A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients

Study Overview
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Brief Summary
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Study of efficacy and safety of 0.5 mg ranibizumab in Chinese patients with diabetic macular edema (DME)

Detailed Description
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The purpose of this study was to provide efficacy and safety data on 0.5 mg ranibizumab intravitreal injections compared to laser photocoagulation in Chinese patients with visual impairment due to DME. Treatment was driven by achieving vision stabilization.

Official Title
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A 12-month, Randomized, Double-masked, Multicenter, Laser-controlled Phase III Study Assessing the Efficacy and Safety of 0.5 mg Ranibizumab Dosed PRN in Subjects With Visual Impairment Due to Diabetic Macular Edema in Chinese Patients

Conditions
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Diabetic Macular Edema, Visual Impairment

Intervention / Treatment
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* Drug: Ranibizumab (RFB002)
* Procedure: Laser
* Drug: Sham injection
* Procedure: Sham laser


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female Chinese patients ≥ 18 years of age with diabetes mellitus and with HbA1c ≤10.0% Stable medication for diabetes within 3 months prior to Visit 1 Visual impairment due to DME with BCVA score between 78 and 39 letters as measured by ETDRS-like charts at 4 meters Key Exclusion Criteria: Stroke or myocardial infarction less than 3 months prior to screening visit Uncontrolled hypertension Active ocular infection or intraocular inflammation in any eye Treatment with any anti-angiogenic drugs within 3 months prior to baseline visit in any eye Active proliferative diabetic retinopathy in study eye Use of other investigational drugs within 30 days and systemic anti-VEGF drugs within 6 months prior to baseline visit Prior laser photocoagulation or intraocular procedure within 3 months prior to baseline in study eye History of intravitreal corticosteroid treatment in phakic study eye, and in aphakic or pseudophakic within 3 months prior to screening

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab (RFB002)<br>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser | Drug: Ranibizumab (RFB002)<br>* Ranibizumab 0.5 mg/0.05 mL for intravitreal injection<br>* Other names: Lucentis;Procedure: Sham laser<br>* Imitation of an active laser<br>|
| Active Comparator: Laser<br>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections | Procedure: Laser<br>* Laser photocoagulation according to Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines<br>Drug: Sham injection<br>* Imitation of an intravitreal injection consisting of an empty vial and an injection syringe without a needle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12 | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged [(Month1+Month2+...+Month12)/12], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Monthly from Month 1 through Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in BCVA (Letters) at Each Visit | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Monthly from Month 1 through Month 12 | 
| Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit | CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Monthly from Month 1 through Month 12 | 
| Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12 | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Month 12 | 
| Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12 | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Month 12 | 
| Percentage of Patients With BCVA ≥ 73 Letters at Month 12 | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis. | Month 12 | 
| Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3 | Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged [(Month4+Month5+...+Month12)/9],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis. | Monthly from Month 3 through Month 12 | 
| Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score | Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12 | General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12 | General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12 | Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12 | Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12 | Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12 | Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12 | Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12 | Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12 | Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12 | Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12 | Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening. | Baseline, Month 6, Month 12 | 
| Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12 | Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all. | Baseline, Month 6, Month 12 | 
| Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward | A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only. | Monthly from Month 3 through Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME, macular edema, vision impairment, Chinese, diabetes