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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04423718




Registration number
NCT04423718
Ethics application status
Date submitted
8/06/2020
Date registered
9/06/2020

Titles & IDs
Public title
Study of the Effects of High Dose Aflibercept Injected Into the Eye of Patients With an Age-related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye
Scientific title
Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of High Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration
Secondary ID [1] 0 0
2019-003851-12
Secondary ID [2] 0 0
20968
Universal Trial Number (UTN)
Trial acronym
PULSAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neovascular Age-Related Macular Degeneration 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
Treatment: Drugs - Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)

Active comparator: Aflibercept 2q8 - In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental)

Experimental: Aflibercept HDq12 - Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.

Experimental: Aflibercept HDq16 - Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.


Treatment: Drugs: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
Solution in Vial, intravitreal (IVT) injection

Treatment: Drugs: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)
Solution in Vial, 2 mg, intravitreal (IVT) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48
Timepoint [1] 0 0
At baseline and Week 48
Secondary outcome [1] 0 0
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60
Timepoint [1] 0 0
At baseline and Week 60
Secondary outcome [2] 0 0
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16
Timepoint [2] 0 0
At Week 16
Secondary outcome [3] 0 0
Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48
Timepoint [3] 0 0
At baseline and Week 48
Secondary outcome [4] 0 0
Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48
Timepoint [4] 0 0
At Week 48
Secondary outcome [5] 0 0
Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48
Timepoint [5] 0 0
At baseline and Week 48
Secondary outcome [6] 0 0
Change in Total Lesion Area From Baseline to Week 48
Timepoint [6] 0 0
At baseline and Week 48
Secondary outcome [7] 0 0
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48
Timepoint [7] 0 0
At Week 48
Secondary outcome [8] 0 0
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48
Timepoint [8] 0 0
At baseline and Week 48
Secondary outcome [9] 0 0
Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48
Timepoint [9] 0 0
At baseline and Week 48
Secondary outcome [10] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
Timepoint [10] 0 0
Up to 156 weeks
Secondary outcome [11] 0 0
Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48
Timepoint [11] 0 0
Up to Week 48
Secondary outcome [12] 0 0
Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study
Timepoint [12] 0 0
Up to week 96

Eligibility
Key inclusion criteria
* Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye.
* Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye.
* BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye.
* Decrease in BCVA determined to be primarily the result of nAMD in the study eye.
* Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies.
* Other protocol-specified inclusion criteria.

Additional inclusion criteria for Year 3:

* At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92).
* Participant is enrolled at a site that participates in the extension period.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Causes of CNV other than nAMD in the study eye.
* Scar, fibrosis, or atrophy involving the central subfield in the study eye.
* Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye.
* Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye.
* History of idiopathic or autoimmune uveitis in the study eye.
* Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery.
* History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye.
* Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization.
* Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg).
* Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins.
* Other protocol-specified exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/08/2024
Sample size
Target
Accrual to date
Final
1011
Recruitment in Australia
Recruitment state(s)
NSW,TAS
Recruitment hospital [1] 0 0
Eyeclinic Albury Wodonga - Albury
Recruitment hospital [2] 0 0
Sydney Retina Clinic - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Hobart Eye Surgeons - Hobart
Recruitment hospital [5] 0 0
Marsden Eye Surgery Center - Parramatta
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2000 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
2150 - Parramatta
Recruitment outside Australia
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United States of America
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Arizona
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California
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Iowa
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Maryland
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Minnesota
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Kärnten
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Wien
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Sofia
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China
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China
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China
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Mie
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Tokushima
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Wakayama
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Yamagata
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Vilnius
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Coimbra
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Porto
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Moscow
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Serbia
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Belgrade
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Serbia
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Novi Sad
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Singapore
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Singapore
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Slovakia
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Nitra
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Slovakia
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Trebisov
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Trencin
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Slovakia
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Zilina
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Spain
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A Coruña
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Spain
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Barcelona
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Spain
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Córdoba
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Spain
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Valencia
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Spain
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Zaragoza
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Switzerland
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Vaud
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Switzerland
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Bern
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Switzerland
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Zürich
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Ukraine
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Kropyvnytskyi
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Ukraine
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Kyiv
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Ukraine
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Poltava

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04423718