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A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-related Macular Degeneration (HARBOR)

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00891735
Collaborator
(none)
1,097
Enrollment
99
Locations
4
Arms
37
Duration (Months)
11.1
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase III, multicenter, randomized, double-masked, dose-comparison study of the efficacy and safety of ranibizumab injection administered intravitreally to patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Results are presented for the first 12 months of the study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1097 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis (PRN) in Patients With Subfoveal Neovascular Age-related Macular Degeneration
Study Start Date :
Jul 1, 2009
Actual Primary Completion Date :
Aug 1, 2011
Actual Study Completion Date :
Aug 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ranibizumab 0.5 mg monthly

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 24 months.

Drug: Ranibizumab
Sterile solution for intravitreal injection.
Other Names:
  • Lucentis

    		•
    Experimental: Ranibizumab 2.0 mg monthly

    Patients received ranibizumab 2.0 mg monthly administered intravitreally for 24 months.

    Drug: Ranibizumab
    Sterile solution for intravitreal injection.
    Other Names:
  • Lucentis

    		•
    Experimental: Ranibizumab 0.5 mg as-needed (pro re nata [PRN])

    Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.

    Drug: Ranibizumab
    Sterile solution for intravitreal injection.
    Other Names:
  • Lucentis

    		•
    Experimental: Ranibizumab 2.0 mg as-needed (pro re nata [PRN])

    Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.

    Drug: Ranibizumab
    Sterile solution for intravitreal injection.
    Other Names:
  • Lucentis

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 [Baseline to Month 12]

      BCVA was measured 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. A decrease in the BCVA score indicates a worsening of vision. A positive change score indicates improvement.

    Secondary Outcome Measures

    1. Number of Ranibizumab Injections up to But Not Including Month 12 [Baseline to Month 12]

    2. Percentage of Patients Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Month 12 [Baseline to Month 12]

      BCVA was measured 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.

    3. Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Month 12 [Month 12]

      VA was measured 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 is 14 lines correctly read in the EDTRS chart.

    4. Percentage of Patients With no Evidence of Fluid From Choroidal Neovascularization (CNV) at Month 12 [Month 12]

      The presence of fluid from choroidal neovascularization (CNV) was assessed by spectral domain optical coherence tomography (SD-OCT). No evidence of fluid was defined as no subretinal fluid thickness, no cystoid spaces, no intraretinal fluid, no pigment epithelial defect thickness, and average central subfield thickness < 270 µm.

    5. Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 [Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12]

      Central foveal thickness was assessed by spectral domain optical coherence tomography (SD-OCT).

    6. Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 [Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12]

      Macular volume was assessed by spectral domain optical coherence tomography (SD-OCT).

    7. Change From Baseline in the Total Area of Choroidal Neovascularization (CNV) and Choroidal Neovascular Leakage at Month 12 [Baseline to Month 12]

      The total area of choroidal neovascularization (CNV) and choroidal neovascular leakage was assessed with fluorescein angiography (FA). Area was measured in disc area units; 1 disc area unit = 2.54 mm^2.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • For sexually active women of childbearing potential, agreement to the use of an appropriate form of contraception (or abstinence) for the duration of the study.

    Ocular Inclusion Criteria (Study Eye)

    • Best corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, of 20/40-20/320 (Snellen equivalent).

    • Choroidal neovascularization (CNV) lesions with classic CNV component, occult CNV, or with some classic CNV component were permissible.

    • Total area of lesion < 12 disc area or 30.48 mm^2.

    Exclusion Criteria:

    • History of vitrectomy surgery, submacular surgery, or other surgical intervention for age-related macular degeneration (AMD) in the study eye.

    • Prior treatment with Visudyne(R), external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye.

    • Previous intravitreal drug delivery (eg, intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation) in the study eye.

    • Previous treatment or participation in a clinical trial involving anti-angiogenic drugs (Avastin(R), anecortave acetate, protein kinase C inhibitors, etc), in the non-study eye within 3 months of Day 0 (first day of treatment). The patient may not have received Lucentis(R) or Macugen(R) in the non-study eye within 7 days of Day 0.

