Diabetic Macular Edema
Conditions
Keywords
DME, Diabetic macular edema, ranibizumab, Diabetic macular edema with center involvement
Brief summary
This study evaluated the safety and efficacy of ranibizumab on retinal edema and visual acuity in patients with diabetic macular edema with center involvement.
Interventions
6 mg/ml ranibizumab solution for intravitreal injection
10 mg/ml ranibizumab solution for intravitreal injection
DRUGSham injection
Non-treatment control for sham intravitreal injection.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diabetic macular edema with center involvement in at least one eye * Type 1 or type 2 diabetes mellitus diagnosed 2 years prior to screening * Laser photocoagulation in the study eye can be withheld for at least 3 months after randomization
Exclusion criteria
* Patients with uncontrolled systemic or ocular diseases * Have any history of any intraocular surgery in the study eye within the past 6 months preceding screening * Conditions that require chronic concomitant therapy with systemic or topical ocular corticosteroids Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12 | Baseline through the end of study (Month 12) | Visual acuity (VA) was assessed on both eyes 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 as described in the Study Operations Manual. |
| Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12 | Baseline through the end of study (Month 12) | Visual acuity (VA) was assessed on both eyes 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 as described in the Study Operations Manual. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12 | Baseline through the end of study (Month 12) | Optical Coherence Tomography (OCT) was assessed on both eyes at every study visit. These assessments were performed by trained personnel at the sites. OCT imaging was performed using the Zeiss Humphrey System Model 2000 (or later) with version A6.1 software running under Windows 95 or Windows 98. The analysis of the OCT images were performed by the Photographic Reading Center which provided a study manual and training materials. OCT operators, systems and software were certified prior to any evaluation of study patients. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.3 mg Participants received monthly intravitreal injections with 0.3 mg ranibizumab (6 mg/ml) for up to 12 months. At each monthly visit from month 1 and onwards, the evaluating physician decided whether an increase in the dose to 0.6 mg was needed according to set criteria. If the dose was increased, all subsequent administrations were of the higher dose unless treatment had been withheld for more than 45 days (for any reason), in which case injections restarted with the initial dose. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | 51 |
| Ranibizumab 0.5 mg Participants received monthly intravitreal injections with 0.5 mg ranibizumab (10 mg/ml) for up to 12 months. At each monthly visit from month 1 and onwards, the evaluating physician decided whether an increase in the dose to 1.0 mg was needed according to set criteria. If the dose was increased, all subsequent administrations were of the higher dose unless treatment had been withheld for more than 45 days (for any reason), in which case injections restarted with the initial dose. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | 51 |
| Sham Injection Participants in the control group received 12 monthly sham intravitreal injections. The evaluation was performed using the same criteria for dose doubling as in active treatment groups. The injection was a mimicked by an empty syringe without a needle. Laser photocoagulation was permitted as rescue treatment for the study eye after 3 consecutive monthly injections. | 49 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Ranibizumab 0.3 mg | Ranibizumab 0.5 mg | Sham Injection | Total |
|---|---|---|---|---|
| Age Continuous | 63.2 years STANDARD_DEVIATION 10.44 | 62.8 years STANDARD_DEVIATION 10.14 | 65.0 years STANDARD_DEVIATION 9.26 | 63.6 years STANDARD_DEVIATION 9.95 |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 24 Participants | 70 Participants |
| Sex: Female, Male Male | 29 Participants | 27 Participants | 25 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 51 | 43 / 51 | 32 / 49 |
| serious Total, serious adverse events | 9 / 51 | 9 / 51 | 9 / 49 |
Outcome results
Primary
Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12
Visual acuity (VA) was assessed on both eyes 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 as described in the Study Operations Manual.
Time frame: Baseline through the end of study (Month 12)
Population: Full Analysis Set (FAS): All patients who received at least one application of study treatment and had at least one post-baseline assessment for BCVA. A Last Observation Carried Forward (LOCF) approach was used; missing values were replaced by the mean of the last observation before and the first observation after the missing time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg | Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12 | 9.2 Letters | Standard Deviation 5.6 |
| Ranibizumab 0.5 mg | Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12 | 6.4 Letters | Standard Deviation 9.21 |
| Sham Injection | Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12 | -0.1 Letters | Standard Deviation 9.77 |
Primary
Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12
Visual acuity (VA) was assessed on both eyes 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 as described in the Study Operations Manual.
Time frame: Baseline through the end of study (Month 12)
Population: Full Analysis Set (FAS): All patients who received at least one application of study treatment and had at least one post-baseline assessment for BCVA. A Last Observation Carried Forward (LOCF) approach was used; missing values were replaced by the mean of the last observation before and the first observation after the missing time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg | Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12 | 11.8 Letters | Standard Deviation 6.59 |
| Ranibizumab 0.5 mg | Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12 | 8.8 Letters | Standard Deviation 10.99 |
| Sham Injection | Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye at Month 12 | -1.4 Letters | Standard Deviation 14.16 |
Secondary
Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12
Optical Coherence Tomography (OCT) was assessed on both eyes at every study visit. These assessments were performed by trained personnel at the sites. OCT imaging was performed using the Zeiss Humphrey System Model 2000 (or later) with version A6.1 software running under Windows 95 or Windows 98. The analysis of the OCT images were performed by the Photographic Reading Center which provided a study manual and training materials. OCT operators, systems and software were certified prior to any evaluation of study patients.
Time frame: Baseline through the end of study (Month 12)
Population: Full Analysis Set (FAS): All patients who received at least one application of study treatment and had at least one post-baseline assessment for BCVA. A Last Observation Carried Forward (LOCF) approach was used; missing values were replaced by the mean of the last observation before and the first observation after the missing time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg | Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12 | -200.7 µm | Standard Deviation 122.18 |
| Ranibizumab 0.5 mg | Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12 | -187.6 µm | Standard Deviation 147.82 |
| Sham Injection | Mean Change From Baseline in Central Retinal Thickness (µm) of the Study Eye at Month 12 | -48.4 µm | Standard Deviation 153.43 |