This study will demonstrate that tarcocimab 5 mg is superior to sham treatment in participants with DR.

This is a prospective, randomized, double-masked, two-arm, multi-center Phase 3 study to demonstrate that tarcocimab 5 mg is superior to sham treatment, with respect to the proportion of eyes improving from baseline at Week 48 in participants with DR.

Inclusion Criteria:

• Signed informed consent prior to participation in the study.
• Type 1 or 2 diabetes mellitus and HbA1c of ≤12%.
• DR in the Study Eye (DRSS as determined by the reading center based on color fundus photographs), who have not previously received intravitreal medications for DR or DME, and in whom pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
• CST ≤320 microns and a BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better) in the Study Eye at screening and confirmed at Day 1; OR
• CST >320 and ≤350 microns and a BCVA ETDRS letter score in the Study Eye of ≥79 letters (approximate Snellen equivalent of 20/25 or better) in the Study Eye at screening and confirmed at Day 1.

Exclusion Criteria:

• Prior PRP in the Study Eye.
• Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
• Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME within the last twelve (12) months prior to Day 1.
• Prior intravitreal or periocular steroid in the Study Eye for DR or DME within the last twelve (12) months prior to Day 1.
• Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
• History of vitreoretinal surgery in the Study Eye.
• History of uveitis in either eye.
• Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening.
• Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT, or FP.
• Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study.
• Active or suspected ocular or periocular infection or inflammation.
• Women who are pregnant or lactating or intending to become pregnant during the study.
• History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
• Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
• Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest.
• Other protocol-specified exclusion criteria may apply.

To preserve masking, 2 investigators are required for this study. The masked investigator will be responsible for examinations and safety assessments. The unmasked investigator will perform the injections and post-treatment assessments.