    • Treatment with Visudyne(R) in the non-study eye < 7 days preceding Day 0.

    • Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either > 50% of the total area of the lesion or > 1 disc area (2.54 mm^2) in size.

    • Subfoveal fibrosis or atrophy in the study eye.

    • CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.

    • Retinal pigment epithelial tear involving the macula in the study eye.

    • Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could either: Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition; or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity (BCVA) over the 24-month study period.

    • Uncontrolled blood pressure.

    • Atrial fibrillation not managed by patient's primary care physician or cardiologist within 3 months of screening visit.

    • History of stroke within the last 3 months of screening visit.

    • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications.

    • Current treatment for active systemic infection.

    • Active malignancy.

    • History of allergy to fluorescein, not amenable to treatment.

    • Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States 85020
    2 Tucson Arizona United States 85704
    3 Arcadia California United States 91007
    4 Beverly Hills California United States 90211
    5 Campbell California United States 95008
    6 Chico California United States 95973
    7 La Jolla California United States 92093-0946
    8 Los Angeles California United States 90033
    9 Los Angeles California United States 90095-7000
    10 Mountain View California United States 94040
    11 Oakland California United States 94609
    12 Palm Desert California United States 92211
    13 Poway California United States 92064
    14 Sacramento California United States 95817
    15 San Francisco California United States 94107
    16 San Francisco California United States 94115
    17 Santa Ana California United States 92705
    18 Santa Barbara California United States 93103
    19 Torrance California United States 90503
    20 Ventura California United States 93003
    21 Westlake Village California United States 91361
    22 Aurora Colorado United States 80045
    23 Colorado Springs Colorado United States 80909
    24 Golden Colorado United States 80401
    25 Danbury Connecticut United States 06810
    26 Hamden Connecticut United States 06518
    27 New Haven Connecticut United States 06510
    28 New London Connecticut United States 06320
    29 Altamonte Springs Florida United States 32701
    30 Boynton Beach Florida United States 33426
    31 Fort Lauderdale Florida United States 33334
    32 Fort Myers Florida United States 33912
    33 Palm Beach Gardens Florida United States 33410
    34 Pensacola Florida United States 32503
    35 Stuart Florida United States 34994
    36 Tampa Florida United States 33609
    37 Tampa Florida United States 33612
    38 Winter Haven Florida United States 33880
    39 Augusta Georgia United States 30909
    40 Aiea Hawaii United States 96701
    41 Chicago Illinois United States 60637
    42 Oak Park Illinois United States 60304
    43 Indianapolis Indiana United States 46290
    44 Shawnee Mission Kansas United States 66204
    45 Wichita Kansas United States 67214
    46 Lexington Kentucky United States 40509
    47 Paducah Kentucky United States 42001
    48 Portland Maine United States 04102
    49 Baltimore Maryland United States 21287
    50 Hagerstown Maryland United States 21740
    51 Boston Massachusetts United States 02111
    52 Boston Massachusetts United States 02114
    53 Worcester Massachusetts United States 01605
    54 Jackson Michigan United States 49201
    55 Edina Minnesota United States 55435
    56 Saint Louis Missouri United States 63144
    57 Lincoln Nebraska United States 68506
    58 Las Vegas Nevada United States 89144
    59 Lawrenceville New Jersey United States 08648
    60 New Brunswick New Jersey United States 08901
    61 Northfield New Jersey United States 08225
    62 Teaneck New Jersey United States 07666
    63 Vauxhall New Jersey United States 07088
    64 Great Neck New York United States 11021
    65 Lynbrook New York United States 11563
    66 New York New York United States 10021
    67 Rochester New York United States 14620
    68 Shirley New York United States 11967
    69 Asheville North Carolina United States 28803
    70 Charlotte North Carolina United States 28210
    71 Beachwood Ohio United States 44122
    72 Cincinnati Ohio United States 45242
    73 Columbus Ohio United States 43212
    74 Portland Oregon United States 97210
    75 Camp Hill Pennsylvania United States 17011
    76 Huntingdon Valley Pennsylvania United States 19006
    77 Johnstown Pennsylvania United States 15904
    78 Philadelphia Pennsylvania United States 19107
    79 Pittsburgh Pennsylvania United States 15212
    80 Pittsburgh Pennsylvania United States 15213
    81 West Mifflin Pennsylvania United States 15122
    82 Greenville South Carolina United States 29605
    83 Ladson South Carolina United States 29456
    84 West Columbia South Carolina United States 29169
    85 Rapid City South Dakota United States 57701
    86 Nashville Tennessee United States 37203
    87 Abilene Texas United States 79606
    88 Austin Texas United States 78705
    89 Desoto Texas United States 75115
    90 Houston Texas United States 77030
    91 McAllen Texas United States 78503
    92 San Antonio Texas United States 78240
    93 Temple Texas United States 76508
    94 The Woodlands Texas United States 77384
    95 Salt Lake City Utah United States 84107
    96 Richmond Virginia United States 23235
    97 Virginia Beach Virginia United States 23454
    98 Milwaukee Wisconsin United States 53226
    99 Casper Wyoming United States 82601

