Neovascular Age-Related Macular Degeneration (nAMD)Phase 34FRONT-2NCT07064759
Single Intravitreal (IVT) Injection of 4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration
A Phase 3 study testing 4D-150 IVT (3E10 vg/eye) and EYLEA® (aflibercept) Injection 2 mg (0.05mL) in people with Neovascular Age-Related Macular Degeneration (nAMD), run by 4D Molecular Therapeutics at 126 sites in 17 countries.
Trial summary
This Phase 3 study is evaluating the safety and efficacy of 4D-150 versus aflibercept in participants with neovascular age-related macular degeneration (nAMD). Enrollment in the primary global cohort has been completed; Study centers in Japan remain open for enrollment for the Japan cohort. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascular Age-Related Macular Degeneration (nAMD)
- What is being tested?
- 4D-150 IVT (3E10 vg/eye) and EYLEA® (aflibercept) Injection 2 mg (0.05mL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 480 participants
- Where
- 126 sitesin 17 countries
- Study dates
- 22 Jul 2025to Nov 2029
- Phase
- Phase 3
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
- ≥50 years of age at time of consent
- MNV secondary to nAMD with IVT anti-VEGF treatment history in the study eye, defined as EITHER:
- Treatment naïve, i.e. no prior IVT anti-VEGF therapy OR
- Previously treated with no more than 4 IVT anti-VEGF injections due to nAMD and received diagnosis of nAMD no more than 6 months prior to the Screening Visit AND documented evidence of anatomical improvement and visual stability/improvement in response to previous IVT anti-VEGF treatment, as determined by the Investigator
- Active subfoveal MNV or juxtafoveal/ extrafoveal MNV with a subfoveal component (where activity is defined as evidence of SRF, IRF, subretinal hyperreflective material, or leakage) identified by fluorescein angiography (FA) or spectral domain optical coherence tomography (SD-OCT) , in the study eye, at the Screening Visit confirmed by the Reading Center
- Demonstrated clinical response to aflibercept and functional stability in the study eye as confirmed by the Reading Center
- BCVA between 25 and 78 ETDRS letters, inclusive (20/320-20/32 Snellen equivalent) in the study eye at the Screening Visit
- CST less than or equal to 500 microns in the study eye at screening visit, confirmed by the central reading center
Who cannot join
- Ocular Conditions:
- MNV due to causes other than nAMD in either eye (Fibrosis, atrophy, or subretinal hemorrhage in the foveal central subfield (1 mm diameter)
- History of retinal detachment in the study eye
- History of or presence of active inflammation in either eye
- Glaucoma or intraocular hypertension requiring more than 2 topical medications for control
- Ocular Treatments/Interventions:
Show all 12Show fewer
- Any prior or concomitant treatment for MNV or vitreomacular-interface abnormalities, other than allowed prior IVT anti-VEGF in the study eye
- Systemic Conditions and Considerations:
- Major illness or major surgical procedure in the 28 days prior to the Screening Visit
- Uncontrolled blood pressure
- Acute coronary syndrome, myocardial infarction or coronary artery revascularization, cerebrovascular accident, transient ischemic attack within 6 months of the Screening Visit
- History of autoimmune condition that may predispose to the development of uveitis
Trial locations and contacts
126 sites in 17 countries. Contact the study team or a site near you to ask about taking part.
126 sites in 17 countries
United States60 sites
- Active, not recruiting
Southwest Retina Specialist - Panhandle Eye group, LLP
Amarillo, Texas, 79106
- Active, not recruiting
Austin Clinical Research
Austin, Texas, 78750
- Active, not recruiting
The Retina Care Center
Baltimore, Maryland, 21209
- Active, not recruiting
Envision Ocular, LLC
Bloomfield, New Jersey, 07003
- Active, not recruiting
Charleston Neuroscience Institute, LLC
Bluffton, South Carolina, 29910
- Active, not recruiting
Retinal Diagnostic Center
Campbell, California, 95008
- Active, not recruiting
Retina Partners Midwest, PC
Carmel, Indiana, 46032
- Active, not recruiting
North Carolina Retina Associates
Cary, North Carolina, 27511
- Active, not recruiting
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
- Active, not recruiting
Retina Consultants of Southern Colorado P.C.
Colorado Springs, Colorado, 80909
- Active, not recruiting
Texas Retina Associate
Dallas, Texas, 75231
- Active, not recruiting
Retina Specialists of Colorado
Denver, Colorado, 80222
- Active, not recruiting
Southwest Retina Consultants
Durango, Colorado, 81303
- Active, not recruiting
Retina Associates, Ltd.
