Comparing Intravitreal Brolucizumab Monotherapy vs Aflibercept Monotherapy in PCV Treatment

A Multi-centre Double-blind Randomized Clinical Trial Comparing Intravitreal Brolucizumab Monotherapy vs Aflibercept Monotherapy in the Treatment of Polypoidal Choroidal Vasculopathy

Sponsoren

Hauptsponsor: Singapore National Eye Centre

Mitarbeiter: National University Hospital, Singapore
Tan Tock Seng Hospital

Quelle Singapore National Eye Centre
Kurze Zusammenfassung

In this study, we aim to compare the efficacy and safety of a practical individualized pro re nata treatment regimen between Brolucizamab and Aflibercept in patients with polypoidal choroidal vasculopathy (PCV).

detaillierte Beschreibung

Age related macular degeneration (AMD) is one of the leading causes of blindness worldwide. In its exudative or wet form, choroidal neovascularization (CNV) causes an exudative maculopathy resulting in sudden loss of vision with severe effects on patients' quality of life. Intravitreal injections of anti-vascular endothelial growth factor agents (anti-VEGF) have become the mainstay of treatment for AMD CNV and has been shown to have favourable outcomes in most AMD CNV subtypes. In the Asian population, however, a particular subtype called polypoidal choroidal vasculopathy (PCV), which affects about 50% of exudative maculopathy, has been shown to have less favourable response to anti-VEGF therapy.

The best treatment option for PCV has remained unclear. Having favorable visual outcomes, anti-VEGF monotherapy has superseded photodynamic therapy as an effective first line of treatment for PCV.3,4 The non-inferiority of intravitreal (IVT) Aflibercept monotherapy vs combined therapy in terms of mean change in visual acuity from baseline to 1 year was well described in a pivotal randomized control trial, the PLANET study in 2018.5 In the recent released results of the Hawk and Harrier Study (2019), Brolucizumab, a novel anti-VEGF therapy, showed non-inferior clinical results compared to Aflibercept therapy in patients with neovascularAMD. In this study, a 3 monthly loading dose was given and a treat and extend protocol was followed. Visual function was found to be comparable between treatment arms while, anatomical outcomes were significantly better with Brolucizumab.

Though anti-VEGF therapy has improved visual outcomes in the treatment of PCV, frequent clinic visits, injection visits as well as cost has remained to be a burdensome unmet need for patients diagnosed with PCV. A need for a more sustainable and cost-effective treatment regimen should therefore be studied to provide a practical solution for this unmet need. A multi-centred randomised controlled trial would give the best evidence in comparing the 2 treatment modalities.

Gesamtstatus Not yet recruiting
Anfangsdatum October 1, 2020
Fertigstellungstermin December 30, 2022
Primäres Abschlussdatum November 30, 2020
Phase N/A
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Visual Acuity change 12 months
Sekundäres Ergebnis
Messen Zeitfenster
Optical Coherence Tomography 12 months
Optical Coherence Tomography-Angiograph 12 months
Color fundus photography baseline, month 3, month12
Autofluorescence Photography baseline, month 3, month12
Einschreibung 160
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: Aflibercept

Beschreibung: Aflibercept dosage of 2mg in 0.05ml

Armgruppenetikett: Aflibercept Monotherapy

Anderer Name: Eylea

Interventionsart: Drug

Interventionsname: Brolucizumab

Beschreibung: Brolucizumab dosage of 6mg in 0.05ml

Armgruppenetikett: Brolucizumab Monotherapy

Teilnahmeberechtigung

Kriterien:

Inclusion Criteria:

- Patients aged over 50 years old at the time of informed consent.

- Provide written informed consent.

- Willingness and ability to comply with all scheduled visits and study procedures.

- Confirmed diagnosis of symptomatic macular PCV based ICGA.

- Activity of PCV confirmed by exudative activity involving the macula on OCT or Fluorescein Angiography (FA) or both.

- Presence of intra retinal or subretinal fluid/blood at the fovea as seen on OCT

- Treatment naïve

- NO previous treatment with intravitreal anti-VEGF agents, regardless of the indication

- NO previous thermal laser in the macular region, or verteporfin photodynamic therapy (vPDT), regardless of indication

- NO other previous treatment for neovascular AMD (nAMD), except oral supplements and traditional Chinese medicine

- An ETDRS BCVA of 4 to 73 letters (Snellen equivalent approximately 20/32 to 20/800) in the study eye.

- Greatest Linear Dimension (GLD) of the total lesion area (BVN + polyps < 5400µm (~9 mucopolysaccharidoses (MPS) Disc Areas) as delineated by ICGA.

Exclusion Criteria: - Participant

- Medical condition that, in the opinion of the investigator, would preclude participation in the study (e.g.unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

- Participation in an investigational trial within 30 days of enrollment which involves treatment with unapproved investigational drug.

- Known allergy to any component of the study drug.

- Blood pressure> 180/110 (systolic above 180 OR diastolic above 110 on repeated measurements). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.

- Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

- Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.

- Amblyopia or blind in one eye Study Eye

- Eye with intra retinal or sub-retinal fluid due to other causes than PCV

- An ocular condition is present (other than PCV) that, in the opinion of the investigator, might affect intra or sub retinal fluid or alter visual acuity during the course of the study (e.g., Diabetic Macular Edema (DME), vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)

- Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by more than three lines (i.e., cataract would be reducing acuity to worse than 20/40 if eye was otherwise normal).

- Any intraocular surgery within 3 months of enrollment

- Treatment with intra vitreal corticosteroids

- History of retinal detachment or surgery for retinal detachment

- History of vitrectomy

- History of macular hole

- Evidence of vitreomacular traction that may preclude resolution of macular edema > 4 disc areas of intra/sub retinal hemorrhage

- Aphakia

- Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis

Other Eye

- Active intraocular inflammation

- History of uveitis

Geschlecht: All

Mindestalter: 50 Years

Maximales Alter: N/A

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Gemmy Cheung Chui Ming Principal Investigator Singapore National Eye Centre
Gesamtkontakt

Nachname: Gemmy Cheung Chui Ming

Telefon: 63227460

Email: gemmy.ch[email protected]

Ort
Einrichtung:
Singapore National Eye Centre | Singapore, 168751, Singapore
National University Hospital | Singapore, Singapore
Tan Tock Seng Hospital | Singapore, Singapore
Standort Länder

Singapore

Überprüfungsdatum

July 2020

Verantwortliche Partei

Art: Principal Investigator

Ermittlerzugehörigkeit: Singapore National Eye Centre

Vollständiger Name des Ermittlers: Gemmy Cheung Chui Ming

Ermittlertitel: Professor

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 2
Armgruppe

Etikette: Brolucizumab Monotherapy

Art: Active Comparator

Beschreibung: Patients with symptomatic macular PCV (n=80) as confirmed by Indocyanine green Angiography(ICGA) will be treated with a dose of 6mg/ 0.05ml of Brolucizumab through an intravitreal injection, at baseline. A minimum of 1 injection(baseline) followed by PRN with minimum retreatment interval of 4 weeks ( from Baseline to week 8) and then minimum of 8 weeks retreatment thereafter ( week 12-52). Primary endpoint at week 52. At each visit, subjects will be assessed based on BCVA, opthalmic examination, Optical Coherence Tomography (OCT) and Optical Coherence Tomography-Angiography (OCT-A).

Etikette: Aflibercept Monotherapy

Art: Active Comparator

Beschreibung: Patients with symptomatic macular PCV (n=80) as confirmed by Indocyanine green Angiography(ICGA) will be treated with a dose of Aflibercept 2mg/0.05ml through an intravitreal injection,at baseline. A minimum of 1 injection(baseline) followed by Pro re nata (PRN) with minimum retreatment interval of 4 weeks ( from baseline to week 8) and then a minimum of 8 weeks retreatment thereafter ( week 12-52). Primary endpoint at week 52. At each visit, subjects will be assessed based on Best Corrected Visual Acuity (BCVA), opthalmic examination, Optical Coherence Tomography (OCT) and Optical Coherence Tomography-Angiography (OCT-A).

Patientendaten No
Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Beschreibung des Interventionsmodells: Multi-center randomized, double-masked clinical trial.

Hauptzweck: Treatment

Maskierung: Triple (Care Provider, Investigator, Outcomes Assessor)

Quelle: ClinicalTrials.gov