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT00891735
    Other Study ID Numbers:
    • FVF4579g
    • GX01511
    First Posted:
    May 1, 2009
    Last Update Posted:
    Jan 18, 2013
    Last Verified:
    Dec 1, 2012
    Keywords provided by Genentech, Inc.
    Lucentis
    AMD
    Age-related macular degeneration
    Subfoveal neovascular age-related macular degeneration
    Wet AMD
    Macular degeneration
    Ranibizumab
    Additional relevant MeSH terms:
    Macular Degeneration
    Wet Macular Degeneration
    Ranibizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Period Title: Overall Study
    STARTED 275 274 275 273
    COMPLETED 258 258 263 258
    NOT COMPLETED 17 16 12 15

    Baseline Characteristics

    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) Total
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally. Total of all reporting groups
    Overall Participants 275 274 275 273 1097
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    78.8
    (8.4)
    79.3
    (8.3)
    78.5
    (8.3)
    78.3
    (8.3)
    78.7
    (8.3)
    Sex: Female, Male (Count of Participants)
    Female
    162
    58.9%
    170
    62%
    163
    59.3%
    156
    57.1%
    651
    59.3%
    Male
    113
    41.1%
    104
    38%
    112
    40.7%
    117
    42.9%
    446
    40.7%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12
    Description BCVA was measured 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. A decrease in the BCVA score indicates a worsening of vision. A positive change score indicates improvement.
    Time Frame Baseline to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Mean (Standard Deviation) [Letters]
    10.1
    (13.3)
    9.2
    (14.6)
    8.2
    (13.3)
    8.6
    (13.8)
    2. Secondary Outcome
    Title Number of Ranibizumab Injections up to But Not Including Month 12
    Description
    Time Frame Baseline to Month 12