Elmhurst, Illinois, 60126
- Active, not recruiting
Erie Retina Research
Erie, Pennsylvania, 16505
- Active, not recruiting
Verum Research, LLC
Eugene, Oregon, 947401
- Active, not recruiting
Retina Consultants of Orange County
Fullerton, California, 92835
- Active, not recruiting
Foundation for Vision Research
Grand Rapids, Michigan, 49546
- Active, not recruiting
Cumberland Valley Retina Consultants
Hagerstown, Maryland, 21740
- Active, not recruiting
Mid Atlantic Retina Specialists
Hagerstown, Maryland, 21740
- Active, not recruiting
ClearVista Clinical Research
Hudson, Florida, 34667
- Active, not recruiting
Southeastern Retina Associates
Johnson City, Tennessee, 37604
- Active, not recruiting
Florida Retina Consultants
Lakeland, Florida, 33805
- Active, not recruiting
Retina Vitreous Surgeons of CNY PC
Liverpool, New York, 13088
- Active, not recruiting
Piedmont Eye Center
Lynchburg, Virginia, 24502
- Active, not recruiting
Northern California Retina Vitreous Associates
Mountain View, California, 94040
- Active, not recruiting
Carolina Eyecare Physicians
Mt. Pleasant, South Carolina, 29464
- Active, not recruiting
Tennessee Retina, PC
Nashville, Tennessee, 37203
- Active, not recruiting
New York Presbyterian Hospital - Columbia University Medical Center
New York, New York, 10032
- Active, not recruiting
University Retina and Macula Associates, PC
Oak Forest, Illinois, 60452
- Active, not recruiting
Illinois Retina Associates
Oak Park, Illinois, 60304
- Active, not recruiting
Florida Retina Institute
Orlando, Florida, 32806
- Active, not recruiting
Retina Specialty Institute
Pensacola, Florida, 32503
- Active, not recruiting
EyeHealth Northwest
Portland, Oregon, 97233
- Active, not recruiting
Black Hills Regional Eye Institute
Rapid City, South Dakota, 57701
- Active, not recruiting
Sierra Eye Associates
Reno, Nevada, 89502
- Active, not recruiting
Retinal Consultants Medical Group Inc.
Sacramento, California, 95825
- Active, not recruiting
Retinal Consultants Medical Group
Sacramento, California, 95841
- Active, not recruiting
Rocky Mountain Retina Consultants
Salt Lake City, Utah, 84107
- Active, not recruiting
West Coast Retina Medical Group
San Francisco, California, 94109
- Active, not recruiting
Austin Retina Associates
San Marcos, Texas, 78666
- Active, not recruiting
Thomas Eye Group
Sandy Springs, Georgia, 30328
- Active, not recruiting
Research Network Arizona
Scottsdale, Arizona, 85255
- Active, not recruiting
Pacific Northwest Retina
Silverdale, Washington, 98383
- Active, not recruiting
Springfield Clinic
Springfield, Illinois, 62703
- Active, not recruiting
New England Retina Consultants
Springfield, Massachusetts, 01107
- Active, not recruiting
The Retina Institute
St Louis, Missouri, 63128
- Active, not recruiting
Retina Vitreous Associates of Florida
St. Petersburg, Florida, 33711
- Active, not recruiting
East Florida Eye Institute
Stuart, Florida, 34994
- Active, not recruiting
Barnet Dulaney Perkins Eye Center
Sun City, Arizona, 85351
- Active, not recruiting
Retina Vitreous Associates of Florida
Tampa, Florida, 33617
- Active, not recruiting
Retina Associates
Tucson, Arizona, 85704
- Active, not recruiting
Tyler Retina Consultants
Tyler, Texas, 75703
- Active, not recruiting
North Carolina Retina Associates
Wake Forest, North Carolina, 27587
- Active, not recruiting
Bay Area Retina Associates
Walnut Creek, California, 94598
- Active, not recruiting
Eye Clinic of Wisconsin
Wausau, Wisconsin, 54403
- Active, not recruiting
Palmetto Retina Center
West Columbia, South Carolina, 29169
- Active, not recruiting
Haik Humble Eye Center
West Monroe, Louisiana, 71291
- Active, not recruiting
Vitreoretinal Consultants of NY
Westbury, New York, 11590
- Active, not recruiting
Strategic Clinical Research
Willow Park, Texas, 76087
Argentina11 sites
- Active, not recruiting
Hospital Britanico de Buenos Aires
Buenos Aires, 1008
- Active, not recruiting
Centro Privado de Ojos
Buenos Aires, 1033
- Active, not recruiting
Charles Research Center
Buenos Aires, 1116
- Active, not recruiting
OFTALMOS
Buenos Aires, 1830
- Active, not recruiting
Centro Privado de Ojos Romagosa
Córdoba, Córdoba Province, 50000
- Active, not recruiting
IMOC
Córdoba, Córdoba Province, 5000
- Active, not recruiting
Centrovisión
Mendoza, 5500
- Active, not recruiting
Grupo Láser Visión
Rosario, Santa Fe Province, 2000
- Active, not recruiting
Microcirugia Ocular Rosario
Rosario, Santa Fe Province, 2000
- Active, not recruiting
Centro de la Vision
Salta, 4400
- Active, not recruiting
IZBA Inv Clinica
Salta, 4400
Japan11 sites, 11 recruiting
- Recruiting
Toho University Medical Center Sakura Hospital
Chiba, Sakura-shi, 285-8741
Fumihiko Yagi
- Recruiting
Social Medical Corporation Foundation Chiyuukai Fukuoka Wajiro Hospital
Fukuoka, 811-0213
Koji Murata, MD
- Recruiting
Kyushu University Hospital
Fukuoka, 812-8582
Satomi Shiose
- Recruiting
Hayashi Eye Hospital
Fukuoka
Ken Hayashi, MD, PhD
- Recruiting
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1295
Ryo Mukai
- Recruiting
University of the Ryukyus Hospital
Ginowan, Okinawa, 901-2725
Hideki Koizumi, MD, PhD
- Recruiting
Hyogo Prefectural Amagasaki General Medical Center
Hyōgo, Amagasaki-Shi, 660-8550
Hideyasu Oh
- Recruiting
Kozawa Eye Hospital and Diabetes Center
Mito, Ibaraki, 310-0845
Genichiro Kishino, MD
- Recruiting
University of Miyazaki Hospital
Miyazaki, Miyazaki, 889-1692
Yasuhiro Ikeda
- Recruiting
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
Koji Nishiguchi
- Recruiting
National Hospital Organization Tokyo Medical Center
Tokyo, 152-8902
Kunihiko Akiyama, MD, PhD
Israel8 sites
- Active, not recruiting
Rambam Health Care Campus
Haifa, 31096
- Active, not recruiting
Carmel Medical Center
Haifa, 3434104
- Active, not recruiting
Wolfson Medical Center
Holon, 5822012
- Active, not recruiting
Shaare Zedek Medical Center
Jerusalem, 9103102
- Active, not recruiting
Hadassah Medical Center Ein-Kerem
Jerusalem, 911200
- Active, not recruiting
Sheba Medical Center
Ramat Gan, 5266202
- Active, not recruiting
Kaplan Medical Center
Rehovot, 7661041
- Active, not recruiting
Tel Aviv Medical Center
Tel Aviv, 6423906
Hungary6 sites
- Active, not recruiting
Bajcsy-Zsilinszky Kórház
Budapest, 1106
- Active, not recruiting
Budapest Retina Associates
Budapest
- Active, not recruiting
Semmelweis Egyetem - Szemészeti Klinika
Budapest
- Active, not recruiting
DE KK Ophthalmology Clinic
Debrecen
- Active, not recruiting
Ganglion Medical Center
Pécs
- Active, not recruiting
SzTE SZAKK Szemeszeti Klinika
Szeged
Australia4 sites
- Active, not recruiting
Adelaide Eye and Retina Centre
Adelaide, SA 5000
- Active, not recruiting
Eye Clinic Albury Wodonga
Albury, NSW 2640
- Active, not recruiting
Strathfield Retina Clinic
Strathfield, NSW 2135
- Active, not recruiting
Sydney Retina Clinic and Day Surgery
Sydney, NSW 2000
South Korea4 sites
- Active, not recruiting
Yeungnam University Medical Center
Daegu, 42415
- Active, not recruiting
Pusan National University Hospital
Seogu, Busan, 49241
- Active, not recruiting
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
- Active, not recruiting
Kyung Hee University Hospital
Seoul, Dongdaemun District, 2447
France3 sites
- Active, not recruiting
Centre Paradis Monticelli
Marseille, 13008
- Active, not recruiting
Clinique Jules Verne
Nantes, 44300
- Active, not recruiting
CHU de Nice - Hopital Pasteur 2
Nice, PACA, 06001
Germany3 sites
- Active, not recruiting
Internationale Innovative Ophthalmochirurgie GbR
Düsseldorf
- Active, not recruiting
Augenzentrum Frankfurt
Frankfurt, 60549
- Active, not recruiting
Dietrich Bonhoeffer Klinikum
Neubrandenburg, 17036
Latvia3 sites
- Active, not recruiting
P.Stradins University Hospital
Riga
- Active, not recruiting
Riga East University hospital
Riga
- Active, not recruiting
Ziemekurzemes Regionala Slimnica
Ventspils
Spain3 sites
- Active, not recruiting
Clinica Bonanova de Cirugía Ocular
Barcelona
- Active, not recruiting
Miranza Instituto Gomez-Ulla
Santiago de Compostela, 15706
- Active, not recruiting
Hospital Universitario Virgen Macarena
Seville
United Kingdom3 sites
- Active, not recruiting
Bradford Royal Infirmary
Bradford, UK, BD9 6TB
- Active, not recruiting
The Retina Clinic London
London
- Active, not recruiting
Sunderland Eye Infirmary
Sunderland, SR2 9HP
