Neovascular Age-related Macular DegenerationPhase 4ROBINNCT04287348
Intravitreal Brolucizumab in Neovascular Age-related Macular Degeneration With Limited Response to Aflibercept
A Phase 4 study testing Brolucizumab 6 mg solution for intravitreal injection in people with Neovascular Age-related Macular Degeneration, run by Vista Klinik at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascular Age-related Macular Degeneration
- What is being tested?
- Brolucizumab 6 mg solution for intravitreal injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Jul 2020to 22 Nov 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 give written informed consent according to legal requirements, and who have signed the consent form prior to initiation of any study procedure including withdrawal from exclusionary medications for the purpose of this study.
- Willing and able to comply with study procedures.
Who cannot join
- 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.
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- 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.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/ml).
- History of hypersensitivity or allergy to fluorescein.
- Inability to obtain OCTs, OCTAs, fundus photographs or fluorescein angiograms of sufficient quality.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Outcome Measures:
The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12.
The secondary outcomes are:
- Best corrected visual acuity (BCVA) in letters and BCVA change (letters) from baseline (=switch to brolucizumab) to month 6 and 12.
- Number of brolucizumab intravitreal treatments applied during the 12 months study period.
- 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.
- Presence of qualitative SD-OCT features like intraretinal fluid, subretinal fluid, pigment epithelial detachment and hyperreflective foci at baseline, month 6 and 12.
- Total CNV area and vessel density as measured by OCTangiography (OCTA) at baseline, month 6 and 12.
- Total area of leakage from CNV and the total lesion area as evaluated by Fluorescein angiography (FA) at baseline and month 12.
- VFQ-25 total and subscores as evaluated by quality of life questionnaire VFQ-25 at baseline and month 6 and 12.
- Rates of adverse events and serious adverse events at 6 and 12 months.
- Being tested
- Brolucizumab 6 mg solution for intravitreal injection
- Keywords
- AMD, poor responders, aflibercept, brolucizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brolucizumab 6 mg solution for intravitreal injectionDrug
Also called Beovu
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.
| Study group | Role | What they receive |
|---|---|---|
| Beovu (Brolucizumab) | Other | Prospective, one-treatment-arm, monocentre study Receives: Drug: Brolucizumab 6 mg solution for intravitreal injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12.
mean maximum treatment interval with intravitreal brolucizumab
Measured: up to month 12
Secondary outcomes (11)
Best corrected visual acuity (BCVA) in letters
BCVA
Measured: month 6 and 12
Number of brolucizumab intravitreal treatments applied during the 12 months study period.
Number of brolucizumab
Measured: 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.
CRT
Measured: 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
SD-OCT
Measured: month 6 and 12
Total CNV area and vessel density as measured by OCTangiography (OCTA) at baseline, month 6 and 12.
Total CNV area and vessel density
Measured: month 6 and 12
Total area of leakage from CNV
Total area of leakage from CNV
Measured: baseline and month 12
VFQ-25 total evaluated by quality of life questionnaire VFQ-25 at baseline and month 6 and 12.
VFQ-25
Measured: month 6 and 12
Rates of adverse events and serious adverse events at 6 and 12 months.
AE and SAE
Measured: 6 and 12 months.
BCVA change (letters) from baseline (=switch to brolucizumab)
BCVA
Measured: month 6 and 12
the total lesion area as evaluated by Fluorescein angiography (FA) at baseline and month 12
Total area of leakage from CNV
Measured: baseline and month 12
VFQ-25 subscores
VFQ-25 subscores
Measured: month 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start20 Jul 2020
- Primary completion22 Nov 2021
- Study completion22 Nov 2021
Why it stopped: due to safety letter beovu from Novartis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neovascular Age-related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, one-treatment-arm, monocentre study
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vista Klinik
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, PD Dr. med. Katja Hatz, Vista Klinik
- Investigators
- Katja Hatz, PD Dr. med, Principal investigator, Vista Klinik Binningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04287348
- Sponsor's protocol ID
- ROBIN / CRTH258ACH01T
- Acronym
- ROBIN
- Status last verified
- Dec 2021
- First submitted
- 21 Feb 2020
- Last updated
- 29 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravitreal Brolucizumab in Neovascular Age-related Macular Degeneration With Limited Response to Aflibercept
- ClinicalTrials.gov ID
- NCT04287348
- Acronym / sponsor ID
- ROBIN / ROBIN / CRTH258ACH01T
- Keywords
- AMD, poor responders, aflibercept, brolucizumab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to safety letter beovu from Novartis
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Vista KlinikUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 20 Jul 2020 (actual)
- Primary completion
- 22 Nov 2021 (actual)
- Study completion
- 22 Nov 2021 (actual)
- First posted
- 27 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Outcome Measures:
The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12.
The secondary outcomes are:
- Best corrected visual acuity (BCVA) in letters and BCVA change (letters) from baseline (=switch to brolucizumab) to month 6 and 12.
- Number of brolucizumab intravitreal treatments applied during the 12 months study period.
- 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.
- Presence of qualitative SD-OCT features like intraretinal fluid, subretinal fluid, pigment epithelial detachment and hyperreflective foci at baseline, month 6 and 12.
- Total CNV area and vessel density as measured by OCTangiography (OCTA) at baseline, month 6 and 12.
- Total area of leakage from CNV and the total lesion area as evaluated by Fluorescein angiography (FA) at baseline and month 12.
- VFQ-25 total and subscores as evaluated by quality of life questionnaire VFQ-25 at baseline and month 6 and 12.
- Rates of adverse events and serious adverse events at 6 and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, one-treatment-arm, monocentre study
| Arm | Type | Receives |
|---|---|---|
| Beovu (Brolucizumab) | Other | Drug: Brolucizumab 6 mg solution for intravitreal injectionProspective, one-treatment-arm, monocentre study |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brolucizumab 6 mg solution for intravitreal injectionAlso: BeovuAll 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. | Drug | Beovu (Brolucizumab) |
Primary outcome
The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12.
Time frame: up to month 12
mean maximum treatment interval with intravitreal brolucizumab
11 secondary outcomes
Best corrected visual acuity (BCVA) in letters
Time frame: month 6 and 12
Number of brolucizumab intravitreal treatments applied during the 12 months study period.
Time frame: 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.
Time frame: 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
Time frame: month 6 and 12
Total CNV area and vessel density as measured by OCTangiography (OCTA) at baseline, month 6 and 12.
Time frame: month 6 and 12
Total area of leakage from CNV
Time frame: baseline and month 12
VFQ-25 total evaluated by quality of life questionnaire VFQ-25 at baseline and month 6 and 12.
Time frame: month 6 and 12
Rates of adverse events and serious adverse events at 6 and 12 months.
Time frame: 6 and 12 months.
BCVA change (letters) from baseline (=switch to brolucizumab)
Time frame: month 6 and 12
the total lesion area as evaluated by Fluorescein angiography (FA) at baseline and month 12
Time frame: baseline and month 12
VFQ-25 subscores
Time frame: month 6 and 12
Results and safety
The study was stopped early (reason given: due to safety letter beovu from Novartis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katja Hatz, PD Dr. med principal investigator
Vista Klinik Binningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Brolucizumab 6 mg solution for intravitreal injection in people with Neovascular Age-related Macular Degeneration, run by Vista Klinik at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: due to safety letter beovu from Novartis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome is the mean maximum treatment interval with intravitreal brolucizumab at month 6 and 12. (time frame: up to month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2021.