Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 12-month, open-label, interventional, multicentre study to investigate the current criteria driving re-treatment with ranibizumab upon relapse in patients with visual impairment due to choroidal neovascularization secondary to pathologic myopia

    Summary
    EudraCT number
    		 2013-003334-33
    Trial protocol
    		 IT  
    Global end of trial date
    15 Jul 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Jul 2017
    First version publication date
    27 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CRFB002FIT01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02034006
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Jul 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jul 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to investigate current criteria driving retreatment in patients affected by CNV secondary to PM and experiencing a relapse of the disease after the first administration of ranibizumab. The criteria for retreatment may have consisted in patient subjectivity or in clinical findings following examination (BCVA, fundus), and/or optical coherence tomography (OCT), and/or fluorescein angiography (FAG).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. The investigator could prescribe any medication and/or supportive care during the study based on clinical needs.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jun 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 200
    Worldwide total number of subjects
    200
    EEA total number of subjects
    200
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    114
    From 65 to 84 years
    85
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Two hundred fifteen (215) subjects were screened in this study (i.e. provided written informed consent). Two hundred (200) subjects underwent baseline visit and received at least one injection of ranibizumab.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Ranibizumab
    Arm description
    		 Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ranibizumab
    Investigational medicinal product code
    RFB002
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Ocular use
    Dosage and administration details
    All patients received a single initial intravitreal injection of ranibizumab 0.5 mg/0.05 ml as per Committee for Human Medicinal Products (CHMP)approval. Further injections might have been required when monitoring reveals disease activity. Disease activity, defined as reduced visual acuity and/or signs of lesion activity, was evaluated based on clinical examination (BCVA, fundus), and/or optical coherence tomography (OCT), and/or fluorescein angiography (FAG). Bilateral treatment was allowed provided at least 14 days of intercurrence.

    Number of subjects in period 1
    		Ranibizumab
    Started
    200
    Once Treated Patients
    70 [1]
    Re-treated patients
    130 [2]
    Completed
    186
    Not completed
    14
         Adverse event, serious fatal
    1
         Consent withdrawn by subject
    7
         Pregnancy
    1
         Lost to follow-up
    5
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Out of total patients who took at least one ranibizumab injection, these patients received more than once.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Out of total patients who took at least one ranibizumab injection, these patients only received once.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ranibizumab
    Reporting group description
    		 Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.

    Reporting group values
    		 Ranibizumab Total
    Number of subjects
    		 200 200
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 61.82 ( 12.67 ) -
    Gender, Male/Female
    Units: Subjects
        Female
    		 53 53
        Male
    		 147 147

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Ranibizumab
    Reporting group description
    		 Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.

    Subject analysis set title
    Ranibizumab: Treated Once
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients treated only once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.

    Subject analysis set title
    Ranibizumab: Re-treated Once
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients treated more than once with a single ranibizumab 0.5 mg/0.05ml intravitreal injection.

    Primary: Number of patients treated and re-treated based on presence/absence of active leakage

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of active leakage
    End point description
    Presence of active leakage on fluorescein angiography (FAG) was assessed at screening (14 to 3 days before baseline visit), month 2 and month 6. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of active leakage (Yes/No). For retreated patients, the presence/absence of active leakage was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing Fluorescein angiography during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Screening: Active leakage, No (n= 64, 124)
    3
    0
        Screening: Active leakage, Yes (n= 64, 124)
    61
    121
        Screening: Active leakage, NE (n= 64, 124)
    0
    2
        Screening: Active leakage, Missing (n= 64, 124)
    0
    1
        Month 2: Active leakage, No (n= 61, 119)
    58
    61
        Month 2: Active leakage, Yes (n= 61, 119)
    3
    56
        Month 2: Active leakage, NE (n= 61, 119)
    0
    2
        Month 6: Active leakage, No (n= 60, 115)
    55
    73
        Month 6: Active leakage, Yes (n= 60, 115)
    4
    40
        Month 6: Active leakage, NE (n= 60, 115)
    1
    2
    Statistical analysis title
    		 Presence vs. absence of active leakage
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    72.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.44
         upper limit
    		 223.42

    Primary: Number of patients treated and re-treated based on presence/absence of macular edema

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of macular edema
    End point description
    Presence of macular edema from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of macular edema (Yes/No). For retreated patients, the presence/absence of macular edema was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Screening: Macular Edema, No (n= 69, 129)
    38
    63
        Screening: Macular Edema, Yes (n= 69, 129)
    28
    65
        Screening: Macular Edema, NE (n= 69, 129)
    3
    1
        Month 2: Macular Edema, No (n= 63, 129)
    59
    103
        Month 2: Macular Edema, Yes (n= 63, 129)
    3
    24
        Month 2: Macular Edema, NE (n= 63, 129)
    1
    2
        Month 6: Macular Edema, No (n= 60, 126)
    57
    101
        Month 6: Macular Edema, Yes (n= 60, 126)
    2
    24
        Month 6: Macular Edema, NE(n= 60, 126)
    1
    1
        Month 12: Macular Edema, No (n= 61, 124)
    56
    108
        Month 12: Macular Edema, Yes (n= 61, 124)
    4
    15
        Month 12: Macular Edema, NE (n= 61, 124)
    1
    1
    Statistical analysis title
    		 Presence vs. absence of macular edema
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    9.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.18
         upper limit
    		 27.36

    Primary: Number of patients treated and re-treated based on presence/absence of cysts

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of cysts
    End point description
    Presence of cysts from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of cysts (Yes/No). For retreated patients, the presence/absence of cysts was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Screening: Cysts, No (n= 69, 129)
    41
    79
        Screening: Cysts, Yes (n= 69, 129)
    27
    50
        Screening: Cysts, NE (n= 69, 129)
    1
    0
        Month 2: Cysts, No (n= 63, 129)
    60
    94
        Month 2: Cysts, Yes (n= 63, 129)
    2
    32
        Month 2: Cysts, NE (n= 63, 129)
    1
    2
        Month 2: Cysts, Missing (n= 63, 129)
    0
    1
        Month 6: Cysts, No (n= 60, 126)
    57
    98
        Month 6: Cysts, Yes (n= 60, 126)
    2
    27
        Month 6: Cysts, NE(n= 60, 126)
    1
    1
        Month 12: Cysts, No (n= 61, 124)
    57
    97
        Month 12: Cysts, Yes (n= 61, 124)
    3
    26
        Month 12: Cysts, NE (n= 61, 124)
    1
    1
    Statistical analysis title
    		 Presence vs. absence of cysts
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    12.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.76
         upper limit
    		 42.67

    Primary: Number of patients treated and re-treated based on presence/absence of Intra-retinal fluid

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of Intra-retinal fluid
    End point description
    Presence of Intra-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of Intra-retinal fluid (Yes/No). For retreated patients, the presence/absence of Intra-retinal fluid was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Screening: Intra-retinal fluid, No (n= 69, 129)
    19
    37
        Screening: Intra-retinal fluid, Yes (n= 69, 129)
    49
    90
        Screening: Intra-retinal fluid, NE (n= 69, 129)
    1
    2
        Month 2: Intra-retinal fluid, No (n= 63, 129)
    55
    77
        Month 2: Intra-retinal fluid, Yes (n= 63, 129)
    7
    50
        Month 2: Intra-retinal fluid, NE (n= 63, 129)
    1
    2
        Month 6: Intra-retinal fluid, No (n= 60, 126)
    57
    85
        Month 6: Intra-retinal fluid, Yes (n= 60, 126)
    1
    38
        Month 6: Intra-retinal fluid, NE(n= 60, 126)
    2
    3
        Month 12: Intra-retinal fluid, No (n= 61, 124)
    58
    96
        Month 12: Intra-retinal fluid, Yes (n= 61, 124)
    2
    26
        Month 12: Intra-retinal fluid, NE (n= 61, 124)
    1
    2
    Statistical analysis title
    		 Presence vs. absence of intra-retinal fluid
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    49.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.62
         upper limit
    		 213.5

