Diabetic Macular Edema, Visual Impairment
Conditions
Keywords
Diabetic Macular Edema, Ranibizumab, Laser Treatment, Visual impairment
Brief summary
This study will assess the efficacy and safety of ranibizumab (intravitreal injections) versus laser treatment in patients with visual impairment due to diabetic macular edema.
Interventions
DRUGRFB002
0.5 mg
PROCEDURELaser photocoagulation
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diabetes mellitus 1 or 2, HbA1c \< 11.0%, With: Clinically significant Diabetic Macular Edema in at least one eye. 2. Previous treatment with macular photocoagulation only should be considered if the investigator believes that the study eye may possibly benefit from additional photocoagulation. 3. Best corrected visual acuity score between 78 and 25 letters (Early Treatment Diabetic Retinopathy Study- ETDRS Chart - 4 meters). 4. Central foveal thickness \>250µm (Optical Coherence Tomography). 5. Diabetes medication stable in the 3 months prior.
Exclusion criteria
In the study eye: 1. Active intraocular inflammation. 2. Any active infection. 3. History of uveitis. 4. Structural damage within 500 microns of the center of the macula. 5. Neovascularization of the iris. 6. Uncontrolled glaucoma in either eye (Intraocular Pressure \> 24 mmHg). Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | Baseline, 12 months | Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement in BCVA | 12 months | Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. |
| Evolution of Mean Change From Baseline in BCVA by Study Visit | Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. |
| Percentage of Participants With VA > 73 Letters With Ranibizumab (0.5 mg) vs Laser. | 12 months | VA 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. |
| Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | CRT was assessed by Optical Coherence Tomography (OCT). |
| Percentage of CRT Change From Baseline by Study Visit | Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | CRT was assessed by Optical Coherence Tomography (OCT). |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RFB002 RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved. | 39 |
| Laser Photocoagulation At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4. | 43 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory values | 0 | 1 |
| Overall Study | Administration problems | 0 | 1 |
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol deviations | 5 | 4 |
Baseline characteristics
| Characteristic | RFB002 | Laser Photocoagulation | Total |
|---|---|---|---|
| Age, Continuous | 61.31 Years STANDARD_DEVIATION 8.94 | 65.47 Years STANDARD_DEVIATION 9.4 | 63.49 Years STANDARD_DEVIATION 9.36 |
| Sex: Female, Male Female | 15 Participants | 18 Participants | 33 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 39 | 3 / 43 |
| serious Total, serious adverse events | 3 / 39 | 2 / 43 |
Outcome results
Primary
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA)
Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time frame: Baseline, 12 months
Population: Intent-to-treat (ITT): The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. Participants who had both Baseline and Month 12 BCVA values only were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RFB002 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 9.41 letters | Standard Deviation 9.15 |
| Laser Photocoagulation | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 5.79 letters | Standard Deviation 9.4 |
Secondary
Evolution of Mean Change From Baseline in BCVA by Study Visit
Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: ITT: The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. For each month, participants who had both the baseline and the study month BCVA values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 1 (n=34,38) | 4.56 letters | Standard Deviation 7.38 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 2 (n=31,38) | 4.61 letters | Standard Deviation 6.55 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 3 (n=33,38) | 6.24 letters | Standard Deviation 6.41 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 4 (n=33,37) | 6.33 letters | Standard Deviation 7.4 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 5 (n=31,37) | 7.03 letters | Standard Deviation 8 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 6 (n=33,35) | 7.61 letters | Standard Deviation 6.88 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 7 (n=33,33) | 7.91 letters | Standard Deviation 7.16 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 8 (n=32,34) | 8.00 letters | Standard Deviation 7.77 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 9 (n=32,33) | 8.44 letters | Standard Deviation 8.78 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 10 (n=31,32) | 7.32 letters | Standard Deviation 8.17 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 11 (n=32,32) | 7.69 letters | Standard Deviation 8.88 |
| RFB002 | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 12 (n=32,33) | 9.41 letters | Standard Deviation 9.15 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 10 (n=31,32) | 5.84 letters | Standard Deviation 9.14 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 1 (n=34,38) | 1.32 letters | Standard Deviation 7.99 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 7 (n=33,33) | 3.85 letters | Standard Deviation 7.97 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 2 (n=31,38) | 1.89 letters | Standard Deviation 8.04 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 12 (n=32,33) | 5.79 letters | Standard Deviation 9.4 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 3 (n=33,38) | 3.11 letters | Standard Deviation 7.83 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 11 (n=32,32) | 6.44 letters | Standard Deviation 8.32 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 4 (n=33,37) | 2.76 letters | Standard Deviation 8.66 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 9 (n=32,33) | 6.00 letters | Standard Deviation 9.81 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 5 (n=31,37) | 3.38 letters | Standard Deviation 8.95 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 8 (n=32,34) | 3.21 letters | Standard Deviation 7.75 |
| Laser Photocoagulation | Evolution of Mean Change From Baseline in BCVA by Study Visit | Month 6 (n=33,35) | 4.11 letters | Standard Deviation 7.65 |
Secondary
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit
CRT was assessed by Optical Coherence Tomography (OCT).
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: ITT: The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. For each month, participants who had both the baseline and the study month CRT values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 1 (n=33,37) | -50.18 micrometers | Standard Deviation 62.23 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 2 (n=31,38) | -69.52 micrometers | Standard Deviation 65.1 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 5 (n=30,37) | -77.77 micrometers | Standard Deviation 73.47 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 6 (n=33,34) | -93.73 micrometers | Standard Deviation 79.42 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 10 (n=31,31) | -83.32 micrometers | Standard Deviation 81.56 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 11 (n=32,33) | -98.03 micrometers | Standard Deviation 76.75 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 12 (n=32,33) | -76.28 micrometers | Standard Deviation 76.56 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 3 (n=33,37) | -80.64 micrometers | Standard Deviation 87.06 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 4 (n=33,38) | -81.79 micrometers | Standard Deviation 92.14 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 7 (n=33,35) | -92.76 micrometers | Standard Deviation 79.55 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 8 (n=32,34) | -92.41 micrometers | Standard Deviation 82.27 |
| RFB002 | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 9 (n=32,34) | -81.59 micrometers | Standard Deviation 81.38 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 11 (n=32,33) | -94.85 micrometers | Standard Deviation 114.67 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 1 (n=33,37) | -21.86 micrometers | Standard Deviation 82.86 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 4 (n=33,38) | -37.66 micrometers | Standard Deviation 83.29 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 2 (n=31,38) | -14.21 micrometers | Standard Deviation 66.95 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 12 (n=32,33) | -86.00 micrometers | Standard Deviation 115.53 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 5 (n=30,37) | -28.92 micrometers | Standard Deviation 91.51 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 8 (n=32,34) | -64.82 micrometers | Standard Deviation 110.05 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 6 (n=33,34) | -40.47 micrometers | Standard Deviation 100.12 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 9 (n=32,34) | -74.59 micrometers | Standard Deviation 112.75 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 3 (n=33,37) | -43.16 micrometers | Standard Deviation 89.74 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 10 (n=31,31) | -84.39 micrometers | Standard Deviation 102.79 |
| Laser Photocoagulation | Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit | Month 7 (n=33,35) | -60.94 micrometers | Standard Deviation 110.05 |
Secondary
Percentage of CRT Change From Baseline by Study Visit
CRT was assessed by Optical Coherence Tomography (OCT).
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: ITT: The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. For each month, participants who had both the baseline and the study month CRT values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 1 (n=33,37) | -12.06 Percentage change | Standard Deviation 15.16 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 2 (n=31,38) | -15.61 Percentage change | Standard Deviation 13.9 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 3 (n=33,37) | -18.25 Percentage change | Standard Deviation 17.09 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 4 (n=33,38) | -18.00 Percentage change | Standard Deviation 17.93 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 5 (n=30,37) | -18.21 Percentage change | Standard Deviation 15.68 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 6 (n=33,34) | -20.69 Percentage change | Standard Deviation 15.85 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 7 (n=33,35) | -21.11 Percentage change | Standard Deviation 15.68 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 8 (n=32,34) | -21.20 Percentage change | Standard Deviation 16.43 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 9 (n=32,34) | -19.17 Percentage change | Standard Deviation 17.95 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 10 (n=31,31) | -19.55 Percentage change | Standard Deviation 17.34 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 11 (n=32,33) | -22.65 Percentage change | Standard Deviation 15.85 |
| RFB002 | Percentage of CRT Change From Baseline by Study Visit | Month 12 (n=32,33) | -18.23 Percentage change | Standard Deviation 16.66 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 11 (n=32,33) | -19.04 Percentage change | Standard Deviation 22.31 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 1 (n=33,37) | -3.01 Percentage change | Standard Deviation 17.52 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 7 (n=33,35) | -12.50 Percentage change | Standard Deviation 23.05 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 2 (n=31,38) | -2.20 Percentage change | Standard Deviation 15.24 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 10 (n=31,31) | -17.24 Percentage change | Standard Deviation 19.63 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 3 (n=33,37) | -7.97 Percentage change | Standard Deviation 17.8 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 8 (n=32,34) | -13.02 Percentage change | Standard Deviation 20.95 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 4 (n=33,38) | -6.99 Percentage change | Standard Deviation 17.18 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 12 (n=32,33) | -16.59 Percentage change | Standard Deviation 25.06 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 5 (n=30,37) | -6.39 Percentage change | Standard Deviation 19.27 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 9 (n=32,34) | -15.68 Percentage change | Standard Deviation 21.87 |
| Laser Photocoagulation | Percentage of CRT Change From Baseline by Study Visit | Month 6 (n=33,34) | -8.55 Percentage change | Standard Deviation 21.06 |
Secondary
Percentage of Participants With Improvement in BCVA
Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time frame: 12 months
Population: Intent-to-treat (ITT): The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RFB002 | Percentage of Participants With Improvement in BCVA | 74.29 Percentage of participants |
| Laser Photocoagulation | Percentage of Participants With Improvement in BCVA | 68.42 Percentage of participants |
Secondary
Percentage of Participants With VA > 73 Letters With Ranibizumab (0.5 mg) vs Laser.
VA 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.
Time frame: 12 months
Population: Intent-to-treat (ITT): The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RFB002 | Percentage of Participants With VA > 73 Letters With Ranibizumab (0.5 mg) vs Laser. | 54.29 Percentage of participants |
| Laser Photocoagulation | Percentage of Participants With VA > 73 Letters With Ranibizumab (0.5 mg) vs Laser. | 23.68 Percentage of participants |