Trial Outcomes & Findings for A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients (NCT NCT02259088)

NCT ID: NCT02259088

Last Updated: 2019-02-01

Results Overview

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged \[(Month1+Month2+...+Month12)/12\], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

384 participants

Primary outcome timeframe

Baseline, Monthly from Month 1 through Month 12

Results posted on

2019-02-01

Participant Flow

After eligibility confirmation, patients were randomized in a 4:1 ratio to 2 treatment arms.

Participant milestones

Participant milestones
Measure
Ranibizumab (RFB002)
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Overall Study
STARTED
307
77
Overall Study
Full Analysis Set
307
77
Overall Study
Treated (Safety Analysis Set)
307
75
Overall Study
COMPLETED
279
63
Overall Study
NOT COMPLETED
28
14

Reasons for withdrawal

Reasons for withdrawal
Measure
Ranibizumab (RFB002)
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Overall Study
Adverse Event
6
4
Overall Study
Lost to Follow-up
2
0
Overall Study
Death
2
0
Overall Study
Physician Decision
5
2
Overall Study
Protocol deviation
5
0
Overall Study
Subject/guardian decision
8
8

Baseline Characteristics

A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ranibizumab (RFB002)
n=307 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=77 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Total
n=384 Participants
Total of all reporting groups
Age, Continuous
58.6 years
STANDARD_DEVIATION 8.70 • n=5 Participants
59.0 years
STANDARD_DEVIATION 9.19 • n=7 Participants
58.7 years
STANDARD_DEVIATION 8.79 • n=5 Participants
Sex: Female, Male
Female
168 Participants
n=5 Participants
38 Participants
n=7 Participants
206 Participants
n=5 Participants
Sex: Female, Male
Male
139 Participants
n=5 Participants
39 Participants
n=7 Participants
178 Participants
n=5 Participants
Best Corrected Visual Acuity
59.6 letters
STANDARD_DEVIATION 10.53 • n=5 Participants
58.2 letters
STANDARD_DEVIATION 9.43 • n=7 Participants
59.3 letters
STANDARD_DEVIATION 10.32 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Monthly from Month 1 through Month 12

Population: Full Analysis Set (FAS). Missing values imputed by the mean value last observation carried forward (MV-LOCF).

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged \[(Month1+Month2+...+Month12)/12\], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12
6.8 letters
Standard Deviation 6.58
1.1 letters
Standard Deviation 7.73

SECONDARY outcome

Timeframe: Baseline, Monthly from Month 1 through Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 1
4.0 letters
Standard Deviation 5.59
-0.9 letters
Standard Deviation 5.50
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 2
5.8 letters
Standard Deviation 6.44
0.0 letters
Standard Deviation 8.08
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 3
6.9 letters
Standard Deviation 6.91
1.1 letters
Standard Deviation 9.18
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 4
6.6 letters
Standard Deviation 7.23
0.0 letters
Standard Deviation 11.64
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 5
6.8 letters
Standard Deviation 7.41
0.6 letters
Standard Deviation 10.61
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 6
6.8 letters
Standard Deviation 8.00
0.3 letters
Standard Deviation 11.01
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 7
6.8 letters
Standard Deviation 7.95
1.3 letters
Standard Deviation 10.13
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 8
7.4 letters
Standard Deviation 8.12
1.9 letters
Standard Deviation 9.69
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 9
7.3 letters
Standard Deviation 8.18
1.8 letters
Standard Deviation 9.33
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 10
7.2 letters
Standard Deviation 8.45
1.6 letters
Standard Deviation 9.23
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 11
7.8 letters
Standard Deviation 8.55
1.7 letters
Standard Deviation 9.35
Mean Change From Baseline in BCVA (Letters) at Each Visit
Change from Baseline at Month 12
7.8 letters
Standard Deviation 8.72
2.5 letters
Standard Deviation 8.78

SECONDARY outcome

Timeframe: Baseline, Monthly from Month 1 through Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=301 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 1
-126.7 micrometers
Standard Deviation 140.59
-33.1 micrometers
Standard Deviation 113.34
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 2
-141.3 micrometers
Standard Deviation 146.15
-48.8 micrometers
Standard Deviation 133.22
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 3
-154.2 micrometers
Standard Deviation 147.94
-58.5 micrometers
Standard Deviation 157.30
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 4
-130.4 micrometers
Standard Deviation 152.60
-72.6 micrometers
Standard Deviation 149.13
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 5
-141.0 micrometers
Standard Deviation 153.28
-72.3 micrometers
Standard Deviation 150.45
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 6
-146.2 micrometers
Standard Deviation 154.87
-72.9 micrometers
Standard Deviation 152.47
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 7
-138.4 micrometers
Standard Deviation 161.04
-72.4 micrometers
Standard Deviation 150.86
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 8
-146.9 micrometers
Standard Deviation 154.68
-81.8 micrometers
Standard Deviation 151.89
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 9
-142.4 micrometers
Standard Deviation 156.03
-80.9 micrometers
Standard Deviation 157.69
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 10
-137.6 micrometers
Standard Deviation 152.73
-82.9 micrometers
Standard Deviation 166.16
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 11
-144.8 micrometers
Standard Deviation 159.87
-88.1 micrometers
Standard Deviation 170.11
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
Change from Baseline at Month 12
-146.5 micrometers
Standard Deviation 157.61
-85.9 micrometers
Standard Deviation 166.60

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12
Gain of ≥ 10 letters
40.6 percentage of participants
20.0 percentage of participants
Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12
Gain of ≥ 15 letters
18.5 percentage of participants
8.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12
Loss of < 10 letters
97.0 percentage of participants
89.3 percentage of participants
Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12
Loss of <15 letters
99.0 percentage of participants
97.3 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Percentage of Patients With BCVA ≥ 73 Letters at Month 12
36.0 percentage of participants
21.3 percentage of participants

SECONDARY outcome

Timeframe: Monthly from Month 3 through Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged \[(Month4+Month5+...+Month12)/9\],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=303 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3
Month 3
66.4 letters
Standard Deviation 10.66
59.2 letters
Standard Deviation 12.63
Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3
Average Change from Baseline Month 4 to Month 12
0.3 letters
Standard Deviation 4.51
0.2 letters
Standard Deviation 6.08

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score
Change from Baseline at Month 6
2.5 units on a scale
Standard Deviation 13.54
0.5 units on a scale
Standard Deviation 13.17
Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score
Change from Baseline at Month 12
0.6 units on a scale
Standard Deviation 14.99
-0.4 units on a scale
Standard Deviation 15.89

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12
Change from Baseline at Month 6
-1.5 units on a scale
Standard Deviation 22.32
-0.4 units on a scale
Standard Deviation 21.81
Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12
Change from Baseline at Month 12
-2.3 units on a scale
Standard Deviation 24.34
-4.3 units on a scale
Standard Deviation 26.56

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12
Change from Baseline at Month 6
6.2 units on a scale
Standard Deviation 18.77
4.7 units on a scale
Standard Deviation 19.58
Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12
Change from Baseline at Month 12
5.9 units on a scale
Standard Deviation 18.12
5.9 units on a scale
Standard Deviation 20.06

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=280 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=67 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12
Change from Baseline at Month 6
2.0 units on a scale
Standard Deviation 16.68
2.2 units on a scale
Standard Deviation 17.26
Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12
Change from Baseline at Month 12
0.2 units on a scale
Standard Deviation 21.55
1.6 units on a scale
Standard Deviation 20.35

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=291 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12
Change from Baseline at Month 6
1.4 units on a scale
Standard Deviation 20.51
5.5 units on a scale
Standard Deviation 22.38
Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12
Change from Baseline at Month 12
-2.3 units on a scale
Standard Deviation 25.07
3.1 units on a scale
Standard Deviation 27.64

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12
Change from Baseline at Month 6
-1.5 units on a scale
Standard Deviation 20.71
1.5 units on a scale
Standard Deviation 20.89
Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12
Change from Baseline at Month 12
-0.3 units on a scale
Standard Deviation 19.89
4.1 units on a scale
Standard Deviation 22.72

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=291 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12
Change from Baseline at Month 6
5.6 units on a scale
Standard Deviation 23.81
-1.7 units on a scale
Standard Deviation 24.20
Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12
Change from Baseline at Month 12
0.6 units on a scale
Standard Deviation 24.64
-3.4 units on a scale
Standard Deviation 21.93

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12
Change from Baseline at Month 6
5.4 units on a scale
Standard Deviation 20.79
-2.8 units on a scale
Standard Deviation 19.35
Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12
Change from Baseline at Month 12
1.6 units on a scale
Standard Deviation 23.74
-5.5 units on a scale
Standard Deviation 21.89

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=67 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12
Change from Baseline at Month 12
-0.8 units on a scale
Standard Deviation 21.58
-3.2 units on a scale
Standard Deviation 18.51
Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12
Change from Baseline at Month 6
2.1 units on a scale
Standard Deviation 19.24
-1.5 units on a scale
Standard Deviation 15.31

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12
Change from Baseline at Month 6
1.8 units on a scale
Standard Deviation 23.07
-0.2 units on a scale
Standard Deviation 23.58
Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12
Change from Baseline at Month 12
1.3 units on a scale
Standard Deviation 25.05
0.6 units on a scale
Standard Deviation 23.32

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12
Change from Baseline at Month 6
1.4 units on a scale
Standard Deviation 27.05
-0.4 units on a scale
Standard Deviation 24.24
Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12
Change from Baseline at Month 12
0.4 units on a scale
Standard Deviation 27.62
-1.4 units on a scale
Standard Deviation 28.36

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=292 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=68 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12
Change from Baseline at Month 6
0.2 units on a scale
Standard Deviation 27.95
-4.3 units on a scale
Standard Deviation 27.53
Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12
Change from Baseline at Month 12
0.9 units on a scale
Standard Deviation 30.47
-5.3 units on a scale
Standard Deviation 27.87

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12

Population: Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=44 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=12 Participants
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12
Change from Baseline at Month 6
2.8 units on a scale
Standard Deviation 15.87
2.8 units on a scale
Standard Deviation 20.52
Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12
Change from Baseline at Month 12
-0.2 units on a scale
Standard Deviation 12.29
4.5 units on a scale
Standard Deviation 27.98

SECONDARY outcome

Timeframe: Monthly from Month 3 through Month 12

Population: Safety Analysis Set

A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.

Outcome measures

Outcome measures
Measure
Ranibizumab (RFB002)
n=301 Participants
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward
1.6 retreatments
Standard Deviation 0.64

Adverse Events

Ranibizumab (RFB002)

Serious events: 57 serious events
Other events: 116 other events
Deaths: 0 deaths

Laser

Serious events: 15 serious events
Other events: 30 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ranibizumab (RFB002)
n=307 participants at risk
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 participants at risk
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Cardiac disorders
Acute myocardial infarction
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Angina unstable
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Arrhythmia
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Cardiac failure
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Cardiac failure acute
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Coronary artery disease
1.6%
5/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Cardiac disorders
Myocardial infarction
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Cataract (Fellow eye)
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Cataract (Study eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Diabetic retinal oedema (Fellow eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
2.7%
2/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Diabetic retinopathy (Fellow eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Eye haemorrhage (Fellow eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Glaucoma (Fellow eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Retinal detachment (Fellow eye)
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Vitreous haemorrhage (Fellow eye)
0.98%
3/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Vitreous haemorrhage (Study eye)
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Gastrointestinal disorders
Ascites
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Gastrointestinal disorders
Diarrhoea
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Gastrointestinal disorders
Pancreatitis acute
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
General disorders
Sudden death
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Hepatobiliary disorders
Hepatic cirrhosis
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Bronchitis
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Chronic sinusitis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Conjunctivitis viral (Fellow eye)
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Hepatitis B
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Herpes zoster
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Lung infection
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Nasopharyngitis
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Otitis media chronic
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Periodontitis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Pneumonia
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Respiratory tract infection
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Injury, poisoning and procedural complications
Ankle fracture
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Injury, poisoning and procedural complications
Poisoning
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
1.3%
4/307 • Day 1 through study completion, an average of 1 year
2.7%
2/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Diabetic ketoacidosis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Hypoglycaemia
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Hyponatraemia
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Polydipsia
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Type 2 diabetes mellitus
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Musculoskeletal and connective tissue disorders
Limb mass
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Musculoskeletal and connective tissue disorders
Muscular weakness
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Musculoskeletal and connective tissue disorders
Spinal flattening
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Basilar artery stenosis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Cerebral infarction
1.3%
4/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Diabetic neuropathy
0.98%
3/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Dizziness
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Facial paralysis
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Lacunar infarction
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Syncope
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Nervous system disorders
Vertebrobasilar insufficiency
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Chronic kidney disease
0.00%
0/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Diabetic nephropathy
1.6%
5/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Nephrolithiasis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Pollakiuria
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Renal arteriosclerosis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Renal artery stenosis
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders
Nasal polyps
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Skin and subcutaneous tissue disorders
Diabetic dermopathy
0.33%
1/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Skin and subcutaneous tissue disorders
Diabetic foot
0.33%
1/307 • Day 1 through study completion, an average of 1 year
2.7%
2/75 • Day 1 through study completion, an average of 1 year
Vascular disorders
Diabetic vascular disorder
0.65%
2/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Vascular disorders
Hypertension
0.65%
2/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year

Other adverse events

Other adverse events
Measure
Ranibizumab (RFB002)
n=307 participants at risk
3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
Laser
n=75 participants at risk
Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
Blood and lymphatic system disorders
Anaemia
3.3%
10/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Conjunctival haemorrhage (Study eye)
3.6%
11/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Dry eye (Fellow eye)
3.3%
10/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Dry eye (Study eye)
3.6%
11/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Vitreous haemorrhage (Fellow eye)
3.6%
11/307 • Day 1 through study completion, an average of 1 year
4.0%
3/75 • Day 1 through study completion, an average of 1 year
Eye disorders
Vitreous haemorrhage (Study eye)
1.6%
5/307 • Day 1 through study completion, an average of 1 year
4.0%
3/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Nasopharyngitis
6.5%
20/307 • Day 1 through study completion, an average of 1 year
9.3%
7/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Upper respiratory tract infection
8.5%
26/307 • Day 1 through study completion, an average of 1 year
2.7%
2/75 • Day 1 through study completion, an average of 1 year
Infections and infestations
Urinary tract infection
4.9%
15/307 • Day 1 through study completion, an average of 1 year
4.0%
3/75 • Day 1 through study completion, an average of 1 year
Investigations
Alanine aminotransferase increased
0.98%
3/307 • Day 1 through study completion, an average of 1 year
5.3%
4/75 • Day 1 through study completion, an average of 1 year
Investigations
Intraocular pressure increased (Study eye)
5.2%
16/307 • Day 1 through study completion, an average of 1 year
0.00%
0/75 • Day 1 through study completion, an average of 1 year
Metabolism and nutrition disorders
Hyperlipidaemia
2.9%
9/307 • Day 1 through study completion, an average of 1 year
4.0%
3/75 • Day 1 through study completion, an average of 1 year
Renal and urinary disorders
Diabetic nephropathy
3.3%
10/307 • Day 1 through study completion, an average of 1 year
1.3%
1/75 • Day 1 through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders
Cough
5.9%
18/307 • Day 1 through study completion, an average of 1 year
2.7%
2/75 • Day 1 through study completion, an average of 1 year
Vascular disorders
Hypertension
5.5%
17/307 • Day 1 through study completion, an average of 1 year
12.0%
9/75 • Day 1 through study completion, an average of 1 year

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee 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 (ie, data from all sites) in the clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER