Efficacy Evaluation Study of BAT5906 and Lucentis® in Patients With Diabetic Macular Edema

A Multicenter, Randomized, Double-Blind Phase III Clinical Study Comparing the Efficacy and Safety of BAT5906 Versus Ranibizumab (Lucentis®) in Patients With Diabetic Macular Edema (DME)

A multicenter, randomized, double-blind, parallel-group, active-controlled non-inferiority trial. A total of 406 subjects with diabetic macular edema (DME) were planned for enrollment. After screening, eligible subjects were randomized in a 1:1 ratio to the treatment group or the control group. The treatment group received BAT5906 injection, while the control group received Lucentis®. During the trial, ophthalmic examinations and safety assessments were conducted according to the protocol for efficacy and safety evaluation. Blood samples were collected for immunogenicity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in the study eye from baseline to week 52 (measured using the ETDRS chart).

Inclusion Criteria:

• All of the following criteria must be met for inclusion:

  1. Voluntarily signed informed consent form, willing and able to comply with outpatient visits and study procedures as scheduled by the trial.
  2. Diagnosed with type 1 or type 2 diabetes, aged 18 to 80 years (including boundary values).
  3. Diabetic macular edema (DME) with OCT findings demonstrating involvement of the macular center (fovea or paracentral fovea) in the study eye. (fovea or parafovea);
  4. Central retinal thickness (CRT) of the study eye >300 μm (or >320 μm for Heidelberg OCT) as assessed by central image review during screening;
  5. Best-corrected visual acuity (BCVA) of the study eye between 73 and 21 letters (using ETDRS chart, including boundary values; equivalent to Snellen visual acuity scores of 20/40 to 20/400);
  6. Contralateral eye BCVA > 24 letters (using ETDRS chart, equivalent to Snellen acuity 20/320); Note: If both eyes meet inclusion criteria, the eye with poorer BCVA is selected as the study eye, unless the investigator determines the other eye is more suitable.

Exclusion Criteria:

• Patients meeting any of the following criteria will be excluded from this study:

  1. Presence of structural damage in the central macula of the study eye that may prevent improvement in best-corrected visual acuity after resolution of macular edema, including retinal pigment epithelial cell atrophy, subretinal fibrosis or scarring, significant macular ischemia (as indicated by marked disruption of the arcade pattern on fluorescein angiography), or histochemical sclerosing exudates. 2. Vitreomacular traction or epimacular membrane deemed by the investigator to significantly impair visual improvement;

  2. Presence of any condition in the study eye other than diabetic macular edema that may confound fundus evaluation or visual acuity testing (e.g., retinal vascular occlusion, retinal detachment, optic nerve ischemia, vitreomacular traction, macular hole, pre-retinal fibrosis involving the macula, choroidal neovascularization, age-related macular degeneration);

  3. Aphakia in the study eye or presence of an intraocular lens with posterior capsule opacification (exemption granted for posterior capsule opacification resulting from YAG capsulotomy, provided a 1-month washout period is met);

  4. The study eye has uncontrolled glaucoma (intraocular pressure >25 mmHg despite antiglaucoma medication); or a history of glaucoma filtration surgery; or plans for antiglaucoma surgery during the study period;

  5. The study eye has undergone vitreoretinal surgery or scleral buckling;

  6. The study eye has undergone panretinal photocoagulation (PRP) or focal/grid PRP in the macular area within the preceding 3 months, or there is a possibility of undergoing PRP during the study period;

  7. Presence of neovascular glaucoma, iris neovascularization, or other clinically significant iris lesions deemed abnormal by the investigator in the study eye;

  8. Active proliferative diabetic retinopathy (PDR) in the study eye, characterized by fibrovascular proliferation, vitreous hemorrhage, and retinal detachment;

  9. The study eye has undergone intraocular surgery within the past 3 months, or is scheduled to undergo intraocular surgery during the study period;

  10. The study eye has refractive media opacities (e.g., corneal scarring, undilatable pupils, cataracts, vitreous hemorrhage) that interfere with visual acuity assessment or fundus examination;

  11. The study eye has received intravitreal injection of long-acting or sustained-release corticosteroids (e.g., dexamethasone intravitreal implant) or high-dose oral corticosteroids (>10 mg prednisolone or equivalent daily dose) within 6 months prior to baseline, except for patients using inhaled, intranasal, or low-dose topical corticosteroids applied to the skin; the study eye had received intravitreal injections of short- or medium-acting corticosteroids (e.g., triamcinolone) within 3 months prior to baseline; Periorbital corticosteroid injections administered to the study eye within 1 month prior to baseline; Fluocortolone intravitreal implants used in the study eye at any time prior to baseline; Systemic corticosteroid therapy received within 5 days prior to baseline;

  12. The equivalent spherical refractive error of the study eye exceeds -6.0 diopters. For patients with a history of refractive or cataract surgery, the refractive error of the study eye should not exceed -6.0 diopters preoperatively. If preoperative refractive results are unavailable, the measured axial length must not exceed 26mm;

  13. History of uveitis in either eye;

  14. Active ocular inflammation or infection (bacterial, viral, parasitic, or fungal) in either eye;

  15. Receipt of anti-VEGF therapy in the study eye or systemic administration within 90 days (inclusive) prior to randomization;

      Exclusion Criteria for Abnormal Laboratory Findings:

  16. Abnormal liver or renal function (defined in this trial as ALT and AST not exceeding 2.5 times the upper limit of normal for this center's laboratory; Crea and BUN not exceeding 2 times the upper limit of normal for this center's laboratory);

  17. Coagulation abnormalities (prothrombin time > 3 seconds above the upper limit of normal, activated partial thromboplastin time > 10 seconds above the upper limit of normal);

  18. Patients with any active infection: positive hepatitis B screening (defined as positive hepatitis B surface antigen and HBV-DNA > 1000 IU/mL or the hospital's maximum cutoff value), Positive screening for hepatitis C (defined as positive HCV antibodies and positive HCV-RNA), positive human immunodeficiency virus (HIV) antibodies, positive screening for Treponema pallidum antibodies (Anti-TP) (positive specific antibody test, negative non-specific antibody test, except for those clinically assessed as non-active infection).

      Other exclusion criteria:

  19. Acute cardiovascular or cerebrovascular disease, related treatment, or other thromboembolic disorders within 6 months prior to first dosing;

  20. Poorly controlled diabetes or glycated hemoglobin (HbA1c) >11%;

  21. Uncontrolled hypertension (defined as blood pressure >160/95 mmHg despite antihypertensive medication);

  22. Undergone surgery within the past month with unhealed wounds, or as determined by the investigator;

  23. Diagnosed systemic autoimmune disease (e.g., ankylosing spondylitis, systemic lupus erythematosus) or any uncontrolled clinical condition (e.g., malignancy, active hepatitis, severe psychiatric, neurological, cardiovascular, respiratory disorders);

  24. History of conditions contraindicated for the study drug, metabolic dysfunction, physical examination findings, or diseases/symptoms reasonably suspected based on clinical laboratory results that are contraindications for the study drug, may affect study outcome assessment, or expose the subject to a higher risk of complications;

  25. Known allergy or contraindication to the study drug or its components, fluorescein, povidone-iodine, or indocyanine green;

  26. Participation in any drug clinical trial (excluding vitamins and minerals) within 90 days prior to the first study dose (calculated from the last dose of the investigational drug; if the investigational drug has a long half-life, the period shall be 5 half-lives if >3 months);

  27. Pregnant, pregnant women, or lactating women (pregnancy defined in this trial as a positive blood/urine pregnancy test); Male or female subjects of reproductive potential who refuse to use appropriate contraception (e.g., intrauterine device, oral contraceptives, condoms) throughout the study period and for 3 months after the last visit. Women defined as reproductive potential include those who have not yet reached menopause, or who have reached menopause but have not maintained a continuous menopausal state for >12 months, and who have not undergone sterilization (ovariectomy and/or hysterectomy). The definition of fertility may be adjusted according to local standards in each region.

      Note: Highly effective contraceptive methods include complete abstinence, intrauterine devices, dual barrier methods (e.g., condom + spermicide-containing diaphragm), contraceptive implants, hormonal contraceptives [oral contraceptives, contraceptive implants, transdermal patches, hormonal vaginal devices, or depot injections], or a partner who has undergone vasectomy with confirmed azoospermia.

  28. Other conditions deemed by the investigator to warrant exclusion.