Efficacy Evaluation Study of BAT5906 and Lucentis® in Patients With Macular Degeneration
Study Details
Study Description
Brief Summary
A multicenter study of randomized, double-blind, and parallel control of positive drugs was conducted using a non-inferior design. Eligible neovascular (wet) age-related macular degeneration (w-AMD) subjects were screened into a trial group and a control group, with the test group receiving BAT5906 injection and the control group treated with Lucentis®.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
A multicenter study of randomized, double-blind, and parallel control of positive drugs was conducted using a non-inferior design. 488 neovascular (wet) age-related macular degeneration (w-AMD) subjects were selected, and the qualified subjects were selected in a 1:1 ratio divided into experimental and control groups, and the baseline period letter values and whether the study eye had received anti-VEGF drug treatment were randomized in stratification, the experimental group received BAT5906 injection and the control group received Lucentis®. Only 1 eye per participant was selected for this study.
The dosing regimen is: 4 mg of BAT5906 or 0.5 mg of Lucentis® intravitreally every 4 weeks, the treatment period during the study period is 48 weeks, a total of 13 doses, the last follow-up at week 52, the last visit without treatment, only effectiveness, safety assessment, and blood samples are collected as required.
During the test, the subjects are subjected to eye examination, vital signs, physical examination, laboratory tests for effectiveness and safety assessment according to the test procedure specified in the program, and blood samples are collected to detect immunogenicity indicators. The ETDRS eye chart was used to evaluate the change in the best corrected vision from baseline to baseline, with the main efficacy index being the change in the target eye's optimal corrected vision (BCVA) from baseline at 52 weeks, and the secondary efficacy measures being the baseline change in the target eye's optimal corrected vision (BCVA) at 12, 24, 36 weeks, and 48 weeks, and the change in macular fovea thickness (CRT) from baseline.
Blood samples are taken at the time point specified in the protocol, the serum antibiotic antibodies (ADA) are detected, and the samples that confirm positive ADA are subjected to titer analysis and neutralizing antibody (Nab) analysis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental group：BAT5906 Intravitreal injection; Dosage: 4.0 mg / eye / time, 50 μl; Duration of administration: every 4 weeks, administered to week 48, not administered at 52 weeks. |
Drug: BAT5906 injection
4.0 mg/eye/time, 50 μl, intravitreal injection
|
| Active Comparator: Control group：Lucentis® Intravitreal injection; Dosage: 0.5 mg / eye / time, 50 μl; Duration of administration: every 4 weeks, administered to week 48, not administered at 52 weeks. |
Drug: Lucentis
0.5 mg/eye/time, 50 μl, intravitreal injection
|
Outcome Measures
Primary Outcome Measures
- The change in the BCVA value [Week 52]
Compared to baseline, two groups of subjects studied the value of changes in ocular 52nd week BCVA
- The change in the BCVA value [at weeks 12, 24, 36, and 48]
Compared to baseline, two groups of subjects studied the changes in bcVA at weeks 12, 24, 36, and 48 of the eye
- BCVA increased the proportion of subjects with >10, >15, ≥30 words [in the 24th and 52nd weeks]
Compared with baseline, the proportion of subjects with 30 words of BCVA in the 24th and 52nd weeks of the study eye was improved > 10, >15, ≥ 30 words;
- BCVA reduced the proportion of subjects < 10, < 15 words [at weeks 24 and 52]
Compared with baseline, the proportion of subjects in both groups who studied eye bcVA at weeks 24 and 52 decreased <10, < 15 words
- Changes in the thickness of the macular fovea (CRT). [at weeks 12, 24, 36, 48, and 52]
Changes in the thickness of the macular fovea (CRT) at weeks 12, 24, 36, 48, and 52 were studied in both groups of subjects compared to baseline
Secondary Outcome Measures
- Vital signs [Weeks 1 to 52]
Number of participants with abnormal vital signs
- physical examination [Weeks 1 to 52]
Number of participants with abnormal physical examination findings
- Laboratory tests [Weeks 1 to 52]
Number of participants with abnormal laboratory test results
- electrocardiogram（ ECG ） [Weeks 1 to 52]
Number of participants with abnormal ECG readings
- Antibiotic antibodies (ADA) [Weeks 1 to 52]
Resistance antibody (ADA) situation in the subject
- Adverse events（AE） [Weeks 1 to 52]
Ocular and non-ocular adverse events (AE) and serious adverse events (SAE)
- Adverse events of particular concern (possible adverse reactions to the eye) [Weeks 1 to 52]
Endophthalmia, increased intraocular pressure, subconjunctival hemorrhage, ocular foreign body sensation, visual impairment, corneal abrasions, lens damage, retinal detachment, retinal artery occlusion, etc.; Possible systemic adverse effects include non-ocular bleeding, increased blood pressure, and thromboembolic events
Other Outcome Measures
- Immunogenicity evaluation [Weeks 1 to 52]
Blood samples from BAT5906 and Lucentis® injections were detected for ADA detection and analysis to detect anti-BAT5906 antibodies (ADA). Serum antibodies (ADA) are tested, and neutralizing antibody (Nab) analysis will continue if the ADA is confirmed positive.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Understand and sign an informed consent form and be willing to follow up according to the time specified in the trial;
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Age 50-85 years old (including boundary values), male or female;
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Study subjects with confirmed neoovascular age-related macular degeneration and imaging examination confirm that there are still active lesions. Active lesions are defined as the presence of any of the following lesions in the macular area: (1) intraretinal fluid; (2) Lipid exudation in the retina; (3) subretinal fluid; (4) Subretinal hemorrhage; (5) Detachment of the retinal pigment epithelium; (6) Choroidal neovascular leakage;
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The total area of the eye lesion was studied≤ 30mm2 (12 optic disc areas), which was confirmed by the reading center before randomization;
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The eye BCVA of the study eye is 73-19 letters at the screening and baseline (using the ETDRS vision chart, including the boundary values), which is equivalent to Snellen vision 20/40 to 20/400;
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The BCVA ≥ 19 letters detected by the ETDRS eye chart for non-study eyes screening and baseline, equivalent to Snellen vision ≥ 20/400.
Exclusion Criteria:
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Have received any intravitreal anti-VEGF treatment (e.g., bevacizumab, apercipr, rajuzumab, compaxipr, etc.) within 3 months before the study eye is randomized;
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The following treatments were received in the first 3 months of the study eye: vertepofen photodynamic therapy (PDT), laser photocoagulation in the macular area, transpupillary thermotherapy (TTT), and other surgeries for the treatment of AMD;
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The study eye has undergone the following eye surgery: vitrectomy, anti-glaucoma surgery, macular transposition. Had internal eye surgery (including cataract surgery) within 3 months prior to the study of eye randomization, or had external eye surgery within 1 month prior to randomization;
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Intravitreal injection (eg, triamcinolone acetonide, dexamethasone) within 3 months before the randomization of the eye, intravitreal injection of dexamethasone extended-release agent within 6 months, and injection of any intraocular, perocular or subconjunctival injection of long-acting corticosteroids (eg, triamcinolone acetonide, etc.) within 3 months of randomization;
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Study of ocular diseases with ocular effects on central vision (e.g., diabetic retinopathy, retinal vein occlusion, uveitis, vascular streaky changes, pathological myopia, retinal detachment, macular hiatus, anterior macular membrane, toxoplasmosis, optic nerve disease);
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Study of the eye with atrophic atrophy involving the central fovea, scarring or fibrosis, dense hard exudation of the fovea, retinal pigment epithelium (RPE) tear involving the center of the macula (confirmed by the reading center during screening);
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Study the presence of choroidal neovascularizations not caused by nAMD, progressive retinopathy that affects corrected vision, vitreous bleeding or vitreous bleeding in any eye, or history of retinal detachment;
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Equivalent spherical lenses that study ocular refractive errors show more than -6.0 diopters. For patients who have previously undergone refractive surgery or cataract surgery, the refractive error of the preoperative study eye should not exceed -6.0 diopters;
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The study eye is lensless (excluding the intraocular lens eye) or the rupture of the posterior capsule membrane of the lens (except for YAG laser posterior cystectomy after intraocular lens implantation more than 1 month from screening);
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Study the obvious refractive interstitial opacity or inability to dilate the pupils, including cataracts and corneal opacification, which may interfere with vision assessment, safety assessment or fundus photography;
