Diabetes, Macular Degeneration, Macular Edema
Conditions
Keywords
Ranibizumab, Diabetic Macular Edema
Brief summary
The study was designed to assess the efficacy and safety of Lucentis® (ranibizumab 0.5 mg) in diabetic patients presenting with reduced visual acuity due to diabetic macular edema and evaluating spacing out of follow-up after initial intensive treatment phase.
Detailed description
This was a multicenteric, open-label, phase IIIb study, which comprised of 2 groups: the Main Group and the Rescue Group. Patient's eligibility was assessed during a screening visit (Visit 1) which took place 14 days maximum before treatment initiation (Visit 2 \[Day 0\]). All patients were initially included in the Main Group and were to receive an initial loading treatment (6 injections during the intensive treatment phase i.e. every month from Day 0 to Month 5, followed by 2 additional injections at Months 8 and 11). Patients were to be followed-up every 3 months for 18 months (spaced-out follow-up period). Their visual acuity was to be checked at each study visit (Months 3, 6, 8, 11, 14, 17, 20, and 23) to assess their response to treatment. Patients who responded to treatment were maintained in the Main Group. Patients who did not meet pre defined criteria were moved to the Rescue Group and treated at the investigator's discretion. The trial was terminated before any patient reached month 12.
Interventions
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type I or type II diabetes with HbA1c≤10% * Visual impairment due to a diabetic macular edema * Stable antidiabetic treatment (since more than 3 months) or hygiene-dietary
Exclusion criteria
* Inflammation or infection in one eye * Women of childbearing potential without an efficient contraception, pregnant or breastfeeding Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months | Month 6 and 24 | Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters | Baseline, Month 3, 6, 8 and 11 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥10 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported. |
| Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters | Baseline, Months 3, 6, 8 and 11 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥15 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported. |
| Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye. | Months 6, 8 and 11 | Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. Number of participants presenting with a ≥15 letter loss in BCVA (compared to the value observed at 6 months) and leading to a treatment change (Rescue Group) for month 8 and 11 were analyzed. |
| Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Main Group. |
| Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months | Month 11 and 24 | Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 11 months minus BCVA score at 24 months ≤4 letters) was calculated as well as its confidence interval at 95%. |
| Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group | Baseline, Months 3, 6, 8 and 11 | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Rescue Group. |
| Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group | Baseline, Months 3, 6, 8 and 11 | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]). |
| Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life | baseline, months 11, 12 and 24 | The global score obtained on the Visual Function Questionnaire 25 (VFQ 25) was compared from baseline to months 11 and 24 for the Main group and from baseline to months 12 and 24 for the Rescue group. |
| Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) was measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]). |
Countries
France
Participant flow
Recruitment details
Participants were recruited from 10 centers across France.
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discontinuation due to sponsor decision | 31 |
Baseline characteristics
| Characteristic | Ranibizumab |
|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 7.08 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 12 / 31 |
| serious Total, serious adverse events | 2 / 31 |
Outcome results
Primary
Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 6 Months
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported.
Time frame: Month 6 and 24
Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Secondary
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) was measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]).
Time frame: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 1 | -0.10 log[μm/200] | Standard Deviation 0.117 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 2 | -0.12 log[μm/200] | Standard Deviation 0.122 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 3 | -0.13 log[μm/200] | Standard Deviation 0.123 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 4 | -0.13 log[μm/200] | Standard Deviation 0.104 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 5 | -0.16 log[μm/200] | Standard Deviation 0.096 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 6 | -0.15 log[μm/200] | Standard Deviation 0.12 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 8 | -0.12 log[μm/200] | Standard Deviation 0.062 |
| Ranibizumab | Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye | Month 11 | -0.13 log[μm/200] | — |
Secondary
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye - Rescue Group
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]).
Time frame: Baseline, Months 3, 6, 8 and 11
Population: Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group
Secondary
Evaluation of the Spaced Out Follow-up on Visual Functions and Quality of Life
The global score obtained on the Visual Function Questionnaire 25 (VFQ 25) was compared from baseline to months 11 and 24 for the Main group and from baseline to months 12 and 24 for the Rescue group.
Time frame: baseline, months 11, 12 and 24
Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Secondary
Number of Participants With a Stable BCVA in the Study Eye at 24 Months Compared With BCVA at 11 Months
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 11 months minus BCVA score at 24 months ≤4 letters) was calculated as well as its confidence interval at 95%.
Time frame: Month 11 and 24
Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Secondary
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Main Group.
Time frame: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11
Population: Included population with evaluable patients at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 1 | 5.45 Letters | Standard Deviation 6.444 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 2 | 5.81 Letters | Standard Deviation 7.328 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 3 | 8.05 Letters | Standard Deviation 6.704 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 4 | 9.94 Letters | Standard Deviation 5.805 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 5 | 9.88 Letters | Standard Deviation 5.29 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 6 | 11.00 Letters | Standard Deviation 8.485 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 8 | 10.40 Letters | Standard Deviation 5.413 |
| Ranibizumab | Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) | Month 11 | 10.00 Letters | — |
Secondary
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS) - Rescue Group
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Rescue Group.
Time frame: Baseline, Months 3, 6, 8 and 11
Population: Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group
Secondary
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥10 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported.
Time frame: Baseline, Month 3, 6, 8 and 11
Population: Included population with evaluable patients at specific time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters | Month 3 | 8 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters | Month 6 | 4 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters | Month 8 | 3 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters | Month 11 | 1 Participants |
Secondary
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥15 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported.
Time frame: Baseline, Months 3, 6, 8 and 11
Population: Included population with evaluable patients at specific time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters | Month 3 | 4 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters | Month 6 | 3 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters | Month 8 | 1 Participants |
| Ranibizumab | Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters | Month 11 | 0 Participants |
Secondary
Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye.
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. Number of participants presenting with a ≥15 letter loss in BCVA (compared to the value observed at 6 months) and leading to a treatment change (Rescue Group) for month 8 and 11 were analyzed.
Time frame: Months 6, 8 and 11
Population: Included population with evaluable patients at specific time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ranibizumab | Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye. | Month 6 to Month 8 | 0 Participants |
| Ranibizumab | Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye. | Month 6 to Month 11 | 0 Participants |