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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A 24-month, Phase IIIb, Open-label, Randomized, Active Controlled, 3-arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen Wit

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 Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: 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) [ Time Frame: Baseline, 6 Months ]

Original Primary Outcome: Mean change in visual acuity [ Time Frame: Baseline, 6 Months ]

Current Secondary Outcome:

• The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline [ Time Frame: Baseline, 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.
• Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group [ Time Frame: Day 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.
• Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6 [ Time Frame: From 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.
• The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24 [ Time Frame: Baseline, 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 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 Visit [ Time Frame: Baseline, 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 Eye [ Time Frame: Month 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.
• Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study Eye [ Time Frame: Month 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 Arm [ Time Frame: Month 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)
• The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to Baseline [ Time Frame: Months 6 and 24 ]
  The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activi
  
  

  Original Secondary Outcome:

  • The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline [ Time Frame: 24 months ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with best corrrected visual acuity (BCVA) letter gain or loss from Baseline will be 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)
  • The number of ranibizumab treatments [ Time Frame: Month 1 through Month 24 ]
    Will be conducted within the FAS with LOCF and observed data .
  • Mean average change in visual acuity from Month 1 through Month 6 [ Time Frame: From Baseline through Month 6 ]
    Assessed by an ANOVA model. Endpoints related to the proportion of patients with best corrected visual acuity (BCVA) letter gain or loss from Baseline will be 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).
  • The mean change in visual acuity from Baseline up to Month 12 and Month 24 [ Time Frame: From Baseline through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with best corrected visual acuity (BCVA) letter gain or loss from Baseline will be analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59 letters, greater than or equal to 60 letters, treatment groups)
  • The mean average change in visual acuity from the time point of the first treatment interruption (due to visual acuity stabilization) for all following visits until End of Study [ Time Frame: First treatment interruption through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with best corrected visual acuity (BCVA) letters gained or lost.
  • The mean change in visual acuity from the time point of the first treatment interruption (due to BCVA stabilization) assessed on a monthly basis until End of Study [ Time Frame: First treatment interruption through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letters gained or lost.
  • The proportion of patients with a visual acuity gain of ≥1, ≥5, ≥10, ≥15, and ≥30 letters / loss of <15 letters from Baseline up to Month 6 and Month 24, by visit [ Time Frame: Baseline through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline will be 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).
  • The proportion of patients with a visual acuity value ≥73 letters (20/40 Snellen equivalent) from Baseline up to Month 6 and Month 24, by visit [ Time Frame: Baseline through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline will be 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).
  • The mean average visual acuity change from the time point of first ranibizumab treatment for all following visits until End of Study in patients randomized to laser [ Time Frame: First treatment through Month 24 ]
    Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gained or lost.
  • The mean change in reading center assessed central subfoveal thickness from Baseline up to Month 6 and Month 24, by visit [ Time Frame: Baseline through Month 24 ]
    will be based on an analysis of variance (ANOVA). Stratification will be done based on categories of baseline best corrected visual acuity
  • The mean change in patient reported outcomes in NEI-VFQ-25 score (composite score and subscales) at Month 6 and Month 24 compared to Baseline [ Time Frame: Baseline through Month 24 ]
    The statistical hypothesis testing of the mean change from Baseline in BCVA will be based on an analysis of variance (ANOVA). Stratification will be done based on categories of baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, and greater than or equal to 60 letters).

  
  
  Information By: Novartis
  

  Dates:
  Date Received: May 2, 2012
  Date Started: May 2012
  Date Completion:
  Last Updated: September 21, 2016
  Last Verified: September 2016
  

  

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