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Study of pupillary afferent defect (APD) in the eye;
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Uncontrolled glaucoma in the study eye at random time, defined as intraocular pressure remaining above 25 mmHg after drug treatment, or according to the investigator's judgment;
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Non-study eye randomization received photodynamic (PDT) therapy within 1 month before;
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History of idiopathic or autoimmune-associated uveitis in any eye;
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Any eye has pseudocapsular detachment syndrome;
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Active eye infections in any eye (e.g. blepharitis, infectious conjunctivitis, keratitis, scleritis, iridocyclitis, intraocularitis);
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Systemic medications that can cause crystal toxicity or retinal toxicity, such as ferritinization, chloroquine/hydroxychloroquine, phenothiazine, and ethambutol or tamoxifen, are currently being used or may need to be used;
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Allergic reactions or allergic histories to fluorescein sodium and indocyanine green, allergies to therapeutic or diagnostic protein products, or allergic reactions to any of the monoclonal antibodies known;
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Those who had surgery within 1 month before randomization and the operation did not heal, and the researcher judged that the study drug had an effect on healing;
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The presence of clinically significant active systemic infectious diseases that are being treated;
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History of myocardial infarction, unstable angina, coronary revascularization, cerebrovascular accident (including TIA), history of other thromboembolic diseases (such as thromboembolic vasculitis, pulmonary embolism, deep vein thrombosis, portal vein thrombosis, etc.) in the first 6 months of randomization, New York Heart Association (NYHA) grade ≥ grade II cardiac insufficiency, severe unstable ventricular arrhythmia;
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Those who have active diffuse intravascular coagulation and significant bleeding tendencies (eg, hemoptysis, hematemesis, severe purpura, etc.) within the first 3 months of randomization, or who have received anticoagulant antiplatelet therapy other than aspirin/NSAIDs within 14 days before screening;
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Randomized precontrolled hypertension (defined as seated systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg after treatment with antihypertensive drugs);
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Any uncontrollable clinical problems (such as severe psychiatric, neurological, cardiovascular, respiratory and other system diseases and malignant tumors);
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Abnormal liver and kidney function (this test stipulates that ALT and AST shall not be higher than the upper limit of the normal value of the laboratory of the center by 2.5 times; Crea and BUN shall not be higher than the upper limit of the normal value of the laboratory of the center by 2 times);
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Coagulation function abnormalities (prothrombin time> upper limit of normal value of 3 seconds or activation of partial thromboplastin time > upper limit of normal value of 10 seconds);
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Patients with any of the following infections: active hepatitis B (if HBsAg(+), HBV DNA must be >1000 IU/mL), hepatitis C, AIDS, or syphilis (positive RPR test for syphilis);
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Pregnancy or lactation, or during the study period and within 6 months of the end of the study. Positive pregnancy tests during screening periods in fertile female patients;
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Subjects who have participated in any drug (excluding vitamins and minerals) in the previous 3 months of randomization and have received clinical trials of trial drugs and devices;
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The researcher does not consider it suitable for the researcher.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Bio-Thera Solutions
Investigators
- Principal Investigator: Youxin Chen, Master, Peking Union Medical College
- Principal Investigator: Xiaolin Liu, Master, Affiliated Optometry Hospital of Wenzhou Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BAT5906-004-CR