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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01599650
First received: May 2, 2012
Last updated: September 21, 2016
Last verified: September 2016
  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: 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 ] [ Designated as safety issue: No ]

    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:
  • The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline [ Time Frame: Baseline, 24 Months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Arm [ Time Frame: Month 24 ] [ Designated as safety issue: No ]

    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.



Enrollment: 455
Study Start Date: May 2012
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1-ranibizumab monotherapy
Ranibizumab 0.5 mg
Drug: Ranibizumab
Other Name: Lucentis
Experimental: 2-ranibizumab with laser
Ranibizumab 0.5 mg + laser
Drug: Ranibizumab
Other Name: Lucentis
Procedure: Laser
laser photocoagulation
Active Comparator: 3-laser monotherapy
Laser monotherapy with Ranibizumab 0.5 mg from Month 6
Procedure: Laser
laser photocoagulation

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01599650     History of Changes
Other Study ID Numbers: CRFB002E2402  2011-002859-34 
Study First Received: May 2, 2012
Results First Received: May 26, 2016
Last Updated: September 21, 2016
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
Vision Disorders
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Ranibizumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016