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Safety and Efficacy of Ranibizumab in Japanese Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration

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ClinicalTrials.gov Identifier: NCT00284089
Recruitment Status : Completed
First Posted : January 31, 2006
Results First Posted : February 11, 2011
Last Update Posted : February 24, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Subfoveal Choroidal Neovascularization(CNV) Secondary to Age-related Macular Degeneration (AMD)
Intervention Drug: Ranibizumab
Enrollment 88
Recruitment Details  
Pre-assignment Details In total, 88 patients were enrolled in the study, 12 in Group A and 76 in Group B. The single dose phase of the study (Group A patients only) was completed prior to initiation of the multiple dose phase (Groups A and B).
Arm/Group Title Group A: Ranibizumab 0.3 mg Group A: Ranibizumab 0.5 mg Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years. In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years. Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years. Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
Period Title: Single Dose Phase
Started 6 6 0 [1] 0 [1]
Completed 6 6 0 0
Not Completed 0 0 0 0
[1]
Group B patients did not participate in the Single Dose Phase of the study.
Period Title: Multiple Dose Phase
Started 5 [1] 6 35 41
Completed 4 6 31 37
Not Completed 1 0 4 4
Reason Not Completed
Adverse Event             1             0             1             1
Protocol Violation             0             0             1             0
Withdrawal by Subject             0             0             1             2
Death             0             0             1             1
[1]
1 subject chose to receive other treatment & discontinued before starting the multiple dose phase.
Period Title: Extension Phase
Started 3 [1] 6 [1] 28 [1] 33 [1]
Completed 1 6 22 21
Not Completed 2 0 6 12
Reason Not Completed
Adverse Event             0             0             2             2
condition no longer requires study drug             2             0             2             7
Protocol Violation             0             0             1             0
Withdrawal by Subject             0             0             1             3
[1]
Patients providing written consent & satisfying eligibility criteria could enter the extension phase
Arm/Group Title Group A: Ranibizumab 0.3 mg Group A: Ranibizumab 0.5 mg Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg Total
Hide Arm/Group Description In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years. In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years. Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years. Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years. Total of all reporting groups
Overall Number of Baseline Participants 6 6 35 41 88
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 35 participants 41 participants 88 participants
50 to <65 years 2 0 8 10 20
65 to <75 years 2 4 16 13 35
75 to <85 years 2 2 10 15 29
>= 85 years 0 0 1 3 4
[1]
Measure Description: Age demographics for those subjects enrolled in the single and multiple dose phases of the study.
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 35 participants 41 participants 88 participants
50 to <65 years 1 0 7 10 18
65 to <75 years 1 4 14 10 29
75 to <85 years 1 2 6 12 21
>= 85 years 0 0 1 1 2
[1]
Measure Description: Age demographics for those subjects enrolled in the extension phase of the study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 35 participants 41 participants 88 participants
Female
1
  16.7%
1
  16.7%
9
  25.7%
8
  19.5%
19
  21.6%
Male
5
  83.3%
5
  83.3%
26
  74.3%
33
  80.5%
69
  78.4%
[1]
Measure Description: Gender demographics for those subjects enrolled in the single and multiple dose phases of the study.
Gender   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 35 participants 41 participants 88 participants
Female 0 1 9 5 15
Male 3 5 19 28 55
[1]
Measure Description: Gender demographics for those subjects enrolled in the extension phase of the study.
1.Primary Outcome
Title Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
Hide Description The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. The Last Observation Carried Forward (LOCF) was used to impute missing data at month 6 in the ITT analysis.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 35 41
Mean (Standard Deviation)
Unit of Measure: Number of Letters
Baseline 47.6  (11.82) 48.1  (10.75)
Month 6 55.7  (13.16) 57.1  (14.99)
Change from Baseline 8.1  (12.65) 9.0  (9.62)
2.Secondary Outcome
Title Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
Hide Description The efficacy assessment was based on Group B patients. BCVA was assessed during all study visits using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the efficacy variable. The Last Observation carried Forward (LOCF) was used to impute missing data at month 12 in the ITT analysis.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 35 41
Mean (Standard Deviation)
Unit of Measure: Number of Letters
Baseline 47.6  (11.82) 48.1  (10.75)
Month 12 57.1  (12.91) 58.6  (15.44)
Change from Baseline 9.5  (12.79) 10.5  (11.14)
3.Secondary Outcome
Title Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Hide Description BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, using LOCF.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 35 41
Measure Type: Number
Unit of Measure: Participants
Loss of < 15 letters from Baseline at month 6 34 41
Loss of < 15 letters from Baseline at month 12 34 41
Gain of ≥15 letters from Baseline at month 6 12 10
Gain of ≥15 letters from Baseline at month 12 13 13
Loss of ≥30 letters from Baseline at month 6 0 0
Loss of ≥30 letters from Baseline at month 12 0 0
Visual acuity < 34 letters at Month 6 2 2
Visual acuity < 34 letters at Month 12 2 1
4.Secondary Outcome
Title Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Hide Description Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time Frame Month 12 (start of extension phase) and last visit of extension phase. Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all enrolled patients in the extension phase. For the analysis of the results of the extension phase, all data are presented as observed. Patients must have values both at Month 12 and Last Visit to be included.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
Overall Number of Participants Analyzed 28 33
Mean (Standard Deviation)
Unit of Measure: Letters
Baseline 47.9  (12.59) 50.0  (10.38)
Month 12 59.1  (11.69) 59.8  (15.07)
Last visit 55.4  (17.14) 57.6  (15.36)
Change from Month 12 -3.6  (14.82) -2.2  (7.92)
5.Secondary Outcome
Title Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
Hide Description

BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The following categories were evaluated:

  • Participants with a BCVA score loss of fewer than 15 letters from baseline at Last Visit
  • Participants with a BCVA score loss of 30 or more letters from baseline at Last Visit
  • Participants with a BCVA score gain of 15 or more letters from baseline at Last Visit
  • Participants with a BCVA score of less than 34 letters at Last Visit
Time Frame Baseline and last visit of extension phase - Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
Hide Outcome Measure Data
Hide Analysis Population Description
Includes patients enrolled in the extension phase, observed data.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
Overall Number of Participants Analyzed 28 33
Measure Type: Number
Unit of Measure: Participants
Loss of < 15 letters from Baseline 24 32
Gain of ≥15 letters from Baseline 9 9
Loss of ≥30 letters from Baseline 1 1
Visual acuity < 34 letters 3 1
6.Secondary Outcome
Title Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Hide Description Choroidal Neovascularization was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The area of Choroidal Neovascularization is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm^2 on the retina).
Time Frame Baseline, Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 35 41
Mean (Standard Deviation)
Unit of Measure: disc areas
Baseline [N=35, 41] 2.11  (1.10) 2.03  (1.66)
Mean change from Baseline at Month 3 [N=34, 40] -0.10  (0.95) 0.13  (0.75)
Mean change from Baseline at Month 6 [N=34, 40] -0.15  (0.97) 0.04  (0.76)
Mean change from Baseline at Month 9 [N=34, 40] -0.23  (0.97) 0.21  (0.90)
Mean change from Baseline at Month 12 [N=34, 40] -0.16  (1.01) 0.23  (1.08)
7.Secondary Outcome
Title Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Hide Description Area of leakage from CNV plus staining of retinal pigment epithelium was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The total area is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm^2 on the retina).
Time Frame Baseline, Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 35 41
Mean (Standard Deviation)
Unit of Measure: disc areas
Baseline [N=35, 41] 2.31  (1.17) 2.49  (1.54)
Mean change from Baseline at Month 3 [N=34, 40] -0.76  (0.85) -0.74  (1.21)
Mean change from Baseline at Month 6 [N=34, 40] -1.21  (0.87) -1.10  (1.19)
Mean change from Baseline at Month 9 [N=34, 40] -1.39  (1.02) -1.26  (1.45)
Mean change from Baseline at Month 12 [N=34, 40] -1.50  (1.08) -1.39  (1.48)
8.Secondary Outcome
Title Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Hide Description Area of leakage was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed at the central reading center.
Time Frame Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and for whom data was available. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 34 40
Measure Type: Number
Unit of Measure: Percentage of participants
Month 3 2.9 7.5
Month 6 8.8 15.0
Month 9 26.5 25.0
Month 12 35.3 35.0
9.Secondary Outcome
Title Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Hide Description Foveal retinal thickness was assessed by Optical Coherence Tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Time Frame Baseline, Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes Group B Intent-to treat (ITT) population, observed data. OCT was performed in a total of 58 patients at selected sites.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 28 30
Mean (Standard Deviation)
Unit of Measure: micrometers
Baseline [N=28, 30] 336.7  (195.3) 370.7  (171.9)
Mean change from Baseline at Month 3 [N=27, 29] -124.4  (141.6) -195.6  (187.5)
Mean change from Baseline at Month 6 [N=26, 28] -142.9  (199.3) -225.6  (192.2)
Mean change from Baseline at Month 9 [N=26, 27] -188.4  (190.1) -245.4  (203.1)
Mean change from Baseline at Month 12 [N=26, 26] -194.0  (199.8) -257.8  (209.8)
10.Secondary Outcome
Title Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Hide Description Total retinal volume was assessed by Optical Coherence tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Time Frame Baseline, Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
OCT was performed in a total of 58 patients at selected sites. Group B Intent-to treat (ITT) population, observed data only are included. The assessed sample size was small for total retinal volume data because the central reading center judged "Can not grade" due to retinal pigment epithelium disruption associated with CNV secondary to AMD.
Arm/Group Title Group B: Ranibizumab 0.3 mg Group B: Ranibizumab 0.5 mg
Hide Arm/Group Description:
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
Overall Number of Participants Analyzed 28 30
Mean (Standard Deviation)
Unit of Measure: micrometers
Baseline [N=11, 11] 7.23  (0.84) 7.36  (0.97)
Mean change from Baseline at Month 3 [N=7, 7] -0.78  (0.74) -0.67  (0.71)
Mean change from Baseline at Month 6 [N=6, 6] -0.52  (0.60) -0.92  (0.96)
Mean change from Baseline at Month 9 [N=4, 5] -0.48  (0.03) -0.28  (0.83)
Mean change from Baseline at Month 12 [N=6, 6] -0.95  (1.14) -0.42  (0.67)
Time Frame The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Core Group A+B: Ranibizumab 0.3 mg Core Group A+B: Ranibizumab 0.5 mg Extension Group A+B: Ranibizumab 0.3 mg Extension Group A+B: Ranibizumab 0.5 mg
Hide Arm/Group Description "Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.3 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye. "Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.5 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye. In the extension phase, enrolled patients received an intravitreal injection of 0.3 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years. In the extension phase, all patients received an intravitreal injection of 0.5 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
All-Cause Mortality
Core Group A+B: Ranibizumab 0.3 mg Core Group A+B: Ranibizumab 0.5 mg Extension Group A+B: Ranibizumab 0.3 mg Extension Group A+B: Ranibizumab 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Core Group A+B: Ranibizumab 0.3 mg Core Group A+B: Ranibizumab 0.5 mg Extension Group A+B: Ranibizumab 0.3 mg Extension Group A+B: Ranibizumab 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/41 (12.20%)   8/47 (17.02%)   5/31 (16.13%)   8/39 (20.51%) 
Cardiac disorders         
Angina pectoris  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Eye disorders         
Cataract (Fellow eye)  1  1/41 (2.44%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Corneal oedema (Study eye)  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Eye pain (Study eye)  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Glaucomatocyclitic crises (Study eye)  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Macular degeneration (Fellow eye)  1  1/41 (2.44%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Macular degeneration (Study eye)  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Retinal detachment (Study eye)  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Visual acuity reduced (Fellow eye)  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Visual acuity reduced (Study eye)  1  1/41 (2.44%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Visual acuity reduced transiently (Study eye)  1  0/41 (0.00%)  2/47 (4.26%)  0/31 (0.00%)  0/39 (0.00%) 
Vitreous haemorrhage (Study eye)  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Gastrointestinal disorders         
Colonic polyp  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Enterocele  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Gastric polyps  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Infections and infestations         
Abscess neck  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Injury, poisoning and procedural complications         
Overdose (Study eye)  1  0/41 (0.00%)  2/47 (4.26%)  0/31 (0.00%)  0/39 (0.00%) 
Investigations         
Intraocular pressure increased (Study eye)  1  0/41 (0.00%)  2/47 (4.26%)  0/31 (0.00%)  0/39 (0.00%) 
Metabolism and nutrition disorders         
Anorexia  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Diabetes mellitus  1  1/41 (2.44%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Bladder neoplasm  1  1/41 (2.44%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Colon cancer  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  0/39 (0.00%) 
Gastric cancer  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  1/39 (2.56%) 
Lung carcinoma cell type unspecified recurrent  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Small cell lung cancer stage unspecified  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Nervous system disorders         
Ataxia  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Cerebral haemorrhage  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Cerebral infarction  1  0/41 (0.00%)  0/47 (0.00%)  1/31 (3.23%)  1/39 (2.56%) 
Hypoaesthesia  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Spondylitic myelopathy  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Psychiatric disorders         
Depression  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Respiratory, thoracic and mediastinal disorders         
Emphysema  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Core Group A+B: Ranibizumab 0.3 mg Core Group A+B: Ranibizumab 0.5 mg Extension Group A+B: Ranibizumab 0.3 mg Extension Group A+B: Ranibizumab 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/41 (92.68%)   43/47 (91.49%)   27/31 (87.10%)   28/39 (71.79%) 
Eye disorders         
Conjunctival haemorrhage (Study eye)  1  30/41 (73.17%)  28/47 (59.57%)  13/31 (41.94%)  14/39 (35.90%) 
Conjunctival hyperaemia (Study eye)  1  8/41 (19.51%)  8/47 (17.02%)  2/31 (6.45%)  1/39 (2.56%) 
Conjunctivitis allergic (Fellow eye)  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  2/39 (5.13%) 
Conjunctivitis allergic (Study eye)  1  1/41 (2.44%)  1/47 (2.13%)  0/31 (0.00%)  2/39 (5.13%) 
Eye pain (Study eye)  1  9/41 (21.95%)  10/47 (21.28%)  2/31 (6.45%)  0/39 (0.00%) 
Myodesopsia (Study eye)  1  0/41 (0.00%)  0/47 (0.00%)  0/31 (0.00%)  3/39 (7.69%) 
Ocular hyperaemia (Study eye)  1  0/41 (0.00%)  3/47 (6.38%)  0/31 (0.00%)  0/39 (0.00%) 
Polypoidal choroidal vasculopathy (Fellow eye)  1  0/41 (0.00%)  0/47 (0.00%)  2/31 (6.45%)  0/39 (0.00%) 
Punctate keratitis (Study eye)  1  7/41 (17.07%)  4/47 (8.51%)  1/31 (3.23%)  1/39 (2.56%) 
Retinal detachment (Study eye)  1  5/41 (12.20%)  2/47 (4.26%)  2/31 (6.45%)  5/39 (12.82%) 
Retinal haemorrhage (Fellow eye)  1  3/41 (7.32%)  5/47 (10.64%)  6/31 (19.35%)  2/39 (5.13%) 
Retinal haemorrhage (Study eye)  1  12/41 (29.27%)  5/47 (10.64%)  9/31 (29.03%)  10/39 (25.64%) 
Visual acuity reduced (Study eye)  1  1/41 (2.44%)  3/47 (6.38%)  1/31 (3.23%)  0/39 (0.00%) 
Vitreous detachment (Study eye)  1  3/41 (7.32%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Vitreous floaters (Study eye)  1  1/41 (2.44%)  3/47 (6.38%)  0/31 (0.00%)  0/39 (0.00%) 
Gastrointestinal disorders         
Constipation  1  4/41 (9.76%)  1/47 (2.13%)  1/31 (3.23%)  1/39 (2.56%) 
Dental caries  1  2/41 (4.88%)  1/47 (2.13%)  1/31 (3.23%)  2/39 (5.13%) 
Diarrhoea  1  2/41 (4.88%)  3/47 (6.38%)  1/31 (3.23%)  0/39 (0.00%) 
Nausea  1  3/41 (7.32%)  1/47 (2.13%)  0/31 (0.00%)  0/39 (0.00%) 
Infections and infestations         
Gastroenteritis  1  0/41 (0.00%)  0/47 (0.00%)  2/31 (6.45%)  0/39 (0.00%) 
Nasopharyngitis  1  7/41 (17.07%)  10/47 (21.28%)  6/31 (19.35%)  9/39 (23.08%) 
Injury, poisoning and procedural complications         
Fall  1  0/41 (0.00%)  1/47 (2.13%)  1/31 (3.23%)  2/39 (5.13%) 
Investigations         
Intraocular pressure increased (Study eye)  1  2/41 (4.88%)  6/47 (12.77%)  2/31 (6.45%)  4/39 (10.26%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  0/41 (0.00%)  2/47 (4.26%)  3/31 (9.68%)  0/39 (0.00%) 
Nervous system disorders         
Headache  1  4/41 (9.76%)  1/47 (2.13%)  2/31 (6.45%)  1/39 (2.56%) 
Reproductive system and breast disorders         
Prostatomegaly  1  3/41 (7.32%)  0/47 (0.00%)  0/31 (0.00%)  0/39 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/41 (0.00%)  1/47 (2.13%)  0/31 (0.00%)  2/39 (5.13%) 
Skin and subcutaneous tissue disorders         
Eczema  1  3/41 (7.32%)  3/47 (6.38%)  0/31 (0.00%)  0/39 (0.00%) 
Vascular disorders         
Hypertension  1  3/41 (7.32%)  1/47 (2.13%)  4/31 (12.90%)  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Layout table for additonal information
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00284089    
Other Study ID Numbers: CRFB002A1201
First Submitted: January 30, 2006
First Posted: January 31, 2006
Results First Submitted: January 20, 2011
Results First Posted: February 11, 2011
Last Update Posted: February 24, 2011