    Primary: Change in Central subfield thickness (CSFT)

    		 Close Top of page
    End point title
    		 Change in Central subfield thickness (CSFT)
    End point description
    Central subfield thickness (CSFT) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSFT versus previous visit. For retreated patients, the change in CSFT was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: micromilimeter(um)
    arithmetic mean (standard deviation)
        Month 2 Vs. Screening : CSFT (n= 61, 125)
    -16.15 ( 86.65 )
    -34.28 ( 78.01 )
        Month 6 Vs. Month 2: CSFT (n= 57, 121)
    -11.04 ( 61.06 )
    -15.83 ( 70.74 )
        Month 12 Vs. Month 6: CSFT (n= 57, 119)
    1.29 ( 62.55 )
    8.64 ( 76.79 )
    Statistical analysis title
    		 Change in CST vs previous vist
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1514
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1

    Primary: Change in Central subfield volume (CSV)

    		 Close Top of page
    End point title
    		 Change in Central subfield volume (CSV)
    End point description
    Central subfield volume (CSV) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSV versus previous visit. For retreated patients, the change in CSV was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. *NE = Not evaluable Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: mm^3
    arithmetic mean (standard deviation)
        Month 2 Vs. Screening : CSV (n= 49, 96)
    -0.02 ( 0.06 )
    -0.02 ( 0.06 )
        Month 6 Vs. Month 2: CSV (n= 48, 97)
    0 ( 0.04 )
    -0.01 ( 0.07 )
        Month 12 Vs. Month 6: CSV (n= 49, 101)
    0 ( 0.04 )
    0.01 ( 0.08 )
    Statistical analysis title
    		 Change in Central subfield volume vs previous vist
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1265
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 5.63

    Primary: Number of patients treated and re-treated based on presence/absence of sub-retinal fluid

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of sub-retinal fluid [1]
    End point description
    Presence of sub-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. The regression model for sub-retinal fluid was not valid because “Yes” was reported in almost all subjects causing a quasi-complete separation of data points. *NE = Not Evaluable Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing OCT during that time point.
    End point type
    Primary
    End point timeframe
    Screening, Month 2, Month 6, Month 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The regression model for sub-retinal fluid was not valid hence no analysis.
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Screening: Sub-retinal fluid, No (n= 69, 129)
    43
    65
        Screening: Sub-retinal fluid, Yes (n= 69, 129)
    25
    61
        Screening: Sub-retinal fluid, NE (n= 69, 129)
    1
    3
        Month 2: Sub-retinal fluid, No (n= 63, 129)
    58
    108
        Month 2: Sub-retinal fluid, Yes (n= 63, 129)
    2
    17
        Month 2: Sub-retinal fluid, NE (n= 63, 129)
    3
    4
        Month 2: Sub-retinal fluid, Missing (n= 63, 129)
    0
    0
        Month 6: Sub-retinal fluid, No (n= 60, 126)
    58
    109
        Month 6: Sub-retinal fluid, Yes (n= 60, 126)
    0
    14
        Month 6: Sub-retinal fluid, NE(n= 60, 126)
    2
    3
        Month 12: Sub-retinal fluid, No (n= 61, 124)
    60
    113
        Month 12: Sub-retinal fluid, Yes (n= 61, 124)
    0
    8
        Month 12: Sub-retinal fluid, NE (n= 61, 124)
    1
    3
    No statistical analyses for this end point

    Primary: Number of patients treated and re-treated based on presence/absence of Clinically significant abnormalities

