Clinical trial NCT03810313: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
Official title: An Eighteen-Month, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Central Retinal Vein Occlusion
Keywords: Visual impairment
Macular edema
Central retinal vein occlusion
CRVO
Brolucizumab
Aflibercept
Vascular endothelial growth factor
VEGF
anti-VEGF
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-01-18
Enrollment: 493
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: The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Detailed description: The study included Screening Period (Day -28 to Day -1), double-masked treatment period (Day 1 to Week 72), and post-treatment follow-up period (Week 72 to Week 76). Treatment visits were scheduled in 4-week intervals. After 6 initial monthly injections of brolucizumab or aflibercept (loading phase), subjects entered a one-year individualized flexible treatment (IFT) phase. During the IFT phase, an assessment of disease stability was performed at each monthly visit and subjects received either an active or a sham injection. Treatment with active was interrupted when disease stability was reached.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Patients with visual impairment due to ME secondary to CRVO diagnosed \< 6 months prior to screening.
* BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.

Exclusion criteria

* Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema).
* Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
* Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) \> 25 mmHg on medication, or according to investigator's judgment, at screening or baseline
* Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA \< 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
* Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline
* Previous use of intraocular or periocular steroids in study eye at any time prior to baseline
* Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline
* Intraocular surgery in the study eye during the 3-month period prior to baseline
* Vitreoretinal surgery in the study eye at any time prior to baseline
* Aphakia with the absence of posterior capsule in the study eye

Primary outcomes:
measure: Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in BCVA Averaged Over Week 40 to Week 52
timeFrame: Baseline, Week 40 to Week 52
measure: Change From Baseline in BCVA Averaged Over Week 64 to Week 76
timeFrame: Baseline, Week 64 to Week 76
measure: Change From Baseline in BCVA by Visit up to Week 76
timeFrame: Baseline and every 4 weeks from baseline up to Week 76
measure: Proportion of Participants With a Gain ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
timeFrame: Baseline and every 4 weeks from baseline up to Week 76
measure: Proportion of Participants With a Loss ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
timeFrame: Baseline and every 4 weeks from baseline up to Week 76
measure: Change From Baseline in CSFT Averaged Over Week 40 to Week 52
timeFrame: Baseline, Week 40 to Week 52
measure: Change From Baseline in CSFT Averaged Over Week 64 to Week 76
timeFrame: Baseline, Week 64 to Week 76
measure: Change From Baseline in CSFT by Visit up to Week 76
timeFrame: Baseline, and every 4 weeks from baseline up to Week 76
measure: Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76
timeFrame: Every 4 weeks from week 4 up to Week 76
measure: Proportion of Subjects With a CSFT < 300 μm for the Study Eye by Visit up to Week 76
timeFrame: Every 4 weeks from week 4 up to Week 76
measure: Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72
timeFrame: Week 24 to Week 52 and Week 24 to Week 72
measure: Time to Recurrence After Week 20 and up to Week 76
timeFrame: Week 20 to Week 76
measure: Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76
timeFrame: Baseline to Week 76
measure: Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76
timeFrame: Baseline, Week 24, Week 52 and Week 76
measure: Number of Subjects According to Their Anti-drug Antibody (ADA) Titer at Screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: La Jolla
country: United States
facility: Novartis Investigative Site
state: California
city: Mountain View
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Barbara
country: United States
facility: Novartis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Saint Petersburg
country: United States
facility: Novartis Investigative Site
state: Florida
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: New Albany
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Leawood
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Lenexa
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Stoneham
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Reno
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Bloomfield
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Monroeville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Abilene
country: United States
facility: Novartis Investigative Site
state: Texas
city: Arlington
country: United States
facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bellaire
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Albury
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Parramatta
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Strathfield
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Hobart
country: Australia
facility: Novartis Investigative Site
state: Tasmania
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: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shantou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Wuxi
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Pardubice
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Nantes
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: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
state: Baranya
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Koriyama
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Matsumoto-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Nagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Chiyoda-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hachioji-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Taito-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Batu Caves
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Shah Alam
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Tilburg
country: Netherlands
facility: Novartis Investigative Site
city: Arecibo
country: Puerto Rico
facility: Novartis Investigative Site
city: Cheboksary
country: Russian Federation
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: St-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Bury Saint Edmonds
country: United Kingdom
facility: Novartis Investigative Site
state: Suffolk
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
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
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: