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

Branch Retinal Vein Occlusion Clinical Trial

— BRIGHTER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01599650
• Other study ID #: CRFB002E2402
• Secondary ID: 2011-002859-34
• Status: Completed
• Phase: Phase 3
• First received: May 2, 2012
• Last updated: October 6, 2015
• Start date: May 2012
• Est. completion date: May 2015

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research CouncilAustria: Agency for Health and Food SafetyCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: National Board of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesHungary: National Institute of PharmacyIreland: Irish Medicines BoardItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteSlovakia: State Institute for Drug ControlSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicSweden: The National Board of Health and WelfareTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Branch Retinal Vein Occlusion
• Retinal Vein Occlusion

Intervention

Drug:
• Ranibizumab

Procedure:
• Laser
laser photocoagulation

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Sydney	New South Wales
Canada	Novartis Investigative Site	Boisbriand	Quebec
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoria	British Columbia
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Praha 10
Denmark	Novartis Investigative Site	Glostrup
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Paris Cedex 19
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Heraklion Crete	GR
Greece	Novartis Investigative Site	Larissa	GR
Greece	Novartis Investigative Site	Patras
Greece	Novartis Investigative Site	Thessaloniki
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin 7
Italy	Novartis Investigative Site	Bari
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Udine
Netherlands	Novartis Investigative Site	Leiden 2333 ZA
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Tilburg
Poland	Novartis Investigative Site	Bielsko-Biala
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Kraków
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Zilina	Slovak Republic
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	L´Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Sweden	Novartis Investigative Site	Örebro
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Olten
Switzerland	Novartis Investigative Site	Zuerich
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Canada,  Czech Republic,  Denmark,  France,  Greece,  Hungary,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in visual acuity	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	Baseline, 6 months	No
Secondary	The mean average change in visual acuity from Month 1 through Month 24 compared to Baseline	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)	24 months	No
Secondary	The number of ranibizumab treatments	Will be conducted within the FAS with LOCF and observed data .	Month 1 through Month 24	No
Secondary	Mean average change in visual acuity from Month 1 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).	From Baseline through Month 6	No
Secondary	The mean change in visual acuity from Baseline up to Month 12 and 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)	From Baseline through Month 24	No
Secondary	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	Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with best corrected visual acuity (BCVA) letters gained or lost.	First treatment interruption through Month 24	No
Secondary	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	Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letters gained or lost.	First treatment interruption through Month 24	No
Secondary	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	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).	Baseline through Month 24	No
Secondary	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	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).	Baseline through Month 24	No
Secondary	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	Will be assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gained or lost.	First treatment through Month 24	No
Secondary	The mean change in reading center assessed central subfoveal thickness from Baseline up to Month 6 and Month 24, by visit	will be based on an analysis of variance (ANOVA). Stratification will be done based on categories of baseline best corrected visual acuity	Baseline through Month 24	No
Secondary	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	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).	Baseline through Month 24	No