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on presence/absence of Clinically significant abnormalities
    End point description
    Presence of clinically significant abnormalities was assessed at baseline, month 1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of clinically significant abnormalities (Yes/No). For retreated patients, the presence/absence of clinically significant abnormalities was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients undergoing ocular examination during that time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Baseline: Clinically Significant Abnormal, No
    61
    103
        Baseline: Clinically Significant Abnormal, Yes
    9
    27
        Baseline: Clinically Significant Abnormal, Missing
    0
    0
        Month 1: Clinically Significant Abnorma, No
    60
    106
        Month 1: Clinically Significant Abnormal, Yes
    6
    24
        Month 1: Clinically Significant Abnormal, Missing
    4
    0
        Month 2: Clinically Significant Abnormal, No
    60
    103
        Month 2: Clinically Significant Abnormal, Yes
    5
    26
        Month 2:Clinically Significant Abnormal, Missing
    5
    1
        Month 3: Clinically Significant Abnormal, No
    56
    108
        Month 3: Clinically Significant Abnormal, Yes
    7
    20
        Month 3: Clinically Significant Abnormal, Missing
    7
    2
        Month 6: Clinically Significant Abnormal, No
    59
    110
        Month 6: Clinically Significant Abnormal, Yes
    3
    18
        Month 6: Clinically Significant Abnormal, Missing
    8
    2
        Month 12: Clinically Significant Abnormal, No
    61
    116
        Month 12: Clinically Significant Abnormal, Yes
    2
    12
        Month 12: Clinically Significant Abnormal, Missing
    7
    2
    Statistical analysis title
    		 Clinically significant abnormalities
    Statistical analysis description
    Presence vs. absence of clinically significant abnormalities
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0103
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.58
         upper limit
    		 30.23

    Primary: Number of patients treated and re-treated based on improvement in best corrective visual acuity (BCVA) < 5 letters

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on improvement in best corrective visual acuity (BCVA) < 5 letters
    End point description
    Improvement in BCVA < 5 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA < 5 letters (Yes/No) which was reported as Gain >= 5 letters versus Gain < 5 letters. For retreated patients, Gain >= 5 letters and Gain < 5 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients with improvement in BCVA < 5 letters from baseline to that time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month1, Month 2, Month 3, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Month 1: Gain >= 5 letters (n= 51, 97)
    37
    69
        Month 1: Gain < 5 letters (n= 51, 97)
    14
    28
        Month 2: Gain >= 5 letters (n= 50, 95)
    38
    70
        Month 2: Gain < 5 letters (n= 50, 95)
    12
    25
        Month 3: Gain >= 5 letters (n= 52, 94)
    37
    74
        Month 3: Gain < 5 letters (n= 52, 94)
    15
    20
        Month 6: Gain >= 5 letters (n= 48, 92)
    40
    70
        Month 6: Gain < 5 letters (n= 48, 92)
    8
    22
        Month 12: Gain >= 5 letters (n= 51, 92)
    43
    69
        Month 12: Gain < 5 letters (n= 51, 92)
    8
    23
    Statistical analysis title
    		 Gain < 5 letters vs. Gain >= 5 letters
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0854
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 5.33

    Primary: Number of patients treated and re-treated based on improvement in best corrective visual acuity (BCVA) < 10 letters

    		 Close Top of page
    End point title
    		 Number of patients treated and re-treated based on improvement in best corrective visual acuity (BCVA) < 10 letters
    End point description
    Improvement in BCVA < 10 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA < 10 letters (Yes/No) which was reported as Gain >= 10 letters versus Gain < 10 letters. For retreated patients, Gain >= 10 letters and Gain < 10 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. 'n' represents number of patients with improvement in BCVA < 10 letters from baseline to that time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month1, Month 2, Month 3, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Month 1: Gain >= 10 letters (n= 51, 97)
    13
    27
        Month 1: Gain < 10 letters (n= 51, 97)
    38
    70
        Month 2: Gain >= 10 letters (n= 50, 95)
    20
    40
        Month 2: Gain < 10 letters (n= 50, 95)
    30
    55
        Month 3: Gain >= 10 letters (n= 52, 94)
    22
    41
        Month 3: Gain < 10 letters (n= 52, 94)
    30
    53
        Month 6: Gain >= 10 letters (n= 48, 92)
    29
    50
        Month 6: Gain < 10 letters (n= 48, 92)
    19
    42
        Month 12: Gain >= 10 letters (n= 51, 92)
    28
    48
        Month 12: Gain < 10 letters (n= 51, 92)
    23
    44
    Statistical analysis title
    		 Gain < 10 letters vs. Gain >= 10 letters
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0114
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.23
         upper limit
    		 5.17