Lithuania2 sites
- Active, not recruiting
Hospital of Lithuanian University of Health Sciences
Kaunas, LT-50161
- Active, not recruiting
Vilnius University Hospital Santaros Klinikos
Vilnius
Singapore2 sites
- Active, not recruiting
Singapore Eye Research Institute (SERI)
Singapore
- Active, not recruiting
Tan Tock Seng Hospital TTSH
Singapore
About this study
Official title: A Phase 3, Randomized, Double-Masked, Active-Controlled Trial of a Single Intravitreal Injection of 4D-150 in Adults With Macular Neovascularization Secondary to Age-Related Macular Degeneration
This Phase 3 study is evaluating the safety and efficacy of 4D-150 versus aflibercept in participants with neovascular age-related macular degeneration (nAMD). Enrollment in the primary global cohort has been completed; Study centers in Japan remain open for enrollment for the Japan cohort.
- Being tested
- 4D-150 IVT (3E10 vg/eye), EYLEA® (aflibercept) Injection 2 mg (0.05mL)
- Keywords
- Age-related macular degeneration, AMD, Exudative AMD, Neovascular AMD, Exudative age-related macular degeneration, Neovascular age-related macular degeneration, Wet age-related macular degeneration, Wet macular degeneration, Wet AMD, WAMD, nAMD, Retinal gene therapy, Intravitreal gene therapy, Genetic Medicine, Ocular Gene Therapy, Gene Therapy, 4FRONT, 4FRONT-2
- Medical subject headings
- Macular Degeneration, Wet Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-150 IVT (3E10 vg/eye)Biological
If randomized to the 4D-150 treatment arm, 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1
EYLEA® (aflibercept) Injection 2 mg (0.05mL)Biological
Eylea (aflibercept) will be administered at applicable visits
| Study group | Role | What they receive |
|---|---|---|
| 4D-150 IVT (3E10 vg/eye) | Experimental | Not described Receives: Biological: 4D-150 IVT (3E10 vg/eye) |
| Aflibercept (AFLB) 2 mg IVT | Active comparator | Not described Receives: Biological: EYLEA® (aflibercept) Injection 2 mg (0.05mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change from baseline in Best Corrected Visual Acuity (BCVA) Early Treatment for Diabetic Retinopathy (ETDRS) letter score at Week 52
Measured: 52 Weeks
Secondary outcomes (5)
Mean annualized number of aflibercept injections after Week 4 through Weeks 52 and 104
Measured: 104 Weeks
Incidence and timing of aflibercept injections after Week 4 through Weeks 52 and 104
Measured: 104 Weeks
Proportion of subjects not requiring aflibercept injections after Week 4 through Weeks 52 and 104 in the 4D-150 arm
Measured: 104 Weeks
Mean change from baseline in Central Subfield Thickness (CST) over time through Weeks 52 and 104
Measured: 104 Weeks
Mean change from baseline in BCVA ETDRS letter score over time through Weeks 52 and 104
Measured: 104 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2025
- Study start22 Jul 2025
- Primary completionNov 2027 (estimated)
- Study completionNov 2029 (estimated)
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 Degeneration (nAMD)Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 4D Molecular Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julie Tsai, MD, Study director, 4D Molecular Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07064759
- Sponsor's protocol ID
- 4D-150-C004
- Acronym
- 4FRONT-2
- Status last verified
- Oct 2026
- First submitted
- 7 Jul 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data obtained through this study may be provided, after deidentification, to qualified researchers with academic interest in AMD in compliance with ICMJE policy. Data or samples shared will be coded, with no Protected Health Information included. Additionally, descriptions of the study protocol, Statistical Analysis Plan (SAP), informed consent and clinical study report may be shared publicly. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party. Data requests can be submitted starting after final Clinical Study Report and the data will be made accessible for a duration determined by the Sponsor, and in accordance with ICMJE policy. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and SAP and execution of a Data Sharing Agreement (DSA).