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Efficacy and Safety of Ranibizumab With or Without Laser in Comparison to Laser in Branch Retinal Vein Occlusion

Phase 3
Completed
Conditions
Branch Retinal Vein Occlusion
Interventions
Procedure: Laser
Registration Number
NCT01599650
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study will generate comparative data for 0.5-mg ranibizumab using PRN dosing administered with or without adjunctive laser treatment versus laser photocoagulation (the current standard of care) up to Month 6 in patients with visual impairment due to ME secondary to BRVO. Additionally the results of this study will provide long-term (24-month) safety and efficacy data for ranibizumab, administered with or without adjunctive laser treatment in this indication.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
455
Inclusion Criteria
  • Written informed consent must be obtained before any study assessment is performed
  • Diagnosis of visual impairment exclusively due to ME secondary to BRVO
  • BCVA score at Screening and Baseline between 73 and 19 letters (ETDRS)
Exclusion Criteria
  • Pregnant or nursing (lactating) women
  • Stroke or myocardial infarction less than 3 months before Screening
  • Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at Screening or Baseline.
  • Any active periocular or ocular infection or inflammation at Screening or Baseline in either eye
  • Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before Baseline in either eye
  • Neovascularization of the iris or neovascular glaucoma in the study eye
  • Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline
  • Panretinal laser photocoagulation within 3 months before Baseline or anticipated or scheduled within the next 3 months following Baseline in the study eye
  • Focal or grid laser photocoagulation within 4 months before Baseline in the study eye
  • Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months before Screening in the study eye
  • Any use of intraocular corticosteroid implants (eg, dexamethasone [Ozurdex®], fluocinolone acetonide [Iluvien®]) in the study eye

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
3-laser monotherapyLaserLaser monotherapy with Ranibizumab 0.5 mg from Month 6
2-ranibizumab with laserLaserRanibizumab 0.5 mg + laser
1-ranibizumab monotherapyRanibizumabRanibizumab 0.5 mg
2-ranibizumab with laserRanibizumabRanibizumab 0.5 mg + laser
Primary Outcome Measures
NameTimeMethod
Mean Change in Visual Acuity: BCVA Change at Month 6 Compared to Baseline in Patients With Visual Impairment Due to Branch Retinal Vein Occlusion (BRVO)Baseline, 6 Months

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)

-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 6 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

Secondary Outcome Measures
NameTimeMethod
Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6From Baseline through Month 6

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters.(A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 6. Then, mean average change is calculated as the average of average changes across all patients.

Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment GroupDay 1 through Month 23

Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.

The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to BaselineBaseline, 24 Months

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. (A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 24. Then, mean average change is calculated as the average of average changes across all patients.

The Percent of Patients With a Visual Acuity Gain of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline up to Month 6 and Month 24, by VisitBaseline, Month 6 and Month 24

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 6 \& Month 24 as compared with baseline, was assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline was analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, greater than or equal to 60 letters, treatment groups).

Number of Patients With a BCVA Improvement vs Baseline or Achieving Greater Than or Equal to 73 Letters at Month 6 in the Study EyeMonth 6

Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 6 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 6 indicates a positive outcome.

The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24Baseline, Month 12 and Month 24

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and were assessed by an ANOVA model.

The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to BaselineMonths 6 and 24

The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.

BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy ArmMonth 24

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)

-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study EyeMonth 24

Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 24 indicates a positive outcome.

The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment ArmMonth 12 and Month 24

Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation. Stratification was done based on categories of baseline best corrected visual acuity \& analysis was based on analysis of variance (ANOVA)

Trial Locations

Locations (1)

Novartis Investigative Site

🇬🇧

Southampton, United Kingdom

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