    Primary: Number of patients in different categories of changes from baseline in BCVA

    		 Close Top of page
    End point title
    		 Number of patients in different categories of changes from baseline in BCVA
    End point description
    Changes from baseline in BCVA are described for the ETDRS parameter considering the following categories at each assessment: “no change” if the change was equal to 0 letter, “worsening” if change < 0 letter , "improvement" if change > 0 letter. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change from baseline in BCVA (improved/worsened/stable) which was reported as Improved versus no change and worsened versus no change. For retreated patients, this variable was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value, the value was considered as missing for this analysis. 'n' represents number of patients in FAS set with evaluable BCVA at baseline and that time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month1, Month 2, Month 3, Month 6, Month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: Patients
        Month 1: No change (n= 66, 130)
    7
    18
        Month 1: Worsening (n= 66, 130)
    8
    15
        Month 1: Improvement (n= 66, 130)
    51
    97
        Month 2: No change (n= 65, 129)
    6
    9
        Month 2: Worsening (n= 65, 129)
    9
    25
        Month 2: Improvement (n= 65, 129)
    50
    95
        Month 3: No change (n= 63, 128)
    3
    9
        Month 3: Worsening (n= 63, 128)
    8
    25
        Month 3: Improvement (n= 63, 128)
    52
    94
        Month 6: No change (n= 62, 128)
    5
    6
        Month 6: Worsening (n= 62, 128)
    9
    30
        Month 6: Improvement (n= 62, 128)
    48
    92
        Month 12: No change (n= 63, 128)
    3
    7
        Month 12: Worsening (n= 63, 128)
    9
    29
        Month 12: Improvement (n= 63, 128)
    51
    92
    Statistical analysis title
    		 Change from BL in BCVA: Improved vs. No change
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0049
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 0.91
    Statistical analysis title
    		 Change from BL in BCVA: Worsened vs. No change
    Comparison groups
    Ranibizumab: Treated Once v Ranibizumab: Re-treated Once
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0461
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 44.52

    Secondary: Mean change in Best Corrected Visual Acuity (BCVA) from baseline to Month 6 and month 12 on study eye

    		 Close Top of page
    End point title
    		 Mean change in Best Corrected Visual Acuity (BCVA) from baseline to Month 6 and month 12 on study eye
    End point description
    Change from baseline in BCVA (Best Corrected Visual Acuity) was Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. Patients with a BCVA ETDRS letter score of 78 to 24 in the study eye were included; A higher score represents better functioning of the study eye. A positive change from baseline shows improvement. Full Analysis Set (FAS): all patients who received at least one dose of ranibizumab. The study eyes of the patients belong to FAS were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, month 6, month 12
    End point values
    		 Ranibizumab
    Number of subjects analysed
    200
    Units: letters
    arithmetic mean (standard deviation)
        Change at 6 month (n=190)
    7.51 ( 11.68 )
        Change at 12 month (n=191)
    8.42 ( 12.81 )
    No statistical analyses for this end point

    Secondary: Mean number of ranibizumab injection

    		 Close Top of page
    End point title
    		 Mean number of ranibizumab injection
    End point description
    Mean number of ranibizumab injection is reported as number of injections per patient. Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab
    End point type
    Secondary
    End point timeframe
    baseline to month 12
    End point values
    		 Ranibizumab
    Number of subjects analysed
    200
    Units: number of injections
        arithmetic mean (standard deviation)
    2.41 ( 1.53 )
    No statistical analyses for this end point

    Secondary: Time to re-treatment

    		 Close Top of page
    End point title
    		 Time to re-treatment
    End point description
    Time to re-treatment, defined as time in months from the data of first dose of ranibizumab to the date of re-treatment, was evaluated. Full Analysis Set (FAS): all subjects who received at least one dose of ranibizumab
    End point type
    Secondary
    End point timeframe
    Baseline to Month 12
    End point values
    		 Ranibizumab: Re-treated Once
    Number of subjects analysed
    130
    Units: Months
        arithmetic mean (standard deviation)
    2.56 ( 2.17 )
    No statistical analyses for this end point