    Outcome Measure Data

    Analysis Population Description
    All treated patients. Observed data were used with no imputation.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 274 274 275 272
    Mean (Standard Deviation) [Injections]
    11.3
    (1.8)
    11.2
    (2.1)
    7.7
    (2.7)
    6.9
    (2.4)
    3. Secondary Outcome
    Title Percentage of Patients Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Month 12
    Description BCVA was measured 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.
    Time Frame Baseline to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Number (95% Confidence Interval) [Percentage of patients]
    34.5
    36.1
    30.2
    33.0
    4. Secondary Outcome
    Title Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Month 12
    Description VA was measured 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 is 14 lines correctly read in the EDTRS chart.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Number (95% Confidence Interval) [Percentage of patients]
    52.4
    50.0
    46.2
    43.6
    5. Secondary Outcome
    Title Percentage of Patients With no Evidence of Fluid From Choroidal Neovascularization (CNV) at Month 12
    Description The presence of fluid from choroidal neovascularization (CNV) was assessed by spectral domain optical coherence tomography (SD-OCT). No evidence of fluid was defined as no subretinal fluid thickness, no cystoid spaces, no intraretinal fluid, no pigment epithelial defect thickness, and average central subfield thickness < 270 µm.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Number (95% Confidence Interval) [Percentage of patients]
    5.1
    5.8
    2.9
    4.8
    6. Secondary Outcome
    Title Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12
    Description Central foveal thickness was assessed by spectral domain optical coherence tomography (SD-OCT).
    Time Frame Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Day 7
    -104.9
    (130.3)
    -84.9
    (111.3)
    -103.5
    (141.3)
    -100.6
    (123.4)
    Month 1
    -141.5
    (137.5)
    -128.6
    (133.3)
    -132.6
    (148.2)
    -146.0
    (144.3)
    Month 2
    -152.5
    (142.4)
    -140.3
    (131.1)
    -142.9
    (141.6)
    -156.9
    (145.0)
    Month 3
    -157.0
    (143.8)
    -147.9
    (134.3)
    -154.5
    (147.9)
    -164.9
    (144.5)
    Month 4
    -164.0
    (146.6)
    -151.8
    (143.3)
    -142.7
    (153.6)
    -159.7
    (148.8)
    Month 6
    -162.0
    (150.0)
    -149.2
    (144.0)
    -147.5
    (151.9)
    -159.1
    (149.6)
    Month 9
    -164.5
    (151.8)
    -153.1
    (144.8)
    -153.5
    (147.1)
    -157.8
    (155.6)
    Month 12
    -172.0
    (150.5)
    -163.3
    (142.6)
    -161.2
    (152.3)
    -172.4
    (148.6)
    7. Secondary Outcome
    Title Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12
    Description Macular volume was assessed by spectral domain optical coherence tomography (SD-OCT).
    Time Frame Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Day 7
    -0.79
    (0.80)
    -0.80
    (0.76)
    -0.72
    (0.87)
    -0.81
    (0.76)
    Month 1
    -1.26
    (1.06)
    -1.30
    (1.15)
    -1.16
    (1.03)
    -1.38
    (1.18)
    Month 2
    -1.34
    (1.17)
    -1.49
    (1.31)
    -1.30
    (1.13)
    -1.47
    (1.25)
    Month 3
    -1.42
    (1.25)
    -1.51
    (1.32)
    -1.43
    (1.33)
    -1.55
    (1.28)
    Month 4
    -1.42
    (1.22)
    -1.56
    (1.31)
    -1.31
    (1.24)
    -1.48
    (1.27)
    Month 6
    -1.47
    (1.25)
    -1.61
    (1.34)
    -1.35
    (1.33)
    -1.48
    (1.36)
    Month 9
    -1.55
    (1.41)
    -1.67
    (1.34)
    -1.35
    (1.31)
    -1.48
    (1.33)
    Month 12
    -1.54
    (1.31)
    -1.66
    (1.37)
    -1.41
    (1.36)
    -1.49
    (1.35)
    8. Secondary Outcome
    Title Change From Baseline in the Total Area of Choroidal Neovascularization (CNV) and Choroidal Neovascular Leakage at Month 12
    Description The total area of choroidal neovascularization (CNV) and choroidal neovascular leakage was assessed with fluorescein angiography (FA). Area was measured in disc area units; 1 disc area unit = 2.54 mm^2.
    Time Frame Baseline to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    Measure Participants 275 274 275 273
    Change in the total area of CNV
    -2.14
    (2.40)
    -2.42
    (2.38)
    -1.74
    (2.22)
    -1.98
    (2.39)
    Change in the total area of CNV leakage
    -2.35
    (2.39)
    -2.63
    (2.34)
    -2.01
    (2.28)
    -2.22
    (2.48)

