	Systematic Assessment	Study eye	EG0004 affected85 at risk EG0016 affected86 at risk EG0021 affected31 at risk
Intraocular pressure increased	Investigations	MedDRA (15.1)	Systematic Assessment	Study eye	EG0003 affected85 at risk EG0018 affected86 at risk EG0021 affected31 at risk
Cataract	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0008 affected85 at risk EG0015 affected86 at risk EG0020 affected31 at risk
Dry eye	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0003 affected85 at risk EG0012 affected86 at risk EG0022 affected31 at risk
Retinal haemorrhage	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0004 affected85 at risk EG0016 affected86 at risk EG0020 affected31 at risk
Vitreous detachment	Eye disorders	MedDRA (15.1)	Systematic Assessment	Fellow eye	EG0007 affected85 at risk EG0012 affected86 at risk EG0021 affected31 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Phoenix	Arizona	85020	United States

ID	Term
D008268	Macular Degeneration
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
BG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.
BG002	Ranibizumab 0.5 mg Monthly - Non-randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections and then never met the study-specific VA-OCT stability criteria from month 7 to month 14. Subjects were to receive 15 ranibizumab 0.5 mg injections.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ranibizumab 0.5 mg Monthly - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.	12	85	70	85
EG001	Ranibizumab 0.5 mg PRN - Randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm and no injection was given. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.	14	86	61	86
EG002	Ranibizumab 0.5 mg Monthly - Non-randomized Subjects	Subjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections and then never met the study-specific VA-OCT stability criteria from month 7 to month 14. Subjects were to receive 15 ranibizumab 0.5 mg injections.	11	31	18	31