    Secondary: Number of patients having ocular and/or systemic adverse event (AE)

    		 Close Top of page
    End point title
    		 Number of patients having ocular and/or systemic adverse event (AE)
    End point description
    Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported. Safety Population: all subjects who received at least one dose of ranibizumab and had at least one post-baseline safety assessment
    End point type
    Secondary
    End point timeframe
    baseline to month 12
    End point values
    		 Ranibizumab
    Number of subjects analysed
    200
    Units: Patients
        Any systemic Adverse Event
    30
        Serious systemic Adverse Event
    5
        Ocular Adverse Event
    41
        Ocular serious adverse event
    2
    No statistical analyses for this end point

    Secondary: Change in patient quality of life from baseline to month 2 and month 12

    		 Close Top of page
    End point title
    		 Change in patient quality of life from baseline to month 2 and month 12
    End point description
    Patient quality of life was assessed by Impact of Vision Impairment (IVI) questionnaire. IVI is a 32-item instrument, either self- or interviewer-administered, developed to measure the impact of vision impairment on daily activities in five domains. The 32 items were divided into 5 domains as follows: Leisure and work (items 1 to 5), Social and consumer interaction (items 6 to 10 and items 23-24), Household and personal care (items 11 to 14 and items 20-21), Mobility (items 15 to 19 and item 22), Emotional reaction to vision loss (items 25 to 32). Responses to the IVI items were rated on a five-category Likert scale: not at all, 0; hardly at all, 1; a little, 2; a fair amount, 3; a lot, 4; and can’t do because of eyesight, 5. Total score was an arithmetic average of the items rated between 0 (the best score) and 5 (the worst score). A negative change indicates improvement. Data was computed on items with non missing response.
    End point type
    Secondary
    End point timeframe
    Baseline, month 2, month 12
    End point values
    		 Ranibizumab: Treated Once Ranibizumab: Re-treated Once
    Number of subjects analysed
    70
    130
    Units: units on a scale
    arithmetic mean (standard deviation)
        Change at Month 2 (n= 60, 124)
    -0.4 ( 0.68 )
    -0.15 ( 0.6 )
        Change at month 12 (n= 59, 122)
    -0.54 ( 0.91 )
    -0.36 ( 0.81 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.(up to 12 months)
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Ranibizumab
    Reporting group description
    		 Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection. Further injections might be required when monitoring reveals disease activity.

    Serious adverse events
    		 Ranibizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 200 (3.50%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Expired product administered (Study Eye)
         subjects affected / exposed
    2 / 200 (1.00%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Atrioventricular block
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Klebsiella sepsis
         subjects affected / exposed
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Ranibizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    26 / 200 (13.00%)
    Eye disorders
    Choroidal neovascularisation (Non-study Eye)
         subjects affected / exposed
    3 / 200 (1.50%)
         occurrences all number
    3
    Choroidal neovascularisation (Study Eye)
         subjects affected / exposed
    7 / 200 (3.50%)
         occurrences all number
    9
    Conjunctival haemorrhage (Study Eye)
         subjects affected / exposed
    4 / 200 (2.00%)
         occurrences all number
    4
    Conjunctival hyperaemia (Both Eyes)
         subjects affected / exposed
    5 / 200 (2.50%)
         occurrences all number
    6
    Ocular hypertension (Both Eyes)
         subjects affected / exposed
    4 / 200 (2.00%)
         occurrences all number
    4
    Infections and infestations
    Influenza
         subjects affected / exposed
    7 / 200 (3.50%)
         occurrences all number
    7

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Mar 2014
    - The amendment made some laboratory evaluations (high sensivity C-reactive protein - hsCRP, serum amyloid associated protein - SAA, C3 and C4, S100, fibrinogen) optional due to the difficulties in performing these assessments at several sites. - Minor revisions were made with regard to inclusion criteria (eligibility in bilateral mCNV patients), exclusion criteria (definition of pregnancy), concomitant medications and reference therapy.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 07 02:00:37 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA