Diabetic Macular Edema (DME)Phase 34SIGHTNCT07867080
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
A Phase 3 study testing 4D-150 IVT (3x10^10 vg) and EYELEA ® (aflibercept) Injection 2 mg (0.05mL) in people with Diabetic Macular Edema (DME), run by 4D Molecular Therapeutics at 82 sites in 3 countries.
Trial summary
A Phase 3, Randomized, Double-Masked, Active-Controlled Trial to Evaluate the Safety, Efficacy, and Durability of a Single Intravitreal Injection of 4D-150 versus Aflibercept in Adults with Diabetic Macular Edema (4SIGHT) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema (DME)
- What is being tested?
- 4D-150 IVT (3x10^10 vg) and EYELEA ® (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
- 514 participants
- Where
- 82 sitesin 3 countries
- Study dates
- 18 Sep 2026to Jan 2030
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
5.2 Inclusion Criteria
Individuals eligible to participate in the trial must meet the following inclusion criteria:
General Inclusion Criteria
- Signed informed consent before any protocol-specified assessment is performed
- Ability and willingness to comply with the protocol-specified procedures (including IVT injection) and visits, in the Investigator's judgment
- ≥18 years of age at time of signing informed consent
- Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
- WOCBP must agree to use highly effective contraception from the time of informed consent, through duration of trial participation
- Agree to use a barrier method (e.g., condom) during intercourse for 3 months after Day 1 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period Ocular Inclusion Criteria
- Macular thickening secondary to DME involving the center of the fovea (confirmed by the Reading Center) in the study eye
- Study eye amenable to IVT injection identified
- Presence of intraretinal fluid and/or subretinal fluid secondary to DME
- Decreased visual acuity attributable primarily to DME, as determined by the Investigator
- Demonstrated clinical response to aflibercept and functional stability in the study eye
Exclusion Criteria: Individuals who meet any of the following exclusion criteria will not be eligible to participate:
Ocular Condition
- Macular conditions other than DME
- History or presence of moderate Proliferative Diabetic Retinopathy or worse
- History of retinal detachment in the study eye
- History or presence of active inflammation or infection in either eye
- History or presence of low Intraocular Pressure
- Uncontrolled glaucoma or intraocular hypertension Ocular Treatments/Interventions:
- Any prior concomitant treatment for DME
- History of prior significant ocular surgery or treatment
- Any prior investigational drug, agent, device, or gene therapy
Trial locations and contacts
82 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
4SIGHT Medical Monitoring Distribution List contact
82 sites in 3 countries
United States49 sites, 49 recruiting
- Not yet recruiting
West Texas Retina Consultants
Abilene, Texas, 79606
- Not yet recruiting
Asheville Eye Associates - Retina Division
Asheville, North Carolina, 28803
- Recruiting
Retina Specialists of Colorado - Aurora
Aurora, Colorado, 80012
- Recruiting
Austin Clinical Research
Austin, Texas, 78750
- Not yet recruiting
Mid Atlantic Retina
Bethlehem, Pennsylvania, 18017
- Not yet recruiting
Envision Ocular, LLC
Bloomfield, New Jersey, 07003
- Not yet recruiting
Midwest Eye Institute
Carmel, Indiana, 46032
- Not yet recruiting
The Retina Group of Washington
Chevy Chase, Maryland, 20815
- Not yet recruiting
Retina Consultants of Southern Colorado P.C.
Colorado Springs, Colorado, 80909
- Not yet recruiting
Texas Retina Associate
Dallas, Texas, 75231
- Not yet recruiting
Southwest Retina Consultants
Durango, Colorado, 81303
- Not yet recruiting
NJ Retina
Edison, New Jersey, 08820
- Not yet recruiting
Retina Vitreous Center
Edmund, Oklahoma, 73013
- Recruiting
Retina Associates, Ltd.
Elmhurst, Illinois, 60126
- Recruiting
The Retina Partners
Encino, California, 91436
- Not yet recruiting
The Retina Group of Washington
Fairfax, Virginia, 22031
- Not yet recruiting
Retina Consultants of Orange County
Fullerton, California, 92835
- Not yet recruiting
Coastal Eye- Greenwich
Greenwich, Connecticut, 06830
- Not yet recruiting
Cumberland Valley Retina Consultants
Hagerstown, Maryland, 21740
- Not yet recruiting
Mid Atlantic Retina Specialist
Hagerstown, Maryland, 21740
- Recruiting
Texas Retina Center
Houston, Texas, 77030
- Not yet recruiting
Retina Consultants of Texas - Katy
Katy, Texas, 77494
- Not yet recruiting
Piedmont Eye Center
Lynchburg, Virginia, 24502
- Not yet recruiting
Mississippi Retina Associates
Madison, Mississippi, 39110
- Not yet recruiting
NYU Langone Health
New York, New York, 10017
- Not yet recruiting
Retina Vitreous Surgeons of CNY, PC
New York, New York, 13088
- Not yet recruiting
University Retina and Macula Associates
Oak Forest, Illinois, 60452
- Not yet recruiting
Illinois Retina Associates
Oak Park, Illinois, 60304
- Not yet recruiting
Florida Retina Institute
Orlando, Florida, 32806
- Recruiting
Retinal Specialty Institute
Pensacola, Florida, 32503
- Not yet recruiting
Fort Lauderdale Eye Institute (FLEI)-Plantation
Plantation, Florida, 33324
- Not yet recruiting
EyeHealth Northwest
Portland, Oregon, 97233
- Not yet recruiting
Black Hills Regional Eye Institute
Rapid City, South Dakota, 57701
- Recruiting
Sierra Eye Associates
Reno, Nevada, 89502
- Not yet recruiting
Retinal Consultants Medical Group Inc.
Sacramento, California, 95825
- Not yet recruiting
Retina Consultants San Diego
San Diego, California, 92064
- Not yet recruiting
Retina Institute of New England
San Mateo, California, 94401
- Recruiting
Research Network Arizona
Scottsdale, Arizona, 85255
- Not yet recruiting
Deep Blue Retina Clinical Research, PLLC
Southaven, Mississippi, 38671
- Not yet recruiting
Springfield Clinic
Springfield, Illinois, 62703
- Not yet recruiting
The Retina Institute
St Louis, Missouri, 63128
- Recruiting
Retina Vitreous Associates of Florida
Tampa, Florida, 33607
- Not yet recruiting
Retina Consultants of Texas
The Woodlands, Texas, 77384
- Not yet recruiting
Tyler Retina Consultants
Tyler, Texas, 75703
- Not yet recruiting
North Carolina Retina Associates- Wake Forest
Wake Forest, North Carolina, 27587
- Not yet recruiting
Bay Area Retina Associates - Walnut Creek
Walnut Creek, California, 94598
- Not yet recruiting
Retina Institute of New England, PC
Waterford, Connecticut, 06385
- Not yet recruiting
Eye Clinic of Wisconsin
Wausau, Wisconsin, 55403
- Not yet recruiting
Vitreoretinal Consultants of New York (VRCNY)
Westbury, New York, 11590
China18 sites, 18 recruiting
- Not yet recruiting
Beijing Tongren Hospital
Beijing, 100730
- Not yet recruiting
The Second Hospital of Jilin University
Changchun, 130041
- Not yet recruiting
The Second Xiangya Hospital of Central South University
Changsha, 410300
- Not yet recruiting
The Second Affiliated Hospital of Harbin Medical University
Haerbin, 150001
- Not yet recruiting
Zhejiang Provincial People's Hospital
Hangzhou, 310015
- Not yet recruiting
Eye Hospital of Shandong First Medical University
Jinan, 250021
- Not yet recruiting
Zhengzhou Second Peoples Hospital
Jinan, 450006
- Not yet recruiting
Lanzhou University Second Hospital
Lanzhou, 730030
- Not yet recruiting
Nanchang University Affiliated Eye Hospital
Nanchang, 330006
- Not yet recruiting
Fudan University - Eye & ENT Hospital
Shanghai, 200031
- Not yet recruiting
Shanghai First People's Hospital
Shanghai, 200080
- Not yet recruiting
Shanxi Academy of Medical Sciences - Shanxi Bethune Hospital
Taiyuan, 030032
- Not yet recruiting
Taizhou Hospital of Zhejiang Province
Taizhou, 317000
- Not yet recruiting
Tianjin Medical University Eye Hospital
Tianjin, 300384
- Not yet recruiting
Weifang Eye Hospital
Weifang, 261021
- Not yet recruiting
Huazhong University of Science and Technology-Tongji Medical College-The Central Hospital of Wuhan
Wuhan, 430014
- Not yet recruiting
Wuhan University Renmin Hospital (Hubei General Hospital)
Wuhan, 430060
- Not yet recruiting
Henan Eye Hospital, Henan Provincial People's Hospital
Zhengzhou, 450003
Japan15 sites, 15 recruiting
- Not yet recruiting
Hyogo Prefectural Amagasaki General Medical Center (Hyogo AGMC)
Amagasaki-shi, 660-8550
- Not yet recruiting
Hayashi Eye Hospital
Fukuoka, 812-0011
- Not yet recruiting
Kyushu University Hospital
Fukuoka, 812-8582
- Not yet recruiting
Fukushima Medical University Hospital
Fukushima, 960-1295
- Not yet recruiting
Tokyo Medical University Hachioji Medical Center
Hachioji-shi, 193-0998
- Not yet recruiting
Kagoshima University Hospital
Kagoshima, 890-8520
- Not yet recruiting
Kagawa University Hospital
Kita-Gun, 761-0793
- Not yet recruiting
Kobe City Eye Hospital
Kobe, 650-0047
- Not yet recruiting
Kyoto University Hospital
Kyoto, 606-8507
- Not yet recruiting
Kozawa Eye Hospital and Diabetes Center
Mito, Ibaraki, 310-0845
- Not yet recruiting
University of Miyazaki Hospital
Miyazaki, 889-1692
- Not yet recruiting
Nagoya University Hospital
Nagoya, 466-8560
- Not yet recruiting
Toho University Sakura Medical Center
Sakura-shi, 285-8741
- Not yet recruiting
Juntendo University Hospital
Tokyo, 113-8431
- Not yet recruiting
National Hospital Organization Tokyo Medical Center
Tokyo, 152-8902
About this study
Official title: A Phase 3, Randomized, Double-Masked, Active-Controlled Trial to Evaluate the Efficacy, Safety, and Durability of a Single Intravitreal Injection of 4D-150 Versus Aflibercept in Adults With Diabetic Macular Edema (4SIGHT)
A Phase 3, Randomized, Double-Masked, Active-Controlled Trial to Evaluate the Safety, Efficacy, and Durability of a Single Intravitreal Injection of 4D-150 versus Aflibercept in Adults with Diabetic Macular Edema (4SIGHT)
- Conditions
- Diabetic Macular Edema (DME)
- Being tested
- 4D-150 IVT (3x10^10 vg), EYELEA ® (aflibercept) Injection 2 mg (0.05mL)
- Keywords
- Diabetic Macular Edema, DME, Retinal gene therapy, Intravitreal gene therapy, Genetic Medicine, Ocular Gene Therapy, Eye Diseases, Intravitreal Injections, Aflibercept
- Medical subject headings
- Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-150 IVT (3x10^10 vg)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
EYELEA ® (aflibercept) Injection 2 mg (0.05mL)Biological
EYLEA ® (aflibercept) will be administered at applicable visits
| Study group | Role | What they receive |
|---|---|---|
| 4D-150 IVT (3x10^10 vg/eye) | Experimental | Not described Receives: Biological: 4D-150 IVT (3x10^10 vg) |
| Active Comparator (AFLB) 2mg IVT | Active comparator | Not described Receives: Biological: EYELEA ® (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 Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letter score at Week 52
The minimum and maximum values are: 0 to 100 The higher the value the better the result
Measured: 52 weeks
Secondary outcomes (2)
Mean annualized number of aflibercept injections after Week 4 through Week 52
Minimum 0 maximum 12 One injection per visit, one visit every four weeks
Measured: Week 4 through Week 52
Proportion of participants with a ≥ 2-step improvement from baseline in Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52
ETDRS-DRSS is a visual acuity test Results are analyzing using a generalized estimating equations model
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2026
- Study start18 Sep 2026
- Primary completionJan 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Macular Edema (DME)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
- 514 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 4D Molecular Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07867080
- Sponsor's protocol ID
- 4D-150-C005
- Other IDs
- 4SIGHT, 4D-150-C005
- Acronym
- 4SIGHT
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2026
- Last updated
- 13 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 DME 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)