    Adverse Events

    Time Frame Adverse events were recorded from Baseline (first treatment day) through Month 12.
    Adverse Event Reporting Description Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
    Arm/Group Title Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Arm/Group Description Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months. Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally. Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
    All Cause Mortality
    Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 66/274 (24.1%) 54/274 (19.7%) 57/275 (20.7%) 54/272 (19.9%)
    Blood and lymphatic system disorders
    Anaemia 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Hypocoagulable state 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Cardiac disorders
    Acute myocardial infarction 1/274 (0.4%) 1/274 (0.4%) 0/275 (0%) 1/272 (0.4%)
    Angina pectoris 1/274 (0.4%) 1/274 (0.4%) 1/275 (0.4%) 1/272 (0.4%)
    Angina unstable 2/274 (0.7%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Arrhythmia 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Arteriosclerosis coronary artery 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Atrial fibrillation 2/274 (0.7%) 1/274 (0.4%) 4/275 (1.5%) 4/272 (1.5%)
    Atrioventricular block complete 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Cardiac arrest 3/274 (1.1%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Cardiac failure congestive 6/274 (2.2%) 1/274 (0.4%) 2/275 (0.7%) 2/272 (0.7%)
    Coronary artery disease 0/274 (0%) 0/274 (0%) 2/275 (0.7%) 2/272 (0.7%)
    Mitral valve incompetence 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Myocardial infarction 5/274 (1.8%) 1/274 (0.4%) 0/275 (0%) 3/272 (1.1%)
    Pericardial effusion 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Sick sinus syndrome 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 1/272 (0.4%)
    Sinus arrest 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Tachyarrhythmia 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Ventricular fibrillation 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Ventricular tachycardia 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Ear and labyrinth disorders
    Vertigo 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Eye disorders
    Age-related macular degeneration 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Corneal oedema 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Iridocyclitis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Macular degeneration 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Macular hole 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Retinal artery occlusion 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Retinal haemorrhage 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 1/272 (0.4%)
    Retinal tear 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Retinal vein occlusion 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Visual acuity reduced 0/274 (0%) 3/274 (1.1%) 2/275 (0.7%) 0/272 (0%)
    Vitreous floaters 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Visual acuity reduced 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Gastrointestinal disorders
    Abdominal adhesions 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Abdominal pain 1/274 (0.4%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Colitis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Diarrhoea 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Gastric antral vascular ectasia 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Gastric ulcer haemorrhage 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Gastritis 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Gastrointestinal haemorrhage 2/274 (0.7%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Haematochezia 0/274 (0%) 0/274 (0%) 0/275 (0%) 2/272 (0.7%)
    Ileus 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Inguinal hernia 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Intestinal obstruction 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 1/272 (0.4%)
    Large intestinal harmorrhage 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Pancreatic mass 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Small intestinal obstruction 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    General disorders
    Asthenia 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Chest pain 2/274 (0.7%) 0/274 (0%) 2/275 (0.7%) 0/272 (0%)
    Death 2/274 (0.7%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Device dislocation 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Device failure 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Medical device complication 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Non-cardiac chest pain 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Oedema peripheral 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Pain 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Ulcer haemorrhage 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Cholangitis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Cholecystitis acute 1/274 (0.4%) 0/274 (0%) 1/275 (0.4%) 1/272 (0.4%)
    Cholelithiasis 2/274 (0.7%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Gallbladder pain 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Infections and infestations
    Appendicitis perforated 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Bacterial sepsis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Brain abscess 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Breast infection 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Bronchitis 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Cellulitis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Clostridium difficile colitis 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Diverticulitis 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Empyema 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Endocarditis bacterial 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Endophthalmitis 2/274 (0.7%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Lobar pneumonia 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 1/272 (0.4%)
    Lung abscess 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Pneumonia 5/274 (1.8%) 5/274 (1.8%) 6/275 (2.2%) 3/272 (1.1%)
    Pyelonephritis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Sepsis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 1/272 (0.4%)
    Septic shock 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Urinary tract infection 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Endophthalmitis 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 2/272 (0.7%)
    Cystitis radiation 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Facial bones fracture 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Fall 1/274 (0.4%) 2/274 (0.7%) 1/275 (0.4%) 3/272 (1.1%)
    Hip fracture 1/274 (0.4%) 1/274 (0.4%) 3/275 (1.1%) 3/272 (1.1%)
    Joint dislocation 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 1/272 (0.4%)
    Joint sprain 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Overdose 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Pelvic fracture 0/274 (0%) 0/274 (0%) 2/275 (0.7%) 0/272 (0%)
    Post procedural complication 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Post procedural heamatoma 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Procedural hypertension 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Road traffic accident 1/274 (0.4%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Splenic injury 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Splenic rupture 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Thoracic vertebral fracture 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Upper limb fracture 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Wrist fracture 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Investigations
    Blood creatinine increased 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Haemoglobin decreased 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Urine output decreased 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Metabolism and nutrition disorders
    Dehydration 3/274 (1.1%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Hyperkalaemia 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Hyponatraemia 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Hypovolaemia 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/274 (0%) 2/274 (0.7%) 0/275 (0%) 1/272 (0.4%)
    Arthritis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 2/272 (0.7%)
    Back pain 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Bone pain 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Foot deformity 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Intervertebral disc degeneration 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Lumbar spinal stenosis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Osteoarthritis 0/274 (0%) 0/274 (0%) 3/275 (1.1%) 0/272 (0%)
    Osteonecrosis 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Spinal column stenosis 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Spondylolisthesis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Breast cancer 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Bronchial carcinoma 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Colon adenoma 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Endometrial cancer 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Gallbladder cancer 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Hepatic neoplasm malignant 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Lipoma 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Lung adenocarcinoma recurrent 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Lung cancer metastatic 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Lung carcinoma cell type unspecified recurrent 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Lung neoplasm malignant 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Metastases to lung 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Non-Hodgkin's lymphoma 1/274 (0.4%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Non-Hodgkin's lymphoma recurrent 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Oesophageal carcinoma 1/274 (0.4%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Pancreatic carcinoma 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Renal cell carcinoma 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Skin cancer 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Small cell carcinoma 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Small cell lung cancer metastatic 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Small cell lung cancer stage unspecified 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Splenic marginal zone lymphoma 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Tumour ulceration 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Nervous system disorders
    Carotid artery stenosis 0/274 (0%) 0/274 (0%) 0/275 (0%) 2/272 (0.7%)
    Cerebrovascular accident 2/274 (0.7%) 1/274 (0.4%) 2/275 (0.7%) 2/272 (0.7%)
