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)

• ClinicalTrials.gov Identifier: NCT03810313
• Recruitment Status: Recruiting
• First Posted: January 18, 2019
• Last Update Posted: September 26, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Central Retinal Vein Occlusion	Drug: Brolucizumab 6 mg; Drug: Aflibercept 2 mg; Other: Sham injection	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 750 participants
• 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
• 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
• Actual Study Start Date: July 3, 2019
• Estimated Primary Completion Date: January 12, 2023
• Estimated Study Completion Date: February 10, 2023

Arms and Interventions

Arm	Intervention/treatment
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)	Drug: Brolucizumab 6 mg; Solution for injection (intravitreal use); Other Names: RTH258; ESBA1008; Other: Sham injection; Empty sterile syringe without a needle administered as a sham injection for masking
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)	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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in best-corrected visual acuity (BCVA) at Week 24 [ Time Frame: Baseline, Week 24 ]
   Assessed with ETDRS visual acuity testing charts

Secondary Outcome Measures :

1. 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
2. Change from baseline in BCVA by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
   Assessed with ETDRS visual acuity testing charts
3. 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
4. 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
5. 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)
6. Change from baseline in CSFT by visit up to Week 76 [ Time Frame: Baseline to Week 76 ]
   CSFT measured in µm by SD-OCT
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.
• Patients with visual impairment due to ME secondary to BRVO 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 BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded.
• 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

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

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Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03810313 History of Changes
• Other Study ID Numbers: CRTH258C2302
• First Posted: January 18, 2019
• Last Update Posted: September 26, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Visual impairment; Macular edema; Central retinal vein occlusion; CRVO; Brolucizumab; Aflibercept; Vascular endothelial growth factor; VEGF; anti-VEGF

Additional relevant MeSH terms:

Vision Disorders; Vision, Low; Macular Edema; Retinal Vein Occlusion; Signs and Symptoms; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases