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

Phase 3

Completed

Conditions: Diabetic Macular Edema
Visual Impairment

Interventions: Drug: Ranibizumab (RFB002)
Procedure: Laser
Procedure: Sham laser
Drug: Sham injection

Registration Number: NCT02259088

Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 384

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ranibizumab (RFB002)	Ranibizumab (RFB002)	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
Laser	Laser	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
Ranibizumab (RFB002)	Sham laser	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
Laser	Sham injection	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

Primary Outcome Measures

Name	Time	Method
Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12	Baseline, Monthly from Month 1 through 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. 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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in BCVA (Letters) at Each Visit	Baseline, Monthly from Month 1 through 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.
Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12	Baseline, 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.
Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12	Baseline, 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.
Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Baseline, Monthly from Month 1 through Month 12	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.
Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Monthly from Month 3 through 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. 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.
Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score	Baseline, Month 6, Month 12	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.
Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12	Baseline, Month 6, 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.
Percentage of Patients With BCVA ≥ 73 Letters at Month 12	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.
Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12	Baseline, Month 6, 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.
Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward	Monthly from Month 3 through Month 12	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.
Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12	Baseline, Month 6, 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.