    Cervicobrachial syndrome 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Convulsion 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Dementia 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Embolic stroke 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Hypoaesthesia 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Hypoxic-ischaemic encephalopathy 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Ischaemic stroke 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Loss of consciousness 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Nerve compression 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Paraparesis 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Presyncope 1/274 (0.4%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Syncope 2/274 (0.7%) 2/274 (0.7%) 1/275 (0.4%) 1/272 (0.4%)
    Transient ischaemic attack 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Psychiatric disorders
    Anxiety 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Depression 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Hallucination 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Mental status changes 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Somatic delusion 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Renal and urinary disorders
    Cystitis haemorrhagic 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Nephrolithiasis 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Renal artery stenosis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Renal failure 1/274 (0.4%) 1/274 (0.4%) 2/275 (0.7%) 2/272 (0.7%)
    Renal failure chronic 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Renal impairment 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Reproductive system and breast disorders
    Uterine haemorrhage 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Uterovaginal prolapse 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Acute respiratory failure 1/274 (0.4%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Asthma 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Bronchospasm 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Chronic obstructive pulmonary disease 2/274 (0.7%) 0/274 (0%) 1/275 (0.4%) 4/272 (1.5%)
    Dyspnoea 1/274 (0.4%) 1/274 (0.4%) 0/275 (0%) 1/272 (0.4%)
    Idiopathic pulmonary fibrosis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Nasal polyps 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Pleural effusion 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Pneumonitis 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Pneumothorax 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Pulmonary embolism 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Respiratory arrest 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Respiratory failure 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Surgical and medical procedures
    Thrombosis prophylaxis 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Vascular disorders
    Aortic aneurysm 1/274 (0.4%) 1/274 (0.4%) 2/275 (0.7%) 1/272 (0.4%)
    Deep vein thrombosis 0/274 (0%) 1/274 (0.4%) 1/275 (0.4%) 0/272 (0%)
    Haemorrhage 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Hypertension 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 1/272 (0.4%)
    Hypertensive crisis 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Peripheral arterial occlusive disease 0/274 (0%) 0/274 (0%) 0/275 (0%) 1/272 (0.4%)
    Peripheral embolism 0/274 (0%) 0/274 (0%) 1/275 (0.4%) 0/272 (0%)
    Shock haemorrhagic 0/274 (0%) 1/274 (0.4%) 0/275 (0%) 0/272 (0%)
    Thrombophlebitis 1/274 (0.4%) 0/274 (0%) 0/275 (0%) 0/272 (0%)
    Other (Not Including Serious) Adverse Events
    Ranibizumab 0.5 mg Monthly Ranibizumab 2.0 mg Monthly Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 240/274 (87.6%) 243/274 (88.7%) 250/275 (90.9%) 239/272 (87.9%)
    Eye disorders
    Age-related macular degeneration 8/274 (2.9%) 15/274 (5.5%) 15/275 (5.5%) 13/272 (4.8%)
    Conjunctival haemorrhage 63/274 (23%) 51/274 (18.6%) 48/275 (17.5%) 41/272 (15.1%)
    Detachment of retinal pigment epithelium 4/274 (1.5%) 4/274 (1.5%) 17/275 (6.2%) 11/272 (4%)
    Eye pain 15/274 (5.5%) 25/274 (9.1%) 16/275 (5.8%) 23/272 (8.5%)
    Macular degeneration 12/274 (4.4%) 8/274 (2.9%) 18/275 (6.5%) 15/272 (5.5%)
    Retinal haemorrhage 6/274 (2.2%) 7/274 (2.6%) 14/275 (5.1%) 12/272 (4.4%)
    Vitreous detachment 22/274 (8%) 21/274 (7.7%) 16/275 (5.8%) 27/272 (9.9%)
    Vitreous floaters 26/274 (9.5%) 15/274 (5.5%) 11/275 (4%) 17/272 (6.3%)
    Macular degeneration 14/274 (5.1%) 12/274 (4.4%) 11/275 (4%) 14/272 (5.1%)
    Retinal haemorrhage 12/274 (4.4%) 15/274 (5.5%) 6/275 (2.2%) 12/272 (4.4%)
    Vitreous detachment 20/274 (7.3%) 24/274 (8.8%) 17/275 (6.2%) 13/272 (4.8%)
    Infections and infestations
    Nasopharyngitis 17/274 (6.2%) 10/274 (3.6%) 17/275 (6.2%) 23/272 (8.5%)
    Sinusitis 12/274 (4.4%) 7/274 (2.6%) 27/275 (9.8%) 8/272 (2.9%)
    Urinary tract infection 15/274 (5.5%) 14/274 (5.1%) 17/275 (6.2%) 16/272 (5.9%)
    Injury, poisoning and procedural complications
    Fall 14/274 (5.1%) 12/274 (4.4%) 8/275 (2.9%) 21/272 (7.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/274 (1.8%) 10/274 (3.6%) 6/275 (2.2%) 14/272 (5.1%)
    Vascular disorders
    Hypertension 14/274 (5.1%) 20/274 (7.3%) 21/275 (7.6%) 15/272 (5.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Genentech, Inc.
    Phone 800-821-8590
    Email
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT00891735
    Other Study ID Numbers:
    • FVF4579g
    • GX01511
    First Posted:
    May 1, 2009
    Last Update Posted:
    Jan 18, 2013
    Last Verified:
    Dec 1, 2012