Clinical trial NCT01599650: Efficacy and Safety of Ranibizumab With or Without Laser in Comparison to Laser in Branch Retinal Vein Occlusion
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Branch Retinal Vein Occlusion
Keywords: Macular Edema, Branch Retinal Vein Occlusion, visual impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-16
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: Baseline, 6 Months
Secondary outcomes:
measure: The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline
timeFrame: Baseline, 24 Months
measure: Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group
timeFrame: Day 1 through Month 23
measure: Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6
timeFrame: From Baseline through Month 6
measure: The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24
timeFrame: Baseline, Month 12 and Month 24
measure: 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
timeFrame: Baseline, Month 6 and Month 24
measure: 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
timeFrame: Month 6
measure: 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
timeFrame: Month 24
measure: The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment Arm
timeFrame: Month 12 and Month 24
measure: 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
timeFrame: Months 6 and 24
measure: BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy Arm
timeFrame: Month 24
Other outcomes:
Locations:
city: Parramatta
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Victoria
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Boisbriand
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 10
country: Czech Republic
facility: Novartis Investigative Site
city: Glostrup
country: Denmark
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris Cedex 19
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
state: GR
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Dublin 7
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Bari
country: Italy
facility: Novartis Investigative Site
city: Udine
country: Italy
facility: Novartis Investigative Site
city: Leiden 2333 ZA
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Tilburg
country: Netherlands
facility: Novartis Investigative Site
city: Bielsko-Biala
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Kraków
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: L´Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bilbao
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Örebro
country: Sweden
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Olten
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Frimley
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Pawloff M, Bogunovic H, Gruber A, Michl M, Riedl S, Schmidt-Erfurth U. SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES. Retina. 2022 May 1;42(5):831-841. doi: 10.1097/IAE.0000000000003385.
citation: Tadayoni R, Waldstein SM, Boscia F, Gerding H, Gekkieva M, Barnes E, Das Gupta A, Wenzel A, Pearce I; BRIGHTER Study Group. Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study. Ophthalmology. 2017 Dec;124(12):1778-1787. doi: 10.1016/j.ophtha.2017.06.027. Epub 2017 Aug 12.
citation: Tadayoni R, Waldstein SM, Boscia F, Gerding H, Pearce I, Priglinger S, Wenzel A, Barnes E, Gekkieva M, Pilz S, Mones J; BRIGHTER study group. Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion: Six-Month Results of BRIGHTER. Ophthalmology. 2016 Jun;123(6):1332-44. doi: 10.1016/j.ophtha.2016.02.030. Epub 2016 Mar 30.