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Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (RAVEN)

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ClinicalTrials.gov Identifier: NCT03810313
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : March 16, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 17, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date March 16, 2021
Actual Study Start Date  ICMJE July 3, 2019
Estimated Primary Completion Date November 3, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
Change from baseline in best-corrected visual acuity (BCVA) at Week 24 [ Time Frame: Baseline, Week 24 ]
Assessed with ETDRS visual acuity testing charts
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • Change from baseline in BCVA averaged over Week 40 to Week 52 and Week 64 to Week 76 [ Time Frame: Week 40 to Week 52, Week 64 to Week 76 ]
    Assessed with ETDRS visual acuity testing charts
  • Change from baseline in BCVA by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
    Assessed with ETDRS visual acuity testing charts
  • Proportion of study eyes with a gain ≥ 5, 10 and 15 letters in BCVA by visit compared to baseline [ Time Frame: Baseline to Week 76 ]
    Assessed with ETDRS visual acuity testing charts
  • Proportion of study eyes with a loss ≥ 5, 10 and 15 letters in BCVA by visit compared to baseline [ Time Frame: Baseline to Week 76 ]
    Assessed with ETDRS visual acuity testing charts
  • Change from baseline in central subfield thickness (CSFT) averaged over Week 40 to Week 52 and Week 64 to Week 76 [ Time Frame: Week 40 to Week 52 and Week 64 to Week 76 ]
    CSFT measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)
  • Change from baseline in CSFT by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
    CSFT measured in µm by SD-OCT
  • Proportion of study eyes with presence of retinal fluid (intra- and/or subretinal fluid) by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
    Presence of retinal fluid (intra- and/or subretinal fluid) assessed by SD-OCT
  • Proportion of study eyes with a CSFT < 300 µM by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
    CSFT measured in µm by SD-OCT
  • Number of injections between Week 24 and Week 52 and between Week 24 and Week 76 [ Time Frame: Week 24 to Week 52 and Week 24 to Week 76 ]
    Number of administered injections
  • Time to first re-treatment between Week 24 and Week 76 [ Time Frame: Week 24 to Week 76 ]
    Time to first injection after Week 24
  • Incidence of ocular and non-ocular AEs up to Week 52 and Week 76 [ Time Frame: Baseline to Week 76 ]
    Incidence of ocular and non-ocular AEs
  • Change from baseline in patient reported outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76 [ Time Frame: Baseline, Week 24, Week 52 and Week 76 ]
    The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains
  • Anti-drug antibody status at screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76 [ Time Frame: Screening, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76 ]
    Titration of ADA
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary The purpose of this study is 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 Following a 4-week maximum screening period, patients will be randomized and treated for approximately 76 weeks. Treatment visits will be scheduled in 4-week intervals. After 6 initial monthly injections of brolucizumab or aflibercept (loading phase), subjects will enter a one-year individualized flexible treatment (IFT) phase. During the IFT phase, an assessment of disease stability will be performed at each monthly visit and subjects will receive either an active or a sham injection. Treatment with active will be interrupted when disease stability is reached. Maximum study duration per patient is 80 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
A masked evaluating investigator will be responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator will perform the injections and assess patient safety following the injections.
Primary Purpose: Treatment
Condition  ICMJE Central Retinal Vein Occlusion
Intervention  ICMJE
  • Drug: Brolucizumab 6 mg
    Solution for injection (intravitreal use)
    Other Names:
    • RTH258
    • ESBA1008
  • Drug: Aflibercept 2 mg
    Solution for injection (Intravitreal use)
    Other Name: EYLEA®
  • Other: Sham injection
    Empty sterile syringe without a needle administered as a sham injection for masking
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: Brolucizumab 6 mg
    • Other: Sham injection
  • 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)
    Interventions:
    • Drug: Aflibercept 2 mg
    • Other: Sham injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2019)
750
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 3, 2023
Estimated Primary Completion Date November 3, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Canada,   China,   Czechia,   Finland,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Malaysia,   Netherlands,   Puerto Rico,   Russian Federation,   Spain,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03810313
Other Study ID Numbers  ICMJE CRTH258C2302
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP