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

Branch Retinal Vein Occlusion Clinical Trial

— RAPTOR  

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 Branch Retinal Vein Occlusion

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03802630
• Other study ID #: CRTH258C2301
• Secondary ID: 2018-001842-33
• Status: Terminated
• Phase: Phase 3
• Start date: July 2, 2019
• Est. completion date: July 26, 2021

Study information

• Verified date: January 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 branch retinal vein occlusion (BRVO).

Description:

The study was comprised of a 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 450
• Est. completion date: July 26, 2021
• Est. primary completion date: July 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Branch Retinal Vein Occlusion
• Macular Edema
• Retinal Vein Occlusion
• Vision Disorders
• Vision, Low

Intervention

Drug:
• Brolucizumab 6 mg
Solution for injection (intravitreal use)
• Aflibercept 2 mg
Solution for injection (Intravitreal use)

Other:
• Sham injection
Empty sterile syringe without a needle administered as a sham injection for masking purposes. 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.

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Graz
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Wenzhou	Zhejiang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuxi	Jiangsu
Czechia	Novartis Investigative Site	Pardubice
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Saint Cyr sur Loire	Indre Et Loire
France	Novartis Investigative Site	Strasbourg	Bas Rhin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Ulm
Hong Kong	Novartis Investigative Site	Hongkong
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Zerifin
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Amagasaki city	Hyogo
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Ishioka	Ibaraki
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Taito-ku	Tokyo
Puerto Rico	Novartis Investigative Site	Arecibo
Russian Federation	Novartis Investigative Site	Cheboksary
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Sterlitamak
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Zvolen
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sant Cugat	Catalunya
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Binningen
Switzerland	Novartis Investigative Site	Lausanne	Vaud
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Westcliff-on-Sea	Essex
United States	Novartis Investigative Site	Abilene	Texas
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Bellaire	Texas
United States	Novartis Investigative Site	Bloomfield	New Jersey
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Leawood	Kansas
United States	Novartis Investigative Site	Lenexa	Kansas
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Monroeville	Pennsylvania
United States	Novartis Investigative Site	Mountain View	California
United States	Novartis Investigative Site	New Albany	Indiana
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	Saint Petersburg	Florida
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Santa Barbara	California
United States	Novartis Investigative Site	Stoneham	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Puerto Rico,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24	BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.; Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.	Baseline, Week 24
Secondary	Change From Baseline in BCVA Averaged Over Week 40 to Week 52	An average BCVA over week 40 to week 52 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.	Baseline, Week 40 to Week 52
Secondary	Change From Baseline in BCVA Averaged Over Week 64 to Week 76	An average BCVA over week 64 to week 76 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.	Baseline, Week 64 to Week 76
Secondary	Change From Baseline in BCVA by Visit up to Week 76	BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.	Baseline and every 4 weeks from baseline up to Week 76
Secondary	Proportion of Participants With a Gain = 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline	The summary by visit was conducted based on the BCVA observed from each of the corresponding visits.; BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.; Every 5 letters represents 1 line of vision on the reading chart.	Baseline and every 4 weeks from baseline up to Week 76
Secondary	Proportion of Participants With a Loss = 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline	The summary by visit was conducted based on the BCVA observed from each of the corresponding visit.; BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.; Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.; Every 5 letters represents 1 line of vision on the reading chart.	Baseline and every 4 weeks from baseline up to Week 76
Secondary	Change From Baseline in CSFT Averaged Over Week 40 to Week 52	Change from baseline in central subfield thickness (CSFT) averaged over Week 40 to Week 52 , measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 40 to Week 52
Secondary	Change From Baseline in CSFT Averaged Over Week 64 to Week 76	Change from baseline in central subfield thickness (CSFT) averaged over Week 64 to Week 76, measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 64 to Week 76
Secondary	Change From Baseline in CSFT by Visit up to Week 76	Change from baseline in central subfield thickness (CSFT) measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, and every 4 weeks from baseline up to Week 76
Secondary	Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76	Presence of retinal fluid (intra- and/or subretinal fluid) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Every 4 weeks from baseline up to Week 76
Secondary	Proportion of Subjects With a CSFT < 300 µm for the Study Eye by Visit up to Week 76	Central subfield thickness (CSFT) is measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)	Every 4 weeks from Week 4 up to Week 76
Secondary	Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72	Number of administered injections during the individualized flexible treatment (IFT) period, between Week 24 and Week 52 and between Week 24 and Week 72 are presented	Week 24 to Week 52 and Week 24 to Week 72
Secondary	Time to Recurrence After Week 20 and up to Week 76	Recurrence is defined as the need for injection while showing a lack of disease stability for the first time after Week 20 and up to Week 76.; For subjects with recurrence after the Week 20 visit, time-to-event is calculated as (first time with the lack of disease stability - the injection date on Week 20 visit + 1). For subjects without recurrence after Week 20, the censoring time will be calculated as (last visit with disease stability assessment - the injection date on Week 20 visit + 1).	Week 20 to Week 76
Secondary	Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76	Number of subjects with at least one ocular or non-ocular Adverse Events (AEs).	Baseline to Week 76
Secondary	Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures a patient's subjective assessment of vision-related Quality of Life (QoL).; The 11 subscales in the VFQ-25 are general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated better vision-related quality of life.	Baseline, Week 24, Week 52 and Week 76
Secondary	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	Anti-drug antibodies (ADA) levels were assessed from subjects assigned to brolucizumab treatment only.	Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76

External Links

•   A Plain Language Trial Summary is available on novctrd.com
•   Results for CRTH258C2301 from the Novartis Clinical Trials Website