Ignite Creation Date:
2025-12-24 @ 4:45 PM
Ignite Modification Date:
2025-12-28 @ 6:25 PM
Study NCT ID:
NCT04698850
Status:
WITHDRAWN
Last Update Posted:
2022-08-10
First Post:
2021-01-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Brolucizumab vs. Aflibercept for Retinal Angiomatous Proliferation
Sponsor:
Faculty Hospital Kralovske Vinohrady
Organization:
Study Overview
Official Title:
Brolucizumab vs. Aflibercept for Retinal Angiomatous Proliferation - Prospective Randomised Study
Status:
WITHDRAWN
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
funding issues
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BEY-RAP
Brief Summary:
This is a prospective randomised study comparing two intravitreal antiVEGF drugs - brolucizumab and aflibercept - in the treatment of retinal angiomatous proliferation (RAP). Patients with RAP confirmed on optical coherence tomography (OCT) and on OCT angiography (OCTA) will be randomised in two groups and followed for 52 weeks.
Patients in the first group will receive aflibercept - 3 injections monthly for the first 3 months and then in treat-and-extend regimen with minimal interval of 8 weeks and maximal interval of 16 weeks. Extension or shortening of the therapeutic interval will be possible in 2 or 4 week increments based on the visual acuity and disease activity assessed on OCT.
Patients in the second group will receive brolucizumab - 3 injections monthly in the first 3 months and then every 2 or 3 months based on the visual acuity and disease activity assessed on OCT.
Best corrected visual acuity (BCVA), central retinal thickness (CRT) on OCT and number of injections will be compared between both groups.
Patients in the first group will receive aflibercept - 3 injections monthly for the first 3 months and then in treat-and-extend regimen with minimal interval of 8 weeks and maximal interval of 16 weeks. Extension or shortening of the therapeutic interval will be possible in 2 or 4 week increments based on the visual acuity and disease activity assessed on OCT.
Patients in the second group will receive brolucizumab - 3 injections monthly in the first 3 months and then every 2 or 3 months based on the visual acuity and disease activity assessed on OCT.
Best corrected visual acuity (BCVA), central retinal thickness (CRT) on OCT and number of injections will be compared between both groups.
Detailed Description:
Retinal angiomatous proliferation (RAP) is one of the variants of wet form of age-related macular degeneration (wAMD). Neovascularization in RAP grows from the retinal deep capillary plexus into the subretinal space where it forms subretinal and later choroidal neovascularization. It is often accompanied with high macular edema and pigment epithelium detachment (PED). As with other forms of wAMD, treatment with intravitreal antiVEGF drugs is highly effective. In our study, we would like to compare the efficacy of 2 antiVEGF drugs - aflibercept and brolucizumab - in the treatment of RAP.
This is a prospective, randomised, comparative study comparing the best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) in the 16th, 26th and 52nd week of the study between patients with RAP treated with aflibercept and brolucizumab. In the 52nd week, the total number of injections between both groups will be also compared.
Visit plan:
Screening visit - 14 to 1 day prior to baseline. Informed consent will be signed prior to any other study procedures. Ocular and medical history will be written down. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT and OCTA of both eyes will be performed. Colour fundus photograph (FP) and red-free (RF) FP of the macula of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed.
Baseline - day 1 - VFQ-25 questionnaire will be done with the patient. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed. Eligible patients will be randomised and study medication will be given.
Week 4, Week 8 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given.
Week 16 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Study medication will be given. Next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA:
1. group - aflibercept - treatment interval can be left on 8 weeks or extended by 2 or 4 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
2. group - brolucizumab - aflibercept - treatment interval can be left on 8 weeks or prolonged to 12 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
Week 24 to week 48 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given. Next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA:
1. group - aflibercept - treatment interval can be extended or shortened by 2 or 4 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Maximal treatment interval can be 16 weeks, minimal 8 weeks. Final decision is on the investigator.
2. group - brolucizumab - aflibercept - treatment interval can be set to 8 or 12 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
W26 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Study medication will be given and next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA if planned based on patients treatment schedule.
W52 - VFQ-25 questionnaire will be done with the patient. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Colour fundus photograph (FP) and red-free (RF) FP of the macula of both eyes will be performed.
Study procedures:
OCT - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). CRT will be assessed from automatic retinal thickness analysis in 9 ETDRS subfields including the central subfield. 49 horizontal scans in the angle of 20x20° 123 um apart in High resolution mode with noise reduction set to ART=4 will be performed.
OCTA - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). 512 horizontal scans in the angle of 20x20° 11 um apart in High speed mode with noise reduction set to ART=5 will be performed.
Disease activity assessment:
Based on the decision of the investigator. Shortening of the treatment interval is recommended when the BCVA decrease of more than 5 ETDRS letters is observed, in case of intra- or subretinal fluid or PED reappearance or increase on the OCT or when new haemorrhage or hard exudates are observed in the macula.
Extension of the treatment interval is recommended in the absence of intra- and subretinal fluid and PED on the OCT with better or stable BCVA, or in case the BCVA and OCT findings are stable after 3 injections in the shortest possible interval.
Rescue therapy:
Ranibizumab may be given as a rescue therapy in case of patients with study drug related sight threatening adverse events or with worsening of BCVA and OCT findings even on the shortest treatment interval when resistance to study drug is suspected. Switch to rescue therapy must be consulted with and approved by principal investigator.
This is a prospective, randomised, comparative study comparing the best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) in the 16th, 26th and 52nd week of the study between patients with RAP treated with aflibercept and brolucizumab. In the 52nd week, the total number of injections between both groups will be also compared.
Visit plan:
Screening visit - 14 to 1 day prior to baseline. Informed consent will be signed prior to any other study procedures. Ocular and medical history will be written down. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT and OCTA of both eyes will be performed. Colour fundus photograph (FP) and red-free (RF) FP of the macula of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed.
Baseline - day 1 - VFQ-25 questionnaire will be done with the patient. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Based on the examination results, patients eligibility for the study will be assessed. Eligible patients will be randomised and study medication will be given.
Week 4, Week 8 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given.
Week 16 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Study medication will be given. Next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA:
1. group - aflibercept - treatment interval can be left on 8 weeks or extended by 2 or 4 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
2. group - brolucizumab - aflibercept - treatment interval can be left on 8 weeks or prolonged to 12 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
Week 24 to week 48 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given. Next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA:
1. group - aflibercept - treatment interval can be extended or shortened by 2 or 4 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Maximal treatment interval can be 16 weeks, minimal 8 weeks. Final decision is on the investigator.
2. group - brolucizumab - aflibercept - treatment interval can be set to 8 or 12 weeks based on the presence or absence of subretinal or intraretinal fluid or PED on the OCT, on the BCVA and on the presence of other signs of disease activity on the fundus examination (e.g. haemorrhage, hard exudates). Final decision is on the investigator.
W26 - adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Study medication will be given and next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA if planned based on patients treatment schedule.
W52 - VFQ-25 questionnaire will be done with the patient. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed. Colour fundus photograph (FP) and red-free (RF) FP of the macula of both eyes will be performed.
Study procedures:
OCT - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). CRT will be assessed from automatic retinal thickness analysis in 9 ETDRS subfields including the central subfield. 49 horizontal scans in the angle of 20x20° 123 um apart in High resolution mode with noise reduction set to ART=4 will be performed.
OCTA - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). 512 horizontal scans in the angle of 20x20° 11 um apart in High speed mode with noise reduction set to ART=5 will be performed.
Disease activity assessment:
Based on the decision of the investigator. Shortening of the treatment interval is recommended when the BCVA decrease of more than 5 ETDRS letters is observed, in case of intra- or subretinal fluid or PED reappearance or increase on the OCT or when new haemorrhage or hard exudates are observed in the macula.
Extension of the treatment interval is recommended in the absence of intra- and subretinal fluid and PED on the OCT with better or stable BCVA, or in case the BCVA and OCT findings are stable after 3 injections in the shortest possible interval.
Rescue therapy:
Ranibizumab may be given as a rescue therapy in case of patients with study drug related sight threatening adverse events or with worsening of BCVA and OCT findings even on the shortest treatment interval when resistance to study drug is suspected. Switch to rescue therapy must be consulted with and approved by principal investigator.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: