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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01599650
First received: May 2, 2012
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Branch Retinal Vein Occlusion
Drug: Ranibizumab
Procedure: Laser
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy or With Adjunctive Laser Photocoagulation in Comparison to Laser Photocoagulation in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Mean change in visual acuity [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    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 will be calculated


Secondary Outcome Measures:
  • The mean average change in visual acuity from Month 1 through Month 24 compared to Baseline [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 454
Study Start Date: May 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1-ranibizumab monotherapy Drug: Ranibizumab
Other Name: Lucentis
Experimental: 2-ranibizumab with laser Drug: Ranibizumab
Other Name: Lucentis
Procedure: Laser
laser photocoagulation
Other Name: laser
Active Comparator: 3-laser monotherapy Procedure: Laser
laser photocoagulation
Other Name: laser

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01599650

  Show 82 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01599650     History of Changes
Other Study ID Numbers: CRFB002E2402, 2011-002859-34
Study First Received: May 2, 2012
Last Updated: June 5, 2014
Health Authority: Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: National Board of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Sweden: The National Board of Health and Welfare
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Macular Edema, Branch Retinal Vein Occlusion, visual impairment

Additional relevant MeSH terms:
Retinal Vein Occlusion
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 19, 2014