Intravitreal Brolucizumab in Neovascular Age-related Macular Degeneration With Limited Response to Aflibercept

NCT04287348 | Terminated Phase 4

• 1 other identifier: ROBIN / CRTH258ACH01T
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this investigator initiated study is to identify the effects of intravitreal brolucizumab on recurrence-free treatment intervals and morphological features in choroidal neovascularizations (CNV) due to age-related macular degeneration (AMD) in which the Optical coherence tomography (OCT) guided treatment interval failed to be extended to 6, 8 or 10 weeks intervals in a treat and extend regimen using aflibercept.

Conditions

Neovascular Age-related Macular Degeneration

Keywords

AMD, poor responders, aflibercept, brolucizumab

Outcome Measures

Primary Outcomes (1)

• The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12.

  mean maximum treatment interval with intravitreal brolucizumab

  up to month 12

Secondary Outcomes (11)

• Best corrected visual acuity (BCVA) in letters

  month 6 and 12

• Number of brolucizumab intravitreal treatments applied during the 12 months study period.

  12 months

• Central retinal thickness (CRT, in µm) as measured in the central ETDRS subfield Spectral-Domain Optical coherence tomography (SD-OCT) at baseline, month 6 and 12.

  month 6 and 12

• Presence of qualitative SD-OCT features like intraretinal fluid, subretinal fluid, pigment epithelial detachment and hyperreflective foci at baseline, month 6 and 12

  month 6 and 12

• Total CNV area and vessel density as measured by OCTangiography (OCTA) at baseline, month 6 and 12.

  month 6 and 12

Study Arms (1)

Beovu (Brolucizumab)

OTHER

Prospective, one-treatment-arm, monocentre study

Drug: Brolucizumab 6 mg solution for intravitreal injection

Interventions

Brolucizumab 6 mg solution for intravitreal injection DRUG

All consenting, enrolled patients (irrespectively of maximum recurrence-free interval under aflibercept pretreatment) will receive an intravitreal injection of brolucizumab 6 mg at baseline (week 0), at week 4 and each of the following treat and extend visits. At each visit all patients will undergo an OCT assessment. For all patients extension of treatment intervals is only possible 2-week-stepwise, e.g. 4, 6, 8 weeks etc.

Also known as: Beovu

Beovu (Brolucizumab)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 50 years of age.
• Patients with active subfoveal or juxtafoveal Type 1, 2 or 3 CNV secondary to AMD.
• Pre-treatment with intravitreal aflibercept in a treat and extend regimen with 2-weeks steps and failing to be extended by two weeks to either 6-weeks intervals, 8 week intervals or 10 week intervals without showing CNV activity (at least 2 attempts to extend).
• The total area of CNV (including both classic and occult components) encompassed within the lesion must be ≥ 50% of the total lesion area.
• The total lesion area ≤ 12 disc areas for minimally classic or occult with no classic component and ≤ 9 disc areas (5400μm) in greatest linear dimension with predominantly classic lesions.
• Patients who have a BCVA of at least 20/160 (letter score 40 letters) in the study eye using ETDRS charts.
• Willing and able to comply with study procedures.

You may not qualify if:

• Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either ≥ 50% of the total lesion area or ≥ 1 disc area in size.
• Presence of a retinal pigment epithelial tear involving the fovea in the study eye.
• Patients with angioid streaks or precursors of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.
• Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the 12 months study period.
• Vitreous hemorrhage or history of retinal detachment or macular hole (Stage 3 or 4) in the study eye.
• Active intraocular inflammation (grade trace or above) in the study eye.
• Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye.
• History of uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication).
• Aphakia with absence of the posterior capsule in the study eye.
• Any prior treatment in the study eye with radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, transpupillary thermotherapy.
• History of submacular surgery or other surgical intervention for AMD in the study eye, glaucoma filtration surgery, corneal transplant surgery.
• Extracapsular extraction of cataract with phacoemulsification within three months preceding Baseline, or a history of post-operative complications within the last 12 months preceding Baseline in the study eye (uveitis, cyclitis, etc.).
• Use of other investigational drugs at the time of baseline, or within 30 days or 5 half- lives of baseline, whichever is longer (excluding vitamins and minerals).
• Previous violation of the posterior capsule in the study eye unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.

Sponsors & Collaborators

• Vista Klinik: lead
• Novartis: collaborator

Study Sites (1)

Vista Klinik

Binningen, Basel-Landschaft, 4102, Switzerland

Location

MeSH Terms

Interventions

brolucizumab; Solutions; Intravitreal Injections

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Injections, Intraocular; Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Katja Hatz, PD Dr. med

  Vista Klinik Binningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Medical Retina and clinical Research department

Model Details: Prospective, one-treatment-arm, monocentre study

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 27, 2020
• Study Start: July 20, 2020
• Primary Completion: November 22, 2021
• Study Completion: November 22, 2021
• Last Updated: December 29, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)