Diabetic Retinopathy
Conditions
Keywords
Diabetic macular edema, Visual impairment
Brief summary
The purpose of this study was to demonstrate that the change of best corrected visual acuity (BCVA) was comparable in patients treated with ranibizumab at the discretion of the investigator vs. treatment according to a standard of care scheme (pro re nata, as needed).
Interventions
intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤ 12.0% * Patients with visual impairment due to DME in at least one eye * BCVA ≥ 24 and ≤ 78 letters in the study eye
Exclusion criteria
* Active intraocular inflammation * Any active infection in either eye at the * Structural damage within 0.5 disc diameter of the center of the macula in the study eye * Uncontrolled glaucoma in either eye at screening Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 | BCVA was assessed as letters read using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The mean average change from baseline was defined as the difference between the average level of BCVA (ETDRS letters) over all post-baseline assessments from Month 1 to Month 12. A positive change represents an improvement in visual acuity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Injections | Baseline to Month 12 | mean number of injections in the study eye during the study |
| Number of Treatment Free Intervals | Baseline to Month 12 | A treatment-free interval is the interval between the first NO treatment given when the reason for NO treatment given is one of the three stability criteria and the first subsequent YES treatment given after that. |
| Number of Visits | Baseline to Month 12 | Mean number of visits during the study |
| Mean Change of Foveal Center Point Thickness | Baseline to Month 12 | Evaluated by central reading center assessing OCT images |
| Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | Baseline to Month 12 | Evaluated by central reading center scoring fundus photography |
| Mean Change in Central Subfield Retinal Thickness (CSRT) | Baseline to Month 12 | Evaluated by central reading center assessing OCT images |
Countries
Germany
Participant flow
Recruitment details
a total of 135 patients were randomized and assigned in a 1:1 ratio to the treatment arms.
Pre-assignment details
At Screening, the eligibility criteria were performed.
Participants by arm
| Arm | Count |
|---|---|
| Discretion of the Investigator (DI) Investigational - ranibizumab 0.5 mg | 67 |
| Pro re Nata (PRN) Standard of Care - ranibizumab 0.5 mg | 66 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
Baseline characteristics
| Characteristic | Pro re Nata (PRN) | Discretion of the Investigator (DI) | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 10.37 | 62.6 years STANDARD_DEVIATION 13.73 | 63.8 years STANDARD_DEVIATION 12.19 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 64 Participants | 64 Participants | 128 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 25 Participants | 22 Participants | 47 Participants |
| Sex: Female, Male Male | 41 Participants | 45 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 68 | 2 / 67 |
| other Total, other adverse events | 44 / 68 | 43 / 67 |
| serious Total, serious adverse events | 13 / 68 | 22 / 67 |
Outcome results
Primary
Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12)
BCVA was assessed as letters read using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The mean average change from baseline was defined as the difference between the average level of BCVA (ETDRS letters) over all post-baseline assessments from Month 1 to Month 12. A positive change represents an improvement in visual acuity
Time frame: Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Population: FAS - Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Discretion of the Investigator (DI) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | Baseline (Day 1) | 67.4 Letters | Standard Deviation 9.52 |
| Discretion of the Investigator (DI) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | post baseline average over month 1 to month 12 | 73.5 Letters | Standard Deviation 9.5 |
| Discretion of the Investigator (DI) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | Visit-averaged change from baseline | 6.1 Letters | Standard Deviation 6.54 |
| Pro re Nata (PRN) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | Baseline (Day 1) | 65.1 Letters | Standard Deviation 9.59 |
| Pro re Nata (PRN) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | post baseline average over month 1 to month 12 | 73.8 Letters | Standard Deviation 7.75 |
| Pro re Nata (PRN) | Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) | Visit-averaged change from baseline | 8.6 Letters | Standard Deviation 6.45 |
Comparison: The primary objective was to demonstrate that the mean visit-averaged change from baseline of BCVA over month 1 to treatment completion for the DI arm was non-inferior to the PRN arm.p-value: 0.00295% CI: [-3.04, 1.27]ANCOVA
Secondary
Mean Change in Central Subfield Retinal Thickness (CSRT)
Evaluated by central reading center assessing OCT images
Time frame: Baseline to Month 12
Population: FAS - Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Discretion of the Investigator (DI) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Baseline | 420.0 μm | Standard Deviation 114.98 |
| Discretion of the Investigator (DI) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Month 12 (LOCF) | 313.3 μm | Standard Deviation 61.21 |
| Discretion of the Investigator (DI) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Change from Baseline to Month 12 (LOCF) | -106.7 μm | Standard Deviation 109.58 |
| Pro re Nata (PRN) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Baseline | 431.0 μm | Standard Deviation 128.13 |
| Pro re Nata (PRN) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Month 12 (LOCF) | 320.6 μm | Standard Deviation 85.27 |
| Pro re Nata (PRN) | Mean Change in Central Subfield Retinal Thickness (CSRT) | Change from Baseline to Month 12 (LOCF) | -110.4 μm | Standard Deviation 101.97 |
p-value: 0.6295% CI: [-17.1, 28.56]ANCOVA
Secondary
Mean Change of Foveal Center Point Thickness
Evaluated by central reading center assessing OCT images
Time frame: Baseline to Month 12
Population: FAS - LOCF - including only patients with assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Discretion of the Investigator (DI) | Mean Change of Foveal Center Point Thickness | Baseline | 398.8 μm | Standard Deviation 144.1 |
| Discretion of the Investigator (DI) | Mean Change of Foveal Center Point Thickness | Month 12 - LOCF | 273.3 μm | Standard Deviation 84.85 |
| Discretion of the Investigator (DI) | Mean Change of Foveal Center Point Thickness | Change from Baseline to Month 12 (LOCF) | -125.6 μm | Standard Deviation 142.69 |
| Pro re Nata (PRN) | Mean Change of Foveal Center Point Thickness | Baseline | 405.0 μm | Standard Deviation 138.06 |
| Pro re Nata (PRN) | Mean Change of Foveal Center Point Thickness | Month 12 - LOCF | 280.6 μm | Standard Deviation 105.44 |
| Pro re Nata (PRN) | Mean Change of Foveal Center Point Thickness | Change from Baseline to Month 12 (LOCF) | -124.4 μm | Standard Deviation 113.29 |
p-value: 0.92595% CI: [-33.66, 30.59]ANCOVA
Secondary
Number of Injections
mean number of injections in the study eye during the study
Time frame: Baseline to Month 12
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discretion of the Investigator (DI) | Number of Injections | 8.4 Injections | Standard Deviation 2.98 |
| Pro re Nata (PRN) | Number of Injections | 7.8 Injections | Standard Deviation 3.25 |
Secondary
Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale
Evaluated by central reading center scoring fundus photography
Time frame: Baseline to Month 12
Population: FAS - LOCF - including only patients with assessments
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 1 step loss | 4 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 2 steps improvement | 3 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 2 steps loss | 2 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | > 2 steps improvement | 7 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | > 2 steps loss | 1 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 0 steps | 38 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | Missing | 6 Participants |
| Discretion of the Investigator (DI) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 1 step improvement | 6 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | Missing | 10 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | > 2 steps improvement | 7 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 1 step improvement | 1 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 0 steps | 34 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 1 step loss | 4 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 2 steps loss | 1 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | > 2 steps loss | 5 Participants |
| Pro re Nata (PRN) | Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale | 2 steps improvement | 4 Participants |
Secondary
Number of Treatment Free Intervals
A treatment-free interval is the interval between the first NO treatment given when the reason for NO treatment given is one of the three stability criteria and the first subsequent YES treatment given after that.
Time frame: Baseline to Month 12
Population: FAS - including only patients with at least one treatment-free interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discretion of the Investigator (DI) | Number of Treatment Free Intervals | 1.6 Intervals | Standard Deviation 0.76 |
| Pro re Nata (PRN) | Number of Treatment Free Intervals | 1.7 Intervals | Standard Deviation 0.94 |
Secondary
Number of Visits
Mean number of visits during the study
Time frame: Baseline to Month 12
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discretion of the Investigator (DI) | Number of Visits | 12.7 Visits | Standard Deviation 1.92 |
| Pro re Nata (PRN) | Number of Visits | 12.9 Visits | Standard Deviation 2.25 |