Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 24 Month Open-label, Multicenter, Phase IIIb Study of the Efficacy and Safety of Lucentis® (Ranibizumab 0,5mg) in Diabetic Patients With Visual Impairment Due to Macular Edema Evaluating a Spaced Out Follow-up After Intensive Loading Phase

Conditions
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Diabetes, Macular Edema, Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab 0.5mg


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 0.5mg<br>Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN) | Drug: Ranibizumab 0.5mg<br>* Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 6 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | Month 11 and 24 | 
| 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. | Baseline, Month 3, 6, 8 and 11 | 
| 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. | Baseline, Months 3, 6, 8 and 11 | 
| 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. | Months 6, 8 and 11 | 
| 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. | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 | 
| 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]). | Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11 | 
| 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. | Baseline, Months 3, 6, 8 and 11 | 
| 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]). | Baseline, Months 3, 6, 8 and 11 | 
| 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. | baseline, months 11, 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ranibizumab, Diabetic Macular Edema