Clinical trial NCT05439629: Efficacy Evaluation Study of BAT5906 and Lucentis® in Patients With Macular Degeneration
Official title: A Multicenter, Randomized, Double-blind Phase III Clinical Study Comparing the Efficacy and Safety of BAT5906 and Ranibizumab (Lucentis®) in Patients With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neovascular (Wet) Age-related Macular Degeneration
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2022-06-30
Enrollment: 488
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A non-inferiority design was used to conduct a randomized, double-blind, parallel-controlled multi-center study. A total of 488 subjects with neovascular (wet) age-related macular degeneration (w-AMD) were planned to be enrolled. Qualified subjects were divided into experimental group and control group in a 1:1 ratio, and stratified randomized according to the letter value of baseline period and whether the eyes had received anti-VEGF drug treatment. The experimental group received BAT5906 injection. The control group received Lucentis® treatment. Only 1 eye per subject was included in this study.

Detailed description: A non-inferiority design was used to conduct a randomized, double-blind, parallel-controlled multi-center study. A total of 488 subjects with neovascular (wet) age-related macular degeneration (w-AMD) were planned to be enrolled. Qualified subjects were divided into experimental group and control group in a 1:1 ratio, and stratified randomized according to the letter value of baseline period and whether the eyes had received anti-VEGF drug treatment. The experimental group received BAT5906 injection. The control group received Lucentis® treatment. Only 1 eye per subject was included in this study.

The administration regimen was as follows: once every 4 weeks, 4mg BAT5906 or 0.5mg Lucentis® were injected intravitreal each time, the treatment period of the study was 48 weeks, a total of 13 administration times, the last follow-up was conducted at the 52nd week, the last visit did not require treatment, only efficacy and safety assessment, and blood samples were collected as required.

Ophthalmic examination, vital signs, physical examination, and laboratory examination were performed for efficacy and safety assessment according to the test procedures specified in the protocol, and blood samples were collected for immunogenicity indicators. Change in best corrected visual acuity (BCVA) from baseline was assessed by ETDRS visual acuity chart at 4-week intervals. The primary efficacy measure was the change in BCVA from baseline at 52 weeks. Secondary efficacy measures were the change in best corrected visual acuity (BCVA) of the target eye from baseline and the change in macular fovea thickness (CRT) from baseline at weeks 12, 24, 36 and 48.

Blood samples were collected according to the time points specified in the program, and the serum anti-drug antibody (ADA) was detected. Titer analysis and neutralizing antibody (Nab) analysis were performed on the samples confirmed as positive by ADA.

A non-inferiority design was used to conduct a randomized, double-blind, parallel-controlled multi-center study. A total of 488 subjects with neovascular (wet) age-related macular degeneration (w-AMD) were planned to be enrolled. Qualified subjects were divided into experimental group and control group in a 1:1 ratio, and stratified randomized according to the letter value of baseline period and whether the eyes had received anti-VEGF drug treatment. The experimental group received BAT5906 injection. The control group received Lucentis® treatment. Only 1 eye per subject was included in this study.

The administration regimen was as follows: once every 4 weeks, 4mg BAT5906 or 0.5mg Lucentis® were injected intravitreal each time, the treatment period of the study was 48 weeks, a total of 13 administration times, the last follow-up was conducted at the 52nd week, the last visit did not require treatment, only efficacy and safety assessment, and blood samples were collected as required.

Ophthalmic examination, vital signs, physical examination, and laboratory examination were performed for efficacy and safety assessment according to the test procedures specified in the protocol, and blood samples were collected for immunogenicity indicators. Change in best corrected visual acuity (BCVA) from baseline was assessed by ETDRS visual acuity chart at 4-week intervals. The primary efficacy measure was the change in BCVA from baseline at 52 weeks. Secondary efficacy measures were the change in best corrected visual acuity (BCVA) of the target eye from baseline and the change in macular fovea thickness (CRT) from baseline at weeks 12, 24, 36 and 48.

Blood samples were collected according to the time points specified in the program, and the serum anti-drug antibody (ADA) was detected. Titer analysis and neutralizing antibody (Nab) analysis were performed on the samples confirmed as positive by ADA.

Eligibility criteria: Inclusion Criteria:

1. Understand and sign the informed consent, and be willing to follow up according to the time specified in the trial;
2. Age 50-85 years old (including boundary value), male and female;
3. Study the subjects who were diagnosed with neovascular age-related macular degeneration and still had active lesions confirmed by imaging examination. Active lesions were 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) Retinal pigment epithelium detachment; ⑥ Choroidal neovascularization leakage;
4. The total area of the study eye lesions ≤30mm2(12 optic disc areas) was confirmed by the film reading center before randomization;
5. The BCVA of the study eye at screening and baseline was 73-19 letters (ETDRS visual acuity chart, including boundary values), equivalent to Snellen visual acuity 20/40 to 20/400;
6. BCVA≥19 letters, equivalent to Snellen visual acuity ≥20/400, measured by ETDRS visual chart at screening and baseline in non-study eyes.

Exclusion Criteria:

1. The study eyes received any intravitreal anti-VEGF therapy (such as bevacizumab, abbercept, ranibizumab, conbercept, etc.) within 3 months before randomization;
2. The study eyes had received the following treatments within 3 months before randomization: verteporfin photodynamic therapy (PDT), macular laser photocoagulation, transpillary thermotherapy (TTT), and other surgeries for AMD;
3. The study eyes had undergone the following ophthalmic surgeries: vitrectomy, anti-glaucoma surgery, and macular transposition. The study eyes had undergone internal eye surgery (including cataract surgery) within 3 months before randomization, or external eye surgery within 1 month before randomization;
4. The study eyes received intravitreal injection treatment (such as triamcinolone acetonide and dexamethasone) within 3 months before randomization, intravitreal injection of dexamethasone sustained release within 6 months, and injection of long-acting corticosteroids (such as triamcinolone acetonide, etc.) within, periocular or subconjunctival injection of any eye 3 months before randomization;
5. Study eyes with ocular diseases affecting central vision (such as diabetic retinopathy, retinal vein occlusion, uveitis, vascular striation, pathological myopia, retinal detachment, macular hole, macular epiretinal membrane, toxoplasmosis, optic nerve diseases);
6. Study eyes with foveal ground pattern atrophy, scar or fibrosis, dense subfoveal hard exudation, retinal pigment epithelium (RPE) tear involving the center of the macula (confirmed by the reading center during screening);
7. The study eyes had choroidal neovascularization not caused by nAMD, progressive retinopathy affecting corrected visual acuity, and any eye had vitreous hemorrhage or a history of vitreous hemorrhage, or a history of retinal detachment;
8. The equivalent spherical mirror of the study eye with refractive error showed more than -6.0 diopters. For patients with previous refractive surgery or cataract surgery, the preoperative refractive error of the study eye should not exceed -6.0 diopters;
9. The study eyes were lens free (excluding IOL eyes) or posterior lens capsule rupture (except YAG laser posterior capsuleotomy after IOL implantation more than 1 month before screening);
10. The study eye has obvious refractive interstitial opacity or pupil failure, including cataract and corneal opacity, which may interfere with visual acuity assessment, safety assessment or fundus photography;
11. The study eyes had pupil afferent defect (APD);
12. Study eyes had uncontrolled glaucoma at randomization, defined as intraocular pressure that remained higher than 25mmHg after medical treatment or as judged by the investigator;
13. Non-study eyes received photodynamic therapy (PDT) within 1 month before randomization;
14. History of idiopathic or autoimmune associated uveitis in any eye;
15. Pseudocyst stripping syndrome in any eye;
16. Active eye infection in any eye (e.g., blepharitis, infectious conjunctivitis, keratitis, scleritis, iridecocyclitis, endophthalmitis);
17. Systemic drugs that cause crystal or retinal toxicity, such as deferoxamine, chloroquine/hydroxychloroquine, phenothiazine and ethambutol or tamoxifen, are currently being used or may be required;