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Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD (TREND)

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ClinicalTrials.gov Identifier: NCT01948830
Recruitment Status : Completed
First Posted : September 24, 2013
Results First Posted : December 15, 2016
Last Update Posted : April 17, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Supportive Care
Conditions Age-related Macular Degeneration
Choroidal Neovascularization
Intervention Drug: Ranibizumab 0.5mg
Enrollment 650
Recruitment Details  
Pre-assignment Details

Patients were randomized 1:1 into one of two treatment arms, Treat and Extend or monthly regimens.

Safety set: One patient was randomized but did not receive at least one study treatment and did not record at least one post-baseline safety assessment

Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Period Title: Overall Study
Started 323 327
Safety Set 323 326
Completed 290 295
Not Completed 33 32
Reason Not Completed
Physician Decision             1             3
Protocol deviation             1             2
Lost to Follow-up             5             4
Withdrawal by Subject             14             17
Adverse Event             9             2
Death             3             4
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly Total
Hide Arm/Group Description Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen Ranibizumab 0.5 mg/0.05 mL (Monthly regimen) Total of all reporting groups
Overall Number of Baseline Participants 323 327 650
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 323 participants 327 participants 650 participants
75.3  (8.61) 75.2  (8.13) 75.2  (8.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 327 participants 650 participants
Female
179
  55.4%
181
  55.4%
360
  55.4%
Male
144
  44.6%
146
  44.6%
290
  44.6%
1.Primary Outcome
Title Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12
Hide Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement
Time Frame Baseline to month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and study completion after last observational carried forward (LOCF) were included in this analysis. LOCF was used as an imputation of missing data.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 320 323
Least Squares Mean (Standard Error)
Unit of Measure: Letters (EDTRS)
6.2  (0.70) 8.1  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group I Ranibizumab 0.5 mg TER, Group II Ranibizumab 0.5 mg Monthly
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The following hypothesis was tested at a one-sided 0.025 level. Non-inferiority with respect to BCVA: H01: μtreat and extend - μmonthly ≤ - Δ versus HA1: μtreat and extend - μmonthly > - Δ where μtreat and extend and μmonthly are the unknown mean changes from baseline in BCVA to Month 12 in the treat and extend regimen and the monthly regimen, respectively. Δ is the non-inferiority margin and is pre-defined to be 5 letters for the justification of the margin.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Number of Visits Scheduled
Hide Description The number of visits scheduled according to the treat and extend regimen after treatment initiation
Time Frame From Month1 to Month 11
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was analyzed.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Mean (Standard Deviation)
Unit of Measure: Number of visits
8.9  (2.56) 11.2  (2.37)
3.Secondary Outcome
Title Change in BCVA From Baseline to Month 12
Hide Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and study completion after last observational carried forward (LOCF) were included in this analysis. LOCF was used as an imputation of missing data.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 320 323
Mean (Standard Deviation)
Unit of Measure: Letters (EDTRS)
6.4  (14.11) 8.0  (11.61)
4.Secondary Outcome
Title Average BCVA Change From Baseline to Month 12
Hide 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 Baseline to Month 12

Time Frame Baseline and every month for 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and average visual acuity (VA) from month 1 to study completion were included in this analysis.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 320 323
Mean (Standard Deviation)
Unit of Measure: Letters (EDTRS)
6.3  (10.50) 7.1  (9.41)
5.Secondary Outcome
Title Mean Change in Visual Acuity BCVA (Letters) From Baseline to Month 12
Hide Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and compare to Baseline
Time Frame Baseline and every month for 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and the specific post-baseline visit.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Mean (Standard Deviation)
Unit of Measure: Letters (EDTRS)
Month 1 (n=320, 322) 4.6  (7.56) 4.2  (6.98)
Month 2 (n=240, 316) 5.5  (8.64) 5.8  (8.58)
Month 3 (n=247, 311) 6.7  (9.09) 6.7  (9.19)
Month 4 (n=213, 314) 7.0  (10.90) 7.3  (9.95)
Month 5 (n=231, 302) 6.0  (11.34) 7.7  (10.61)
month 6 (n=205, 302) 6.9  (13.34) 7.9  (10.83)
Month 7 (n=230, 298) 5.9  (14.25) 7.9  (11.36)
Month 8 (n=210, 295) 7.5  (12.87) 7.9  (11.34)
Month 9 (n=179, 295) 6.6  (13.63) 7.6  (12.56)
Month 10 (n=202, 296) 6.3  (13.44) 7.6  (12.06)
Month 11 (n=180, 290) 5.9  (14.12) 7.5  (12.48)
Month 12 (n=294, 295) 6.6  (13.41) 7.9  (11.96)
6.Secondary Outcome
Title Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12
Hide Description BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 12 as compared with baseline
Time Frame Baseline and every month for 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and the specific post-baseline visit were included for this analysis.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Measure Type: Number
Unit of Measure: Number of participants
Month 1,Gain of ≥ 1 letter (n=320,322) 235 233
Month 1, Gain of ≥ 5 letters 145 145
Month 1, Gain of ≥ 10 letters 65 58
Month 1, Gain of ≥ 15 letters 24 23
Month 1, Gain of ≥ 30 letters 4 2
Month 2, Gain of >= 1 letter (n=226, 316) 168 244
Month 2, Gain of >= 5 letters 123 184
Month 2, Gain of >= 10 letters 60 88
Month 2, Gain of >= 15 letters 30 39
Month 2, Gain of >= 30 letters 4 3
Month 3, Gain of >= 1 letter (n=161,311) 120 244
Month 3, Gain of >= 5 letters 98 187
Month 3, Gain of >= 10 letters 57 110
Month 3, Gain of >= 15 letters 28 46
Month 3, Gain of >= 30 letters 2 3
Month 4, Gain of >= 1 letter (n=128, 314) 96 249
Month 4, Gain of >= 5 letters 67 198
Month 4, Gain of >=10 letters 48 118
Month 4, Gain of >= 15 letters 25 60
Month 4, Gain of >= 30 letters 4 8
Month 5, Gain of >= 1 letter (n=114, 302) 84 243
Month 5, Gain of >= 5 letters 64 197
Month 5, Gain of >= 10 letters 42 116
Month 5, Gain of >= 15 letters 19 59
Month 5, Gain of >= 30 letters 3 10
Month 6, Gain of >= 1 letter (n=117, 302) 85 238
Month 6, Gain of >= 5 letters 68 197
Month 6, Gain of >= 10 letters 42 125
Month 6, Gain of >= 15 letters 19 61
Month 6, Gain of >= 30 letters 2 11
Month 7, Gain of >= 1 letter (n=176, 298) 126 235
Month 7, Gain of >= 5 letters 94 196
Month 7, Gain of >= 10 letters 57 123
Month 7, Gain of >= 15 letters 33 69
Month 7, Gain of >= 30 letters 7 9
Month 8, Gain of >= 1 letter (n=163, 295) 124 228
Month 8, Gain of >= 5 letters 108 198
Month 8, Gain of >= 10 letters 69 130
Month 8, Gain of >= 15 letters 40 72
Month 8, Gain of >= 30 letters 4 9
Month 9, Gain of >= 1 letter (n=129, 295) 93 229
Month 9, Gain of >= 5 letters 78 186
Month 9, Gain of >= 10 letters 52 128
Month 9, Gain of >= 15 letters 28 70
Month 9, Gain of >= 30 letters 5 8
Month 10, Gain of >= 1 letter (n=159, 296) 113 230
Month 10, Gain of >= 5 letters 98 190
Month 10, Gain of >= 10 letters 60 126
Month 10, Gain of >= 15 letters 32 74
Month 10, Gain of >= 30 letters 4 10
Month 11, Gain of >= 1 letter (131, 290) 94 222
Month 11, Gain of >= 5 letters 79 187
Month 11, Gain of >= 10 letters 51 130
Month 11, Gain of >= 15 letters 32 74
Month 11, Gain of >= 30 letters 5 9
Month 12, Gain of >= 1 letter (n=291, 295) 217 226
Month 12, Gain of >= 5 letters 178 199
Month 12, Gain of >= 10 letters 123 135
Month 12, Gain of >= 15 letters 75 77
Month 12, Gain of >= 30 letters 12 8
7.Secondary Outcome
Title Number of Patients With Best Corrected Visual Acuity (BCVA) Loss <5, <10, and <15 Letters by Visit
Hide 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.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 and every month for 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and the specific post-baseline visit were included for this analysis.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Measure Type: Number
Unit of Measure: Number of participants
Month 1, Loss of < 5 letters (n=320, 322) 296 295
Month 1, Loss of < 10 letters 313 314
Month 1, Loss of < 15 letters 319 320
Month 2, Loss of < 5 letters (n=226, 316) 205 288
Month 2, Loss of < 10 letters 220 306
Month 2, Loss of < 15 letters 223 309
Month 3, Loss of < 5 letters (n=161, 311) 146 289
Month 3, Loss of < 10 letters 158 299
Month 3, Loss of < 15 letters 160 304
Month 4, Loss of < 5 letters (n=128, 314) 114 286
Month 4, Loss of < 10 letters 128 301
Month 4, Loss of < 15 letters 124 307
Month 5, Loss of < 5 letters (n=114, 302) 97 276
Month 5, Loss of < 10 letters 105 287
Month 5, Loss of < 15 letters 108 295
Month 6, Loss of < 5 letters (n=117, 302) 104 271
Month 6, Loss of < 10 letters 110 286
Month 6, Loss of < 15 letters 111 298
Month 7, Loss of < 5 letters (n=176, 298) 148 268
Month 7, Loss of < 10 letters 162 279
Month 7, Loss of < 15 letters 166 289
Month 8, Loss of < 5 letters (n=163, 295) 145 262
Month 8, Loss of < 10 letters 155 276
Month 8, Loss of < 15 letters 155 286
Month 9, Loss of < 5 letters (n=129, 295) 110 258
Month 9, Loss of < 10 letters 120 270
Month 9, Loss of < 15 letters 122 281
Month 10, Loss of < 5 letters(n=159, 296) 133 253
Month 10, Loss of < 10 letters 147 276
Month 10, Loss of < 15 letters 150 285
Month 11, Loss of < 5 letters (n=131, 290) 105 251
Month 11, Loss of < 10 letters 118 263
Month 11, Loss of < 15 letters 121 275
Month 12, Loss of < 5 letters (291, 295) 247 256
Month 12, Loss of < 10 letters 267 272
Month 12, Loss of < 15 letters 273 284
8.Secondary Outcome
Title Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12
Hide Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 12 indicates a positive outcome
Time Frame Baseline and every month for 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and the specific post-baseline visit were included for this analysis.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Measure Type: Number
Unit of Measure: Number of participants
Month 1 (n=320, 322) 106 106
Month 2 (n=226, 316) 74 136
Month 3 (n=161, 311) 67 148
Month 4 (n=128, 314) 60 147
Month 5 (n=114, 302) 51 156
Month 6 (n=117, 302) 58 155
Month 7 (n=176, 298) 78 150
Month 8 (n=163, 295) 84 155
Month 9 (n=129, 295) 68 156
Month 10 (n=159, 296) 74 149
Month 11 (n=131, 290 63 143
Month 12 (n=291, 295) 131 149
9.Secondary Outcome
Title The Mean Number of Treatment Frequency
Hide Description The number of injections received
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) comprised all patients to whom treatment regimen had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment regimen they were assigned to at randomization
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Mean (Standard Deviation)
Unit of Measure: Number of injections
8.7  (2.68) 11.0  (2.50)
10.Secondary Outcome
Title The Average Number of Days Between Injections
Hide Description The average dosing interval was measured as the average number of days between injections
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) comprised all patients to whom treatment regimen had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment regimen they were assigned to at randomization
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Mean (Standard Deviation)
Unit of Measure: days
40.3  (11.28) 29.4  (3.27)
11.Secondary Outcome
Title Percentage of Participants With Fluid Free Macula Over Time up to Month 12
Hide Description OCT (optical coherence tomography) was used to assess intra-retinal fluid as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography). Fluid free macula refers to absence of macular edema (as assessed by the reading center). The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the macular edema (center involvement) at study completion. These total counts are used as the denominator for the percentages
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) comprised all patients to whom treatment regimen had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment regimen they were assigned to at randomization
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 291 290
Measure Type: Number
Unit of Measure: Percentage of participants
Absent 60.5 60.7
Definite 39.5 39
Can't grade 0.0 0.3
12.Secondary Outcome
Title Change in Central Subfield Retinal Thickness (CSFT) Over Time
Hide 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. The Ns in the rows is the number of patients with a value for both baseline and the specific post-baseline visit
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and the specific post-baseline visit were included for this analysis.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 323 327
Mean (Standard Deviation)
Unit of Measure: microns
Month 1 (n=311, 316) -137.6  (132.33) -126.8  (119.47)
Month 2 (n=220, 311) -151.6  (151.15) -149.2  (137.60)
Month 3 (n=157, 304) -149.8  (167.26) -151.8  (149.51)
Month 4 (n=125, 307) -141.8  (183.71) -161.3  (149.36)
Month 5 (n=110, 295) -138.6  (160.04) -160.9  (148.23)
Month 6 (n=113, 298) -140.1  (156.25) -163.4  (157.18)
Month 7 (n=173, 296) -146.6  (160.72) -166.9  (161.49)
Month 8 (n=159, 290) -153.4  (151.93) -170.4  (156.68)
Month 9 (n=126, 286) -150.2  (153.82) -169.3  (156.50)
Month 10 (n=156, 291) -154.6  (162.77) -170.9  (153.90)
Month 11 (n=127, 285) -133.1  (170.47) -174.8  (163.16)
Month 12 (n=289, 287) -172.1  (162.81) -173.3  (154.13)
13.Secondary Outcome
Title Percentage of Patients With Choroidal Neovascularization (CNV) Leakage Assessed by Fluorescein Angiography (FA) in the Study Eye at
Hide Description To evaluate presence of active CNV leakage on fluorescein angiography (FA) by reading center over time up to Month 12. The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the presence of leakage at study completion. These total counts are used as the denominator for the percentages.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) comprised all patients to whom treatment regimen had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment regimen they were assigned to at randomization.
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 278 286
Measure Type: Number
Unit of Measure: Percentage of participants
Yes 18.7 17.1
No 74.1 76.9
Can't grade 0.0 2.4
Not applicable 7.2 3.5
14.Secondary Outcome
Title Change From Baseline in Composite Score of the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25)
Hide Description The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also ranged from 0 to 100 as they are calculated as total scores divided by the number of questions. The higher the values of total scores represent better outcome
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), comprised of all patients to whom treatment regimen had been assigned, was considered for the analysis. Only patients with the value for both Baseline and post-baseline value at the specific visit were included for this analysis
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description:
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
Overall Number of Participants Analyzed 290 293
Mean (Standard Deviation)
Unit of Measure: Score on a scale
2.3  (13.93) 4  (13.72)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Hide Arm/Group Description Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen Ranibizumab 0.5 mg/0.05 mL (Monthly regimen)
All-Cause Mortality
Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Affected / at Risk (%) Affected / at Risk (%)
Total   39/323 (12.07%)   42/326 (12.88%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  0/323 (0.00%)  1/326 (0.31%) 
Cardiac disorders     
Acute coronary syndrome  1  1/323 (0.31%)  0/326 (0.00%) 
Acute myocardial infarction  1  1/323 (0.31%)  0/326 (0.00%) 
Atrial fibrillation  1  1/323 (0.31%)  0/326 (0.00%) 
Atrioventricular block  1  0/323 (0.00%)  1/326 (0.31%) 
Cardiac failure  1  1/323 (0.31%)  1/326 (0.31%) 
Ischaemic cardiomyopathy  1  0/323 (0.00%)  1/326 (0.31%) 
Left ventricular dysfunction  1  0/323 (0.00%)  1/326 (0.31%) 
Myocardial infarction  1  2/323 (0.62%)  0/326 (0.00%) 
Palpitations  1  1/323 (0.31%)  0/326 (0.00%) 
Ventricular tachycardia  1  0/323 (0.00%)  1/326 (0.31%) 
Ear and labyrinth disorders     
Vertigo  1  2/323 (0.62%)  0/326 (0.00%) 
Vestibular disorder  1  0/323 (0.00%)  1/326 (0.31%) 
Endocrine disorders     
Hyperthyroidism  1  1/323 (0.31%)  0/326 (0.00%) 
Eye disorders     
Cataract (Fellow eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Corneal erosion (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Corneal infiltrates (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Dacryostenosis acquired (Fellow eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Dacryostenosis acquired (Study eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Macular hole (Study eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Retinal detachment (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Retinal haemorrhage (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Retinal tear (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Vitreous haemorrhage (Study eye)  1  1/323 (0.31%)  0/326 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/323 (0.00%)  1/326 (0.31%) 
Dyspepsia  1  0/323 (0.00%)  1/326 (0.31%) 
Intestinal obstruction  1  1/323 (0.31%)  0/326 (0.00%) 
Vomiting  1  1/323 (0.31%)  1/326 (0.31%) 
General disorders     
Non-cardiac chest pain  1  0/323 (0.00%)  1/326 (0.31%) 
Hepatobiliary disorders     
Bile duct stone  1  0/323 (0.00%)  1/326 (0.31%) 
Cholecystitis acute  1  1/323 (0.31%)  0/326 (0.00%) 
Cholecystitis chronic  1  0/323 (0.00%)  1/326 (0.31%) 
Hepatic cirrhosis  1  0/323 (0.00%)  1/326 (0.31%) 
Immune system disorders     
Drug hypersensitivity  1  0/323 (0.00%)  1/326 (0.31%) 
Infections and infestations     
Bronchitis  1  2/323 (0.62%)  0/326 (0.00%) 
Cellulitis  1  0/323 (0.00%)  1/326 (0.31%) 
Diverticulitis  1  1/323 (0.31%)  1/326 (0.31%) 
Endophthalmitis (Fellow eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Endophthalmitis (Study eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Erysipelas  1  0/323 (0.00%)  1/326 (0.31%) 
Infective exacerbation of chronic obstructive airways disease  1  0/323 (0.00%)  1/326 (0.31%) 
Paronychia  1  1/323 (0.31%)  0/326 (0.00%) 
Pneumonia  1  4/323 (1.24%)  2/326 (0.61%) 
Pneumonia mycoplasmal  1  1/323 (0.31%)  0/326 (0.00%) 
Pyelonephritis  1  0/323 (0.00%)  1/326 (0.31%) 
Pyelonephritis acute  1  1/323 (0.31%)  0/326 (0.00%) 
Sinusitis  1  0/323 (0.00%)  1/326 (0.31%) 
Urinary tract infection  1  0/323 (0.00%)  1/326 (0.31%) 
Urosepsis  1  0/323 (0.00%)  1/326 (0.31%) 
Injury, poisoning and procedural complications     
Clavicle fracture  1  0/323 (0.00%)  1/326 (0.31%) 
Contusion  1  0/323 (0.00%)  1/326 (0.31%) 
Femur fracture  1  2/323 (0.62%)  0/326 (0.00%) 
Head injury  1  1/323 (0.31%)  1/326 (0.31%) 
Joint injury  1  1/323 (0.31%)  0/326 (0.00%) 
Limb injury  1  0/323 (0.00%)  1/326 (0.31%) 
Muscle rupture  1  0/323 (0.00%)  1/326 (0.31%) 
Pelvic fracture  1  0/323 (0.00%)  1/326 (0.31%) 
Tendon rupture  1  1/323 (0.31%)  0/326 (0.00%) 
Investigations     
Blood pressure decreased  1  0/323 (0.00%)  1/326 (0.31%) 
Intraocular pressure increased (Fellow eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Intraocular pressure increased (Study eye)  1  0/323 (0.00%)  1/326 (0.31%) 
Metabolism and nutrition disorders     
Dehydration  1  0/323 (0.00%)  1/326 (0.31%) 
Hypercreatininaemia  1  1/323 (0.31%)  0/326 (0.00%) 
Hypokalaemia  1  1/323 (0.31%)  0/326 (0.00%) 
Hyponatraemia  1  1/323 (0.31%)  0/326 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  1/323 (0.31%)  0/326 (0.00%) 
Pathological fracture  1  1/323 (0.31%)  0/326 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  0/323 (0.00%)  1/326 (0.31%) 
Colon cancer  1  1/323 (0.31%)  0/326 (0.00%) 
Gastrointestinal carcinoma  1  1/323 (0.31%)  0/326 (0.00%) 
Lung cancer metastatic  1  1/323 (0.31%)  0/326 (0.00%) 
Lung neoplasm malignant  1  0/323 (0.00%)  2/326 (0.61%) 
Non-small cell lung cancer metastatic  1  1/323 (0.31%)  0/326 (0.00%) 
Ovarian cancer  1  0/323 (0.00%)  1/326 (0.31%) 
Renal cancer  1  1/323 (0.31%)  0/326 (0.00%) 
Thyroid neoplasm  1  0/323 (0.00%)  1/326 (0.31%) 
Nervous system disorders     
Carotid artery thrombosis  1  1/323 (0.31%)  0/326 (0.00%) 
Cerebrovascular accident  1  0/323 (0.00%)  2/326 (0.61%) 
Dizziness  1  0/323 (0.00%)  1/326 (0.31%) 
Hemiparesis  1  1/323 (0.31%)  0/326 (0.00%) 
Intracranial aneurysm  1  1/323 (0.31%)  0/326 (0.00%) 
Loss of consciousness  1  0/323 (0.00%)  1/326 (0.31%) 
Monoparesis  1  0/323 (0.00%)  1/326 (0.31%) 
Sciatica  1  0/323 (0.00%)  2/326 (0.61%) 
Syncope  1  1/323 (0.31%)  1/326 (0.31%) 
Transient ischaemic attack  1  3/323 (0.93%)  1/326 (0.31%) 
VIth nerve paresis  1  0/323 (0.00%)  1/326 (0.31%) 
Renal and urinary disorders     
Acute kidney injury  1  0/323 (0.00%)  1/326 (0.31%) 
Bladder prolapse  1  0/323 (0.00%)  1/326 (0.31%) 
Haematuria  1  1/323 (0.31%)  0/326 (0.00%) 
Hydronephrosis  1  1/323 (0.31%)  0/326 (0.00%) 
Nephrolithiasis  1  1/323 (0.31%)  1/326 (0.31%) 
Urinary incontinence  1  1/323 (0.31%)  0/326 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/323 (0.00%)  1/326 (0.31%) 
Choking  1  0/323 (0.00%)  1/326 (0.31%) 
Chronic obstructive pulmonary disease  1  2/323 (0.62%)  1/326 (0.31%) 
Dyspnoea  1  2/323 (0.62%)  1/326 (0.31%) 
Epistaxis  1  1/323 (0.31%)  0/326 (0.00%) 
Pulmonary congestion  1  1/323 (0.31%)  0/326 (0.00%) 
Respiratory failure  1  1/323 (0.31%)  0/326 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/323 (0.31%)  1/326 (0.31%) 
Hypertensive crisis  1  1/323 (0.31%)  0/326 (0.00%) 
Hypotension  1  2/323 (0.62%)  0/326 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Group I Ranibizumab 0.5 mg TER Group II Ranibizumab 0.5 mg Monthly
Affected / at Risk (%) Affected / at Risk (%)
Total   164/323 (50.77%)   166/326 (50.92%) 
Eye disorders     
Age-related macular degeneration (Fellow eye)  1  9/323 (2.79%)  4/326 (1.23%) 
Blepharitis (Fellow eye)  1  6/323 (1.86%)  8/326 (2.45%) 
Blepharitis (Study eye)  1  5/323 (1.55%)  6/326 (1.84%) 
Cataract (Fellow eye)  1  7/323 (2.17%)  10/326 (3.07%) 
Cataract (Study eye)  1  7/323 (2.17%)  7/326 (2.15%) 
Choroidal neovascularisation (Fellow eye)  1  6/323 (1.86%)  7/326 (2.15%) 
Conjunctival haemorrhage (Study eye)  1  14/323 (4.33%)  19/326 (5.83%) 
Detachment of retinal pigment epithelium (Study eye)  1  0/323 (0.00%)  4/326 (1.23%) 
Dry eye (Fellow eye)  1  7/323 (2.17%)  6/326 (1.84%) 
Dry eye (Study eye)  1  6/323 (1.86%)  7/326 (2.15%) 
Eye pain (Study eye)  1  10/323 (3.10%)  5/326 (1.53%) 
Neovascular age-related macular degeneration (Fellow eye)  1  8/323 (2.48%)  16/326 (4.91%) 
Ocular hypertension (Study eye)  1  4/323 (1.24%)  4/326 (1.23%) 
Punctate keratitis (Study eye)  1  4/323 (1.24%)  3/326 (0.92%) 
Retinal haemorrhage (Study eye)  1  5/323 (1.55%)  8/326 (2.45%) 
Retinal pigment epithelial tear (Study eye)  1  4/323 (1.24%)  3/326 (0.92%) 
Visual acuity reduced (Fellow eye)  1  6/323 (1.86%)  4/326 (1.23%) 
Visual acuity reduced (Study eye)  1  15/323 (4.64%)  12/326 (3.68%) 
Vitreous floaters (Study eye)  1  1/323 (0.31%)  4/326 (1.23%) 
Gastrointestinal disorders     
Nausea  1  4/323 (1.24%)  5/326 (1.53%) 
General disorders     
Oedema peripheral  1  0/323 (0.00%)  5/326 (1.53%) 
Infections and infestations     
Bronchitis  1  6/323 (1.86%)  12/326 (3.68%) 
Conjunctivitis (Fellow eye)  1  6/323 (1.86%)  6/326 (1.84%) 
Conjunctivitis (Study eye)  1  10/323 (3.10%)  6/326 (1.84%) 
Cystitis  1  3/323 (0.93%)  4/326 (1.23%) 
Influenza  1  9/323 (2.79%)  12/326 (3.68%) 
Nasopharyngitis  1  18/323 (5.57%)  26/326 (7.98%) 
Respiratory tract infection  1  5/323 (1.55%)  3/326 (0.92%) 
Sinusitis  1  1/323 (0.31%)  4/326 (1.23%) 
Urinary tract infection  1  5/323 (1.55%)  2/326 (0.61%) 
Investigations     
Blood pressure increased  1  4/323 (1.24%)  1/326 (0.31%) 
Intraocular pressure increased (Fellow eye)  1  3/323 (0.93%)  8/326 (2.45%) 
Intraocular pressure increased (Study eye)  1  27/323 (8.36%)  28/326 (8.59%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/323 (1.24%)  6/326 (1.84%) 
Back pain  1  4/323 (1.24%)  5/326 (1.53%) 
Osteoarthritis  1  4/323 (1.24%)  4/326 (1.23%) 
Nervous system disorders     
Dizziness  1  5/323 (1.55%)  1/326 (0.31%) 
Headache  1  4/323 (1.24%)  4/326 (1.23%) 
Sciatica  1  6/323 (1.86%)  1/326 (0.31%) 
Psychiatric disorders     
Depression  1  2/323 (0.62%)  4/326 (1.23%) 
Insomnia  1  5/323 (1.55%)  0/326 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  4/323 (1.24%)  0/326 (0.00%) 
Cough  1  5/323 (1.55%)  2/326 (0.61%) 
Oropharyngeal pain  1  2/323 (0.62%)  6/326 (1.84%) 
Vascular disorders     
Hypertension  1  23/323 (7.12%)  13/326 (3.99%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
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 or disclosure of trial results in their entirety
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01948830     History of Changes
Other Study ID Numbers: CRFB002A2411
2013-002626-23 ( EudraCT Number )
First Submitted: September 19, 2013
First Posted: September 24, 2013
Results First Submitted: October 19, 2016
Results First Posted: December 15, 2016
Last Update Posted: April 17, 2017