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Age-related Macular Degeneration (AMD)Phase 3PEREGRINENCT04697953

Efficacy and Safety of Brolucizumab 6mg in a Treat and Extend Regimen in Patients With Neovascular Age-Related Macular Degeneration (nAMD) With Prior Anti-VEGF Exposure (PEREGRINE)

A Phase 3 study testing brolucizumab in people with Age-related Macular Degeneration (AMD), run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to assess whether switching nAMD patients from aflibercept to brolucizumab would permit extension of treatment intervals while maintaining treatment efficacy, thereby alleviating the treatment burden on patients, caregivers, healthcare professionals (HCPs), and medical institutions. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Age-related Macular Degeneration (AMD)
What is being tested?
brolucizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
31 May 2021to 31 May 2025
Phase
Phase 3
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

  • Written informed consent must be obtained personally or by a legal proxy before any assessment is performed.
  • Patients who are ≥ 50 years of age
  • Confirmed diagnosis of nAMD in the judgement of the investigator
  • Patients currently being treated with intravitreal injections of aflibercept 2 mg on 6-12 week dosing intervals for nAMD for a period no longer than 24 months from date of diagnosis.
  • Documentation of at least one attempt to extend past the current dosing interval of aflibercept 2mg and return to stable condition at the current predefined interval
  • BCVA score must be ≤ 78 (20/32) and ≥24 (20/320) letters using Early Treatment Diabetic Retinopathy Study (EDTRS)-like visual acuity charts at baseline

Who cannot join

  • nAMD patients with disease activity at baseline
  • Concomitant conditions or ocular disorders in the study eye at 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 planned medical or surgical intervention during the first 12-month study period.
  • Simultaneous participation in a study that includes administration of any investigational drug or procedure, other than brolucizumab.
  • Any active intraocular or periocular infection or active intraocular inflammation, at baseline (study eye) or in the preceding 6 months
  • Uncontrolled glaucoma defined as intraocular pressure > 25 mmHg on medication, or according to investigator's judgment, at baseline (study eye)
  • Patient having a fellow eye with BCVA < 20/200 at baseline due to any causes (except when due to conditions that can lead to improved VA after surgery, e.g. cataract)
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  • Patients who have been previously treated with brolucizumab in either eye, or who are currently receiving brolucizumab treatment in the fellow eye
  • Patients who have been treated with aflibercept longer than 24 months.
  • Previous use of intraocular or periocular steroids within the 6-months prior to baseline (study eye)
  • Macular laser photocoagulation (focal/grid) or photodynamic therapy (PDT) at any time prior to baseline and peripheral laser photocoagulation within 3 months prior to baseline (study eye)
  • Intraocular surgery within 3 months prior to baseline (except cataract; study eye) Vitreoretinal surgery at any time prior to baseline (study eye)

About this study

Official title: Brolucizumab Switch and Extend Ph IIIb Study: A Canadian, Multi-center, Single-arm, Open Label Study Assessing the Efficacy and Safety of Brolucizumab 6mg in a Treat and Extend Regimen in Patients With Neovascular Age-Related Macular Degeneration (nAMD) With Prior Anti-VEGF Exposure (PEREGRINE)

The purpose of this study is to assess whether switching nAMD patients from aflibercept to brolucizumab would permit extension of treatment intervals while maintaining treatment efficacy, thereby alleviating the treatment burden on patients, caregivers, healthcare professionals (HCPs), and medical institutions.

Read the detailed description

This study is a 104 week, single-arm, open label, Ph IIIb multicenter study in Canadian nAMD patients who will be switched from aflibercept 2mg to brolucizumab 6mg and extended using a Treat \& Extend regimen by up to 2 week intervals assessing the durability, effectiveness, and safety of brolucizumab 6mg.

During the baseline visit, patients who consent will undergo an assessment to evaluate their eligibility based on the inclusion and exclusion criteria. Patients that meet all of the inclusion criteria and none of the exclusion criteria will be eligible to participate. The study is expected to recruit 423 patients.

If both eyes are eligible as per the inclusion and exclusion criteria, the eye with worse visual acuity should be selected for the study eye, unless the investigator deems it more appropriate to select the eye with better visual acuity.

nAMD patients stable on aflibercept q6w, q8w, q10w or q12w, will be switched to brolucizumab 6mg intravitreal injections. Disease stability is characterized by no disease activity based on the disease activity assessment (DAA) criteria (defined below) and on the investigator's judgment of visual function and/or anatomic outcomes (e.g. no change in visual acuity) or any other signs of the disease (e.g. SRF, hemorrhage, leakage, etc.).

At baseline patients will be treated with brolucizumab 6mg in the study eye only and will be scheduled for the next treatment at the pre-baseline dosing interval.

At subsequent visits, the treating physician will perform a disease activity assessment (DAA) to establish treatment extension based on the following criteria:

  • Decrease in BCVA of ≥ 5 letters compared to previous visit or,
  • Decrease in BCVA of ≥ 3 letters and CSFT increase ≥ 75μm compared to previous visit or,
  • Any intraretinal cysts (IRC) / intraretinal fluid (IRF) compared to previous visit If the treating physician determines that there is no nAMD disease activity based on visual and anatomical assessments, i.e. no change in visual acuity and other signs of disease (e.g. IRF, SRF, hemorrhage or leakage), the following treatment can be extended by up to 2 weeks. Treatment extensions can occur at each subsequent visit to a maximum of 20 weeks between treatments.

If disease activity is identified at any study visit the interval should be shortened. If the patient is on a dosing regimen of q12w or less, the dosing interval will be shortened by two (2) weeks. For patients on a regimen of greater than q12w, the dosing interval will be shortened by four (4) weeks. If the treatment interval is currently q6w and patient fails DAA, they are not forced to discontinue, and they can be reduced to a treatment interval below q6w.

If a patient fails the first attempt to extend, the patient will have two more attempts for extension during the study.

If the patient shows significant disease activity after the second attempt for extension, injection intervals will be fixed to the previous stable, disease free interval until the end of the study.

At any point during the study, the treatment interval can also be maintained, if the investigator deems that the patient will not benefit from treatment interval adjustment (e.g., DAA due to reasons other than nAMD disease activity [e.g. fibrosis, geographic atrophy, etc.]).

Being tested
brolucizumab
Keywords
neovascular age-related macular degeneration
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • brolucizumabDrug

    Pre-filled Syringes for intravitreal injection

Study groups in NCT04697953
Study groupRoleWhat they receive
brolucizumab 6mgExperimentalOpen label, brolucizumab 6mg, daily dosing, Treat \& Extend regimen by up to 2 week intervals. Dosing intervals as per previous therapy and treatment extension intervals
Receives: Drug: brolucizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion (%) of patients switched from aflibercept 2 mg to brolucizumab 6mg that were able to successfully extend their dosing interval at week 52 without incurring disease activity after switching

    To evaluate if Neovascular Age-related Macular Degeneration (nAMD) patients can extend treatment intervals after switching from 2mg aflibercept to 6mg brolucizumab, while maintaining treatment effectiveness

    Measured: 104 weeks

Secondary outcomes (10)
  1. Mean maximum interval (number of weeks) of patients at week 104

    To evaluate dosing intervals and durability of brolucizumab 6mg used in a Treat and Extend regimen after switching from aflibercept 2mg

    Measured: Up to 104 weeks

  2. The % of patients switched from aflibercept 2 mg to brolucizumab 6mg that were able to extend their dosing interval at week 104

    To evaluate dosing intervals and durability of brolucizumab 6mg used in a Treat and Extend regimen after switching from aflibercept 2mg

    Measured: up to 104 weeks

  3. The % of patients switched from aflibercept 2 mg to brolucizumab 6mg that were able to maintain or extend their dosing interval at week 52 and 104

    To evaluate dosing intervals and durability of brolucizumab 6mg used in a Treat and Extend regimen after switching from aflibercept 2mg

    Measured: up to 104 weeks

  4. Mean interval (number of weeks) of patients after switch reached at any given time point at week 52 and 104

    To evaluate dosing intervals and durability of brolucizumab 6mg used in a Treat and Extend regimen after switching from aflibercept 2mg

    Measured: up to 104 weeks

  5. Mean change in Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (EDTRS letters) from baseline to week 52, and 104

    To evaluate changes in visual outcomes with brolucizumab after switching from aflibercept throughout the study in comparison to baseline assessments.

    Measured: up to 104 weeks

  6. The % of patients with a change in BCVA (EDTRS letters) of 5, 10, 15 letters or more from baseline to week 52, and 104

    To evaluate changes in visual outcomes with brolucizumab after switching from aflibercept throughout the study in comparison to baseline assessments

    Measured: up to 104 weeks

  7. The % of patients with any intraretinal fluid (IRF) and/or subretinal fluid (SRF) at baseline, weeks 52, and 104

    To evaluate changes of anatomical outcomes with brolucizumab after switching from aflibercept throughout the study in comparison to baseline assessments.

    Measured: up to 104 weeks

  8. Incidence of ocular (e.g., intraocular infection) and non-ocular adverse events, vital signs up to week 52, and 104

    To evaluate safety and tolerability of treat and extend brolucizumab 6mg dosing

    Measured: up to 104 weeks

  9. Mean change from baseline in central subfield foveal thickness (CSFT)

    To evaluate changes of anatomical outcomes with brolucizumab after switching from aflibercept throughout the study in comparison to baseline assessments.

    Measured: at weeks 52, 104

  10. The % of patients with pigment epithelial detachment (PED)

    To evaluate changes of anatomical outcomes with brolucizumab after switching from aflibercept throughout the study in comparison to baseline assessments.

    Measured: at baseline, weeks 52, 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2021
  2. Study start31 May 2021 (estimated)
  3. Primary completion21 Jun 2021 (estimated)
  4. Study completion31 May 2025 (estimated)

Why it stopped: Study terminated - no participants were enrolled.

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Study design This study is a 104-week, single arm, open label, Ph IIIb multicenter study in Canadian nAMD patients. Neovascular AMD patients will be switched from aflibercept Q6-12W to brolucizumab at the same dosing interval at baseline. At the second visit the treating physician will conduct a disease activity assessment. If patient is stable, treatment will be extended by up to two (2) weeks using a Treat and Extend regimen interval. If the patient remains stable, the extension will also occur at next visits until maximum of Q20 Weeks.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04697953
Sponsor's protocol ID
CRTH258ACA03
Acronym
PEREGRINE
Status last verified
Sep 2021
First submitted
30 Nov 2020
Last updated
23 Sep 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing brolucizumab in people with Age-related Macular Degeneration (AMD), run by Novartis Pharmaceuticals.

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 6 inclusion and 11 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: withdrawn, as of the sponsor's last update on 23 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 withdrawn before enrolling participants, so there are no results.

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 proportion (%) of patients switched from aflibercept 2 mg to brolucizumab 6mg that were able to successfully extend their dosing interval at week 52 without incurring disease activity after switching (time frame: 104 weeks). 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 23 Sep 2021.

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