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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03810313
Other study ID # CRTH258C2302
Secondary ID 2018-001788-21
Status Terminated
Phase Phase 3
First received
Last updated
Start date July 3, 2019
Est. completion date July 26, 2021

Study information

Verified date January 2023
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
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 central retinal vein occlusion (CRVO).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 493
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 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

Study Design


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. 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
Australia Novartis Investigative Site Albury New South Wales
Australia Novartis Investigative Site Hobart Tasmania
Australia Novartis Investigative Site Melbourne Victoria
Australia Novartis Investigative Site Nedlands Western Australia
Australia Novartis Investigative Site Parramatta New South Wales
Australia Novartis Investigative Site Strathfield New South Wales
Australia Novartis Investigative Site Sydney New South Wales
Canada Novartis Investigative Site Calgary Alberta
Canada Novartis Investigative Site London Ontario
Canada Novartis Investigative Site Ottawa Ontario
Canada Novartis Investigative Site Ottawa Ontario
Canada Novartis Investigative Site Quebec
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 Harbin Heilongjiang
China Novartis Investigative Site Shanghai
China Novartis Investigative Site Shantou Guangdong
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 Hradec Kralove CZE
Czechia Novartis Investigative Site Pardubice
Czechia Novartis Investigative Site Praha
Czechia Novartis Investigative Site Praha 10
France Novartis Investigative Site Creteil
France Novartis Investigative Site Dijon
France Novartis Investigative Site Nantes
France Novartis Investigative Site Paris cedex 10
France Novartis Investigative Site Paris Cedex 19
Germany Novartis Investigative Site Duesseldorf
Germany Novartis Investigative Site Freiburg
Germany Novartis Investigative Site Gottingen
Germany Novartis Investigative Site Hannover
Germany Novartis Investigative Site Heidelberg
Germany Novartis Investigative Site Leipzig
Germany Novartis Investigative Site Mainz
Germany Novartis Investigative Site Muenster
Germany Novartis Investigative Site Regensburg Bavaria
Germany Novartis Investigative Site Ulm
Greece Novartis Investigative Site Heraklion Crete
Greece Novartis Investigative Site Larissa GR
Hungary Novartis Investigative Site Budapest
Hungary Novartis Investigative Site Debrecen
Hungary Novartis Investigative Site Pecs Baranya
Hungary Novartis Investigative Site Szeged
Israel Novartis Investigative Site Jerusalem
Israel Novartis Investigative Site Petach Tikva
Israel Novartis Investigative Site Rehovot
Israel Novartis Investigative Site Tel Aviv
Italy Novartis Investigative Site Bari BA
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Milano MI
Japan Novartis Investigative Site Chiyoda-ku Tokyo
Japan Novartis Investigative Site Hachioji-city Tokyo
Japan Novartis Investigative Site Kita-gun Kagawa
Japan Novartis Investigative Site Koriyama Fukushima
Japan Novartis Investigative Site Matsumoto-city Nagano
Japan Novartis Investigative Site Nagakute-city Aichi
Japan Novartis Investigative Site Nagasaki-city Nagasaki
Japan Novartis Investigative Site Taito-ku Tokyo
Japan Novartis Investigative Site Tsu-city Mie
Malaysia Novartis Investigative Site Batu Caves Selangor
Malaysia Novartis Investigative Site Shah Alam Selangor
Netherlands Novartis Investigative Site Tilburg
Puerto Rico Novartis Investigative Site Arecibo
Russian Federation Novartis Investigative Site Cheboksary
Russian Federation Novartis Investigative Site Ekaterinburg
Russian Federation Novartis Investigative Site Kazan
Russian Federation Novartis Investigative Site St-Petersburg
Spain Novartis Investigative Site Barcelona
Spain Novartis Investigative Site Barcelona
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site San Sebastian Pais Vasco
Spain Novartis Investigative Site Valencia
Spain Novartis Investigative Site Zaragoza
Thailand Novartis Investigative Site Bangkok
Thailand Novartis Investigative Site Khon Kaen THA
Thailand Novartis Investigative Site Songkhla Hat Yai
Turkey Novartis Investigative Site Ankara
United Kingdom Novartis Investigative Site Bury Saint Edmonds Suffolk
United Kingdom Novartis Investigative Site Leeds
United Kingdom Novartis Investigative Site Liverpool
United Kingdom Novartis Investigative Site London
United Kingdom Novartis Investigative Site Newcastle Upon Tyne
United States Novartis Investigative Site Abilene Texas
United States Novartis Investigative Site Arlington Texas
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 Cleveland Ohio
United States Novartis Investigative Site Colorado Springs Colorado
United States Novartis Investigative Site Fort Myers Florida
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 La Jolla California
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 Memphis Tennessee
United States Novartis Investigative Site Minneapolis Minnesota
United States Novartis Investigative Site Monroeville Pennsylvania
United States Novartis Investigative Site Mountain View California
United States Novartis Investigative Site Nashville Tennessee
United States Novartis Investigative Site New Albany Indiana
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,  Australia,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Malaysia,  Netherlands,  Puerto Rico,  Russian Federation,  Spain,  Thailand,  Turkey,  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 week 4 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
See also
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