The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03810313




Registration number
NCT03810313
Ethics application status
Date submitted
17/01/2019
Date registered
18/01/2019

Titles & IDs
Public title
Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
Scientific 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
Secondary ID [1] 0 0
2018-001788-21
Secondary ID [2] 0 0
CRTH258C2302
Universal Trial Number (UTN)
Trial acronym
RAVEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Central Retinal Vein Occlusion 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Brolucizumab 6 mg
Treatment: Drugs - Aflibercept 2 mg
Other interventions - Sham injection

Experimental: Brolucizumab 6 mg - 1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)

Active comparator: Aflibercept 2 mg - 1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)


Treatment: Drugs: Brolucizumab 6 mg
Solution for injection (intravitreal use)

Treatment: Drugs: Aflibercept 2 mg
Solution for injection (Intravitreal use)

Other interventions: Sham injection
Empty sterile syringe without a needle administered as a sham injection for masking. From Week 24 to Week 72 inclusive, a sham treatment was performed to maintain subject masking in case treatment with brolucizumab or aflibercept was not deemed necessary by the investigator.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change From Baseline in BCVA Averaged Over Week 40 to Week 52
Timepoint [1] 0 0
Baseline, Week 40 to Week 52
Secondary outcome [2] 0 0
Change From Baseline in BCVA Averaged Over Week 64 to Week 76
Timepoint [2] 0 0
Baseline, Week 64 to Week 76
Secondary outcome [3] 0 0
Change From Baseline in BCVA by Visit up to Week 76
Timepoint [3] 0 0
Baseline and every 4 weeks from baseline up to Week 76
Secondary outcome [4] 0 0
Proportion of Participants With a Gain = 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
Timepoint [4] 0 0
Baseline and every 4 weeks from baseline up to Week 76
Secondary outcome [5] 0 0
Proportion of Participants With a Loss = 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
Timepoint [5] 0 0
Baseline and every 4 weeks from baseline up to Week 76
Secondary outcome [6] 0 0
Change From Baseline in CSFT Averaged Over Week 40 to Week 52
Timepoint [6] 0 0
Baseline, Week 40 to Week 52
Secondary outcome [7] 0 0
Change From Baseline in CSFT Averaged Over Week 64 to Week 76
Timepoint [7] 0 0
Baseline, Week 64 to Week 76
Secondary outcome [8] 0 0
Change From Baseline in CSFT by Visit up to Week 76
Timepoint [8] 0 0
Baseline, and every 4 weeks from baseline up to Week 76
Secondary outcome [9] 0 0
Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76
Timepoint [9] 0 0
Every 4 weeks from week 4 up to Week 76
Secondary outcome [10] 0 0
Proportion of Subjects With a CSFT < 300 µm for the Study Eye by Visit up to Week 76
Timepoint [10] 0 0
Every 4 weeks from week 4 up to Week 76
Secondary outcome [11] 0 0
Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72
Timepoint [11] 0 0
Week 24 to Week 52 and Week 24 to Week 72
Secondary outcome [12] 0 0
Time to Recurrence After Week 20 and up to Week 76
Timepoint [12] 0 0
Week 20 to Week 76
Secondary outcome [13] 0 0
Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76
Timepoint [13] 0 0
Baseline to Week 76
Secondary outcome [14] 0 0
Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76
Timepoint [14] 0 0
Baseline, Week 24, Week 52 and Week 76
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Albury
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parramatta
Recruitment hospital [3] 0 0
Novartis Investigative Site - Strathfield
Recruitment hospital [4] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [5] 0 0
Novartis Investigative Site - Hobart
Recruitment hospital [6] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [7] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2150 - Parramatta
Recruitment postcode(s) [3] 0 0
2135 - Strathfield
Recruitment postcode(s) [4] 0 0
2000 - Sydney
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3002 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Guangdong
Country [21] 0 0
China
State/province [21] 0 0
Heilongjiang
Country [22] 0 0
China
State/province [22] 0 0
Hubei
Country [23] 0 0
China
State/province [23] 0 0
Jiangsu
Country [24] 0 0
China
State/province [24] 0 0
Sichuan
Country [25] 0 0
China
State/province [25] 0 0
Tianjin
Country [26] 0 0
China
State/province [26] 0 0
Zhejiang
Country [27] 0 0
China
State/province [27] 0 0
Beijing
Country [28] 0 0
China
State/province [28] 0 0
Chongqing
Country [29] 0 0
China
State/province [29] 0 0
Shanghai
Country [30] 0 0
Czechia
State/province [30] 0 0
CZE
Country [31] 0 0
Czechia
State/province [31] 0 0
Pardubice
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha 10
Country [33] 0 0
Czechia
State/province [33] 0 0
Praha
Country [34] 0 0
France
State/province [34] 0 0
Creteil
Country [35] 0 0
France
State/province [35] 0 0
Dijon
Country [36] 0 0
France
State/province [36] 0 0
Nantes
Country [37] 0 0
France
State/province [37] 0 0
Paris cedex 10
Country [38] 0 0
France
State/province [38] 0 0
Paris Cedex 19
Country [39] 0 0
Germany
State/province [39] 0 0
Bavaria
Country [40] 0 0
Germany
State/province [40] 0 0
Duesseldorf
Country [41] 0 0
Germany
State/province [41] 0 0
Freiburg
Country [42] 0 0
Germany
State/province [42] 0 0
Gottingen
Country [43] 0 0
Germany
State/province [43] 0 0
Hannover
Country [44] 0 0
Germany
State/province [44] 0 0
Heidelberg
Country [45] 0 0
Germany
State/province [45] 0 0
Leipzig
Country [46] 0 0
Germany
State/province [46] 0 0
Mainz
Country [47] 0 0
Germany
State/province [47] 0 0
Muenster
Country [48] 0 0
Germany
State/province [48] 0 0
Ulm
Country [49] 0 0
Greece
State/province [49] 0 0
GR
Country [50] 0 0
Greece
State/province [50] 0 0
Heraklion Crete
Country [51] 0 0
Hungary
State/province [51] 0 0
Baranya
Country [52] 0 0
Hungary
State/province [52] 0 0
Budapest
Country [53] 0 0
Hungary
State/province [53] 0 0
Debrecen
Country [54] 0 0
Hungary
State/province [54] 0 0
Szeged
Country [55] 0 0
Israel
State/province [55] 0 0
Jerusalem
Country [56] 0 0
Israel
State/province [56] 0 0
Petach Tikva
Country [57] 0 0
Israel
State/province [57] 0 0
Rehovot
Country [58] 0 0
Israel
State/province [58] 0 0
Tel Aviv
Country [59] 0 0
Italy
State/province [59] 0 0
BA
Country [60] 0 0
Italy
State/province [60] 0 0
MI
Country [61] 0 0
Japan
State/province [61] 0 0
Aichi
Country [62] 0 0
Japan
State/province [62] 0 0
Fukushima
Country [63] 0 0
Japan
State/province [63] 0 0
Kagawa
Country [64] 0 0
Japan
State/province [64] 0 0
Mie
Country [65] 0 0
Japan
State/province [65] 0 0
Nagano
Country [66] 0 0
Japan
State/province [66] 0 0
Nagasaki
Country [67] 0 0
Japan
State/province [67] 0 0
Tokyo
Country [68] 0 0
Malaysia
State/province [68] 0 0
Selangor
Country [69] 0 0
Netherlands
State/province [69] 0 0
Tilburg
Country [70] 0 0
Puerto Rico
State/province [70] 0 0
Arecibo
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Cheboksary
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Ekaterinburg
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Kazan
Country [74] 0 0
Russian Federation
State/province [74] 0 0
St-Petersburg
Country [75] 0 0
Spain
State/province [75] 0 0
Pais Vasco
Country [76] 0 0
Spain
State/province [76] 0 0
Barcelona
Country [77] 0 0
Spain
State/province [77] 0 0
Madrid
Country [78] 0 0
Spain
State/province [78] 0 0
Valencia
Country [79] 0 0
Spain
State/province [79] 0 0
Zaragoza
Country [80] 0 0
Thailand
State/province [80] 0 0
Hat Yai
Country [81] 0 0
Thailand
State/province [81] 0 0
THA
Country [82] 0 0
Thailand
State/province [82] 0 0
Bangkok
Country [83] 0 0
Turkey
State/province [83] 0 0
Ankara
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Suffolk
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Leeds
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Liverpool
Country [87] 0 0
United Kingdom
State/province [87] 0 0
London
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.