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Blossom: Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Branch Retinal Vein Occlusion (BRVO)

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01976338
Collaborator
(none)
283
Enrollment
33
Locations
2
Arms
28.5
Actual Duration (Months)
8.6
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Provided efficacy and safety data on intravitreal injections of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to BRVO

Condition or Disease Intervention/Treatment Phase
  • Drug: Ranibizumab 0.5 mg
  • Other: Sham injection
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
283 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized Double-masked, Phase III Study Assessing Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Visual Impairment Due to Macular Edema (ME) Secondary to Branch Retinal Vein Occlusion (BRVO) [Blossom]
Actual Study Start Date :
Nov 12, 2013
Actual Primary Completion Date :
Mar 28, 2016
Actual Study Completion Date :
Mar 28, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ranibizumab 0.5 mg

PRN Intravitreal injection

Drug: Ranibizumab 0.5 mg
intravitreal injection of 0.05 ml
Sham Comparator: Sham injection

As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection

Other: Sham injection
Sham intravitreal injection
Other Names:
  • Sham

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6 [Baseline to Month 1 through Month 6]

      Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 6 and compared to Baseline.

    Secondary Outcome Measures

    1. Average Change of Best Corrected Visual Acuity (BCVA) in Patients From Baseline to Month 1 Through Month 12 [Baseline to Month 1 through Month 12]

      Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline

    2. Best Corrected Visual Acuity (BCVA) Change Over Time [Month 1 through Month 12]

      Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline

    3. Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time [Baseline to month 12]

      Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters

    4. Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye [Baseline to 12 months]

      Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.

    5. Change in Central-Sub-Field- Thickness (CSFT) Over Time [Month 1 to month 12]

      OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center

    6. Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time [month 3, 6 and 12]

      Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

    7. Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time [Months 3, 6 and 12]

      Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

    8. Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time [Months 3, 6 and 12]

      Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

    9. Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12 [Baseline, months 3, 6 and 12]

      The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with visual impairment secondary to branch retinal vein occlusion (BRVO) with a BCVA between 19 and 73 letters in one eye and at least 35 letters in the other eye.

    Exclusion Criteria:

    • Pregnant or nursing women or women of child bearing potential without unless using an effective contraception

    • Stroke or myocard infarction within 3 months prior to study

    • History of malignancy within the past 5 years

    • Uncontrolled hypertension

    • Active infection or inflammation in any eye

    • use of corticosteroids for at least 30 days in the last 6 months

    • treatment with anti-angiogenic drugs in any eye within last 3 months

    • Panretinal or focal/drid laser photocoagulation within the last few months

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Beijing Beijing China 100191
    2 Novartis Investigative Site Beijing Beijing China 100730
    3 Novartis Investigative Site Chongqing Chongqing China 400042
    4 Novartis Investigative Site Guangzhou Guangdong China 510060
    5 Novartis Investigative Site Shantou Guangdong China 515041
    6 Novartis Investigative Site Harbin Heilongjiang China 150001
    7 Novartis Investigative Site Wuhan Hubei China 430070
    8 Novartis Investigative Site Changsha Hunan China 410011
    9 Novartis Investigative Site Nanjing Jiangsu China 210006
    10 Novartis Investigative Site Nanjing Jiangsu China 210029
    11 Novartis Investigative Site Nantong Jiangsu China 226000
    12 Novartis Investigative Site Nanchang Jiangxi China 330006
    13 Novartis Investigative Site Qingdao Shandong China 266011
    14 Novartis Investigative Site Chengdu Sichuan China 610041
    15 Novartis Investigative Site Tianjin Tianjin China 300020
    16 Novartis Investigative Site Tianjin Tianjin China 300070
    17 Novartis Investigative Site Wenzhou Zhejiang China 325027
    18 Novartis Investigative Site Beijing China 100034
    19 Novartis Investigative Site Beijing China 100176
    20 Novartis Investigative Site Beijing China 100730
    21 Novartis Investigative Site Chongqing China 400038
    22 Novartis Investigative Site Shanghai China 200080
    23 Novartis Investigative Site Shanghai China 200092
    24 Novartis Investigative Site Hongkong Hong Kong
    25 Novartis Investigative Site Bandung Jawa Barat Indonesia 40117
    26 Novartis Investigative Site Jakarta Indonesia 10430
    27 Novartis Investigative Site Manila Metro Manila Philippines 1000
    28 Novartis Investigative Site San Juan City Philippines 1500
    29 Novartis Investigative Site Kaohsiung Taiwan 83301
    30 Novartis Investigative Site Lin-Kou Taiwan 33305
    31 Novartis Investigative Site Taipei Taiwan
    32 Novartis Investigative Site Hanoi Vietnam 10000
    33 Novartis Investigative Site Ho Chi Minh City Vietnam 70000

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01976338
    Other Study ID Numbers:
    • CRFB002E2303
    First Posted:
    Nov 5, 2013
    Last Update Posted:
    May 8, 2017
    Last Verified:
    Mar 1, 2017
    Keywords provided by Novartis Pharmaceuticals
    BRVO
    macular edema
    vision impairment
    retinal vein occlusion
    ranibizumab
    branch retinal vein occlusion
    anti-VEGF therapy
    RFB002
    Additional relevant MeSH terms:
    Neoplasm Metastasis
    Macular Edema
    Retinal Vein Occlusion
    Edema
    Ranibizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This study consisted of the following three periods (Screening period: Day -14 to Day -1; treatment period: Day 1 to Month 11; post-treatment Follow-Up period: Month 11 to Month 12). At Baseline (Visit 2, Day 1), eligible patients were randomized in a 2:1 ratio into respective treatment arms
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Period Title: Overall Study
    STARTED 190 93
    Completed 6 Months 185 91
    Discontinued Study Prior to 6 Months 5 2
    COMPLETED 177 89
    NOT COMPLETED 13 4

    Baseline Characteristics

    Arm/Group Title Ranibizumab 0.5 mg Sham Injection Total
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection Total of all reporting groups
    Overall Participants 190 93 283
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    57.0
    (10.14)
    56.8
    (10.03)
    56.9
    (10.09)
    Sex: Female, Male (Count of Participants)
    Female
    101
    53.2%
    38
    40.9%
    139
    49.1%
    Male
    89
    46.8%
    55
    59.1%
    144
    50.9%

    Outcome Measures

    1. Primary Outcome
    Title Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6
    Description Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 6 and compared to Baseline.
    Time Frame Baseline to Month 1 through Month 6

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 189 93
    Mean (Standard Deviation) [Letters]
    12.5
    (8.34)
    5.0
    (9.18)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5 mg, Sham Injection
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    2. Secondary Outcome
    Title Average Change of Best Corrected Visual Acuity (BCVA) in Patients From Baseline to Month 1 Through Month 12
    Description Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline
    Time Frame Baseline to Month 1 through Month 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 189 93
    Mean (Standard Deviation) [Letters]
    14.0
    (8.99)
    7.7
    (9.41)
    3. Secondary Outcome
    Title Best Corrected Visual Acuity (BCVA) Change Over Time
    Description Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline
    Time Frame Month 1 through Month 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 189 93
    Month 1
    9.5
    (8.26)
    1.7
    (8.70)
    Month 2
    11.7
    (8.39)
    3.7
    (8.81)
    Month 3
    12.9
    (8.81)
    5.1
    (10.10)
    Month 4
    13.4
    (9.72)
    6.0
    (10.44)
    Month 5
    13.6
    (10.24)
    6.5
    (11.53)
    Month 6
    14.0
    (10.75)
    7.0
    (12.75)
    Month 7
    14.7
    (10.62)
    8.5
    (10.97)
    Month 8
    14.9
    (10.52)
    10.4
    (10.97)
    Month 9
    14.8
    (10.43)
    10.3
    (10.78)
    Month 10
    15.8
    (10.67)
    11.2
    (11.12)
    Month 11
    15.8
    (10.42)
    11.1
    (10.48)
    Month 12
    16.4
    (10.95)
    11.3
    (11.11)
    4. Secondary Outcome
    Title Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time
    Description Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters
    Time Frame Baseline to month 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 190 93
    Month 1 Gain of >=5 letters
    139
    73.2%
    33
    35.5%
    Month 1 Gain of >=10 letters
    86
    45.3%
    12
    12.9%
    Month 1 Gain of >=15 letters
    43
    22.6%
    3
    3.2%
    Month 1 Gain of >=30 letters
    2
    1.1%
    0
    0%
    Month 2 Gain of >=5 letters
    156
    82.1%
    44
    47.3%
    Month 2 Gain of >=10 letters
    113
    59.5%
    21
    22.6%
    Month 2 Gain of >=15 letters
    72
    37.9%
    6
    6.5%
    Month 2 Gain of >=30 letters
    6
    3.2%
    2
    2.2%
    Month 3 Gain of >=5 letters
    162
    85.3%
    49
    52.7%
    Month 3 Gain of >=10 letters
    116
    61.1%
    29
    31.2%
    Month 3 Gain of >=15 letters
    76
    40%
    16
    17.2%
    Month 3 Gain of >=30 letters
    8
    4.2%
    0
    0%
    Month 4 Gain of >=5 letters
    159
    83.7%
    55
    59.1%
    Month 4 Gain of >=10 letters
    122
    64.2%
    32
    34.4%
    Month 4 Gain of >=15 letters
    83
    43.7%
    16
    17.2%
    Month 4 Gain of >=30 letters
    11
    5.8%
    2
    2.2%
    Month 5 Gain of >=5 letters
    159
    83.7%
    60
    64.5%
    Month 5 Gain of >=10 letters
    127
    66.8%
    40
    43%
    Month 5 Gain of >=15 letters
    83
    43.7%
    19
    20.4%
    Month 5 Gain of >=30 letters
    15
    7.9%
    2
    2.2%
    Month 6 Gain of >=5 letters
    163
    85.8%
    58
    62.4%
    Month 6 Gain of >=10 letters
    129
    67.9%
    47
    50.5%
    Month 6 Gain of >=15 letters
    88
    46.3%
    25
    26.9%
    Month 6 Gain of >=30 letters
    16
    8.4%
    3
    3.2%
    Month 7 Gain of >=5 letters
    162
    85.3%
    63
    67.7%
    Month 7 Gain of >=10 letters
    135
    71.1%
    49
    52.7%
    Month 7 Gain of >=15 letters
    93
    48.9%
    28
    30.1%
    Month 7 Gain of >=30 letters
    16
    8.4%
    3
    3.2%
    Month 8 Gain of >=5 letters
    168
    88.4%
    66
    71%
    Month 8 Gain of >=150 letters
    130
    68.4%
    52
    55.9%
    Month 8 Gain of >=15 letters
    94
    49.5%
    33
    35.5%
    Month 8 Gain of >=30 letters
    17
    8.9%
    4
    4.3%
    Month 9 Gain of >=5 letters
    163
    85.8%
    67
    72%
    Month 9 Gain of >=10 letters
    139
    73.2%
    52
    55.9%
    Month 9 Gain of >=15 letters
    90
    47.4%
    32
    34.4%
    Month 9 Gain of >=30 letters
    17
    8.9%
    4
    4.3%
    Month 10 Gain of >=5 letters
    169
    88.9%
    68
    73.1%
    Month 10 Gain of >=10 letters
    143
    75.3%
    53
    57%
    Month 10 Gain of >=15 letters
    97
    51.1%
    37
    39.8%
    Month 10 Gain of >=30 letters
    22
    11.6%
    7
    7.5%
    Month 11 Gain of >=5 letters
    172
    90.5%
    67
    72%
    Month 11 Gain of >=10 letters
    141
    74.2%
    56
    60.2%
    Month 11 Gain of >=15 letters
    103
    54.2%
    36
    38.7%
    Month 11 Gain of >=30 letters
    19
    10%
    4
    4.3%
    Month 12 Gain of >=5 letters
    171
    90%
    72
    77.4%
    Month 12 Gain of >=10 letters
    142
    74.7%
    56
    60.2%
    Month 12 Gain of >=15 letters
    105
    55.3%
    36
    38.7%
    Month 12 Gain of >=30 letters
    24
    12.6%
    5
    5.4%
    5. Secondary Outcome
    Title Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye
    Description Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.
    Time Frame Baseline to 12 months

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 190 93
    Month 1, Loss of < 15 letters
    188
    98.9%
    89
    95.7%
    Month 2, Loss of < 15 letters
    189
    99.5%
    90
    96.8%
    Month 3, Loss of < 15 letters
    189
    99.5%
    88
    94.6%
    Month 4, Loss of < 15 letters
    189
    99.5%
    88
    94.6%
    Month 5, Loss of < 15 letters
    189
    99.5%
    88
    94.6%
    Month 6, Loss of < 15 letters
    188
    98.9%
    89
    95.7%
    Month 7, Loss of < 15 letters
    188
    98.9%
    91
    97.8%
    Month 8, Loss of < 15 letters
    188
    98.9%
    92
    98.9%
    Month 9, Loss of < 15 letters
    187
    98.4%
    93
    100%
    Month 10, Loss of < 15 letters
    188
    98.9%
    92
    98.9%
    Month 11, Loss of < 15 letters
    187
    98.4%
    93
    100%
    Month 12, Loss of < 15 letters
    187
    98.4%
    91
    97.8%
    6. Secondary Outcome
    Title Change in Central-Sub-Field- Thickness (CSFT) Over Time
    Description OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center
    Time Frame Month 1 to month 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 188 93
    Month 1
    -261.1
    (171.95)
    -42.4
    (171.88)
    Month 2
    -274.8
    (174.17)
    -93.1
    (187.14)
    Month 3
    -282.2
    (175.86)
    -155.3
    (209.37)
    Month 4
    -254.7
    (183.87)
    -193.2
    (221.58)
    Month 5
    -258.6
    (180.57)
    -203.2
    (218.02)
    Month 6
    -264.1
    (168.64)
    -206.6
    (221.85)
    Month 7
    -265.4
    (179.06)
    -289.8
    (228.03)
    Month 8
    -263.8
    (179.38)
    -286.1
    (236.75)
    Month 9
    -266.7
    (182.60)
    -287.9
    (237.61)
    Month 10
    -268.4
    (173.71)
    -282.9
    (239.98)
    Month 11
    -270.6
    (184.34)
    -290.3
    (227.47)
    Month 12
    -273.4
    (184.33)
    -282.9
    (233.69)
    7. Secondary Outcome
    Title Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time
    Description Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
    Time Frame month 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 186 90
    Month 3
    -0.400
    (0.3576)
    -0.026
    (0.3387)
    Month 6
    -0.356
    (0.3983)
    -0.055
    (0.4060)
    Month 12
    -0.391
    (0.3716)
    -.0208
    (0.4075)
    8. Secondary Outcome
    Title Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time
    Description Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
    Time Frame Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 186 90
    Month 3
    -1.869
    (1.8071)
    0.111
    (1.5497)
    Month 6
    -1.642
    (1.9570)
    -0.078
    (1.6856)
    Month 12
    -1.732
    (1.8059)
    -0.823
    (1.9650)
    9. Secondary Outcome
    Title Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time
    Description Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
    Time Frame Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 186 90
    Month 3
    -4.994
    (5.4066)
    -0.600
    (3.6646)
    Month 6
    -4.654
    (5.7504)
    -0.836
    (4.2819)
    Month 12
    -5.078
    (5.9568)
    -2.797
    (5.3702)
    10. Secondary Outcome
    Title Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12
    Description The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.
    Time Frame Baseline, months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. n=the number of patients with a value for both baseline and the specific post-baseline visit.
    Arm/Group Title Ranibizumab 0.5 mg Sham Injection
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
    Measure Participants 190 93
    Change from Baseline at M3 (n=187,91)
    5.8
    (10.85)
    -1.1
    (11.21)
    Change from Baseline at M6 (n=185,88)
    7.7
    (11.88)
    0.1
    (13.95)
    Change from Baseline at M12 (n=176,88)
    9.6
    (13.45)
    3.3
    (13.52)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
    Arm/Group Title Ranibizumab 0.5 mg Sham With Ranibizumab 0.5 mg Sham Without Ranibizumab 0.5 mg
    Arm/Group Description PRN Intravitreal injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection sham + ranibizumab 0.5 mg PRN as of Month 6 (hereafter referred to as sham group up to Month 6 and sham with ranibizumab or sham without ranibizumab after Month 6)
    All Cause Mortality
    Ranibizumab 0.5 mg Sham With Ranibizumab 0.5 mg Sham Without Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ranibizumab 0.5 mg Sham With Ranibizumab 0.5 mg Sham Without Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/190 (6.8%) 3/66 (4.5%) 3/26 (11.5%)
    Cardiac disorders
    Atrial fibrillation 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Cardiac failure 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Cardiac valve disease 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Coronary artery disease 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Endocrine disorders
    Hyperthyroidism 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Eye disorders
    Cataract 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Macular hole 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Gastrointestinal disorders
    Colitis ulcerative 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Hepatobiliary disorders
    Cholecystitis chronic 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Infections and infestations
    Pneumonia 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Injury, poisoning and procedural complications
    Clavicle fracture 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Contusion 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Fibula fracture 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Humerus fracture 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Joint dislocation 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Lower limb fracture 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Post concussion syndrome 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Tibia fracture 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Ulna fracture 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Intervertebral disc protrusion 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Synovial cyst 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Nervous system disorders
    Cluster headache 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Transient ischaemic attack 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Vertebrobasilar insufficiency 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary fibrosis 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Vascular disorders
    Haematoma 1/190 (0.5%) 0/66 (0%) 0/26 (0%)
    Hypertension 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Other (Not Including Serious) Adverse Events
    Ranibizumab 0.5 mg Sham With Ranibizumab 0.5 mg Sham Without Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 119/190 (62.6%) 46/66 (69.7%) 14/26 (53.8%)
    Blood and lymphatic system disorders
    Anaemia 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Leukocytosis 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Cardiac disorders
    Angina pectoris 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Arteriosclerosis coronary artery 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Coronary artery disease 4/190 (2.1%) 0/66 (0%) 0/26 (0%)
    Eye disorders
    Age-related macular degeneration 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Angle closure glaucoma 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Cataract 2/190 (1.1%) 1/66 (1.5%) 0/26 (0%)
    Conjunctival deposit 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Conjunctival haemorrhage 20/190 (10.5%) 4/66 (6.1%) 0/26 (0%)
    Conjunctivitis allergic 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Corneal epithelium defect 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Dry eye 3/190 (1.6%) 0/66 (0%) 1/26 (3.8%)
    Eye irritation 1/190 (0.5%) 2/66 (3%) 0/26 (0%)
    Eye pain 10/190 (5.3%) 1/66 (1.5%) 0/26 (0%)
    Eye pruritus 4/190 (2.1%) 1/66 (1.5%) 0/26 (0%)
    Eye swelling 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Eyelid oedema 1/190 (0.5%) 1/66 (1.5%) 1/26 (3.8%)
    Foreign body sensation in eyes 6/190 (3.2%) 1/66 (1.5%) 1/26 (3.8%)
    Glare 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Keratitis 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Lacrimation increased 0/190 (0%) 2/66 (3%) 0/26 (0%)
    Macular fibrosis 6/190 (3.2%) 1/66 (1.5%) 0/26 (0%)
    Ocular hyperaemia 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Ocular hypertension 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Open angle glaucoma 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Retinal fibrosis 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Retinal haemorrhage 3/190 (1.6%) 3/66 (4.5%) 0/26 (0%)
    Retinal ischaemia 7/190 (3.7%) 3/66 (4.5%) 1/26 (3.8%)
    Retinal neovascularisation 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Retinal vein occlusion 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Vision blurred 3/190 (1.6%) 2/66 (3%) 0/26 (0%)
    Visual acuity reduced 1/190 (0.5%) 2/66 (3%) 0/26 (0%)
    Vitreous detachment 3/190 (1.6%) 1/66 (1.5%) 0/26 (0%)
    Vitreous floaters 4/190 (2.1%) 2/66 (3%) 0/26 (0%)
    Vitreous haemorrhage 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Vitreous opacities 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/190 (0.5%) 1/66 (1.5%) 1/26 (3.8%)
    Abdominal pain upper 2/190 (1.1%) 0/66 (0%) 1/26 (3.8%)
    Chronic gastritis 3/190 (1.6%) 1/66 (1.5%) 0/26 (0%)
    Diarrhoea 4/190 (2.1%) 1/66 (1.5%) 0/26 (0%)
    Gastritis 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Gastrooesophageal reflux disease 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Mouth ulceration 1/190 (0.5%) 0/66 (0%) 1/26 (3.8%)
    Nausea 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Toothache 6/190 (3.2%) 2/66 (3%) 1/26 (3.8%)
    General disorders
    Peripheral swelling 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Pyrexia 2/190 (1.1%) 1/66 (1.5%) 0/26 (0%)
    Hepatobiliary disorders
    Hepatic function abnormal 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Infections and infestations
    Conjunctivitis 5/190 (2.6%) 1/66 (1.5%) 1/26 (3.8%)
    Gingivitis 0/190 (0%) 2/66 (3%) 0/26 (0%)
    Nasopharyngitis 23/190 (12.1%) 8/66 (12.1%) 3/26 (11.5%)
    Otitis media acute 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Periodontitis 1/190 (0.5%) 0/66 (0%) 1/26 (3.8%)
    Pharyngitis 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Tooth abscess 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Upper respiratory tract infection 10/190 (5.3%) 1/66 (1.5%) 1/26 (3.8%)
    Urinary tract infection 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Injury, poisoning and procedural complications
    Animal bite 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Conjunctival abrasion 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Ligament sprain 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Blood glucose increased 2/190 (1.1%) 1/66 (1.5%) 0/26 (0%)
    Blood pressure increased 3/190 (1.6%) 0/66 (0%) 0/26 (0%)
    Glucose urine present 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Haemoglobin urine present 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Hepatic enzyme increased 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Intraocular pressure increased 10/190 (5.3%) 1/66 (1.5%) 0/26 (0%)
    Optic nerve cup/disc ratio increased 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Platelet count decreased 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Platelet count increased 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Protein urine present 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Visual acuity tests abnormal 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Weight decreased 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 2/190 (1.1%) 0/66 (0%) 1/26 (3.8%)
    Gout 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Hyperlipidaemia 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Hypoglycaemia 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/190 (3.2%) 0/66 (0%) 0/26 (0%)
    Arthropathy 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Back pain 2/190 (1.1%) 0/66 (0%) 1/26 (3.8%)
    Fasciitis 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Gouty arthritis 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Pain in extremity 4/190 (2.1%) 0/66 (0%) 1/26 (3.8%)
    Spinal osteoarthritis 2/190 (1.1%) 0/66 (0%) 2/26 (7.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Meningioma 0/190 (0%) 0/66 (0%) 1/26 (3.8%)
    Nervous system disorders
    Balance disorder 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Dizziness 6/190 (3.2%) 2/66 (3%) 0/26 (0%)
    Headache 11/190 (5.8%) 2/66 (3%) 0/26 (0%)
    Syncope 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Psychiatric disorders
    Insomnia 1/190 (0.5%) 3/66 (4.5%) 0/26 (0%)
    Reproductive system and breast disorders
    Breast cyst 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 9/190 (4.7%) 2/66 (3%) 3/26 (11.5%)
    Oropharyngeal pain 4/190 (2.1%) 1/66 (1.5%) 0/26 (0%)
    Rhinitis allergic 0/190 (0%) 2/66 (3%) 0/26 (0%)
    Skin and subcutaneous tissue disorders
    Eczema 0/190 (0%) 1/66 (1.5%) 1/26 (3.8%)
    Rash 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Urticaria 1/190 (0.5%) 1/66 (1.5%) 0/26 (0%)
    Urticaria papular 0/190 (0%) 1/66 (1.5%) 0/26 (0%)
    Vascular disorders
    Aortic arteriosclerosis 2/190 (1.1%) 0/66 (0%) 0/26 (0%)
    Hypertension 16/190 (8.4%) 8/66 (12.1%) 4/26 (15.4%)

    Limitations/Caveats

    One patient was randomized to the ranibizumab group but received no study treatment during the study period and discontinued the study after Visit 2. Therefore, excluded from the Safety set

    More Information

    Certain Agreements

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

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01976338
    Other Study ID Numbers:
    • CRFB002E2303
    First Posted:
    Nov 5, 2013
    Last Update Posted:
    May 8, 2017
    Last Verified:
    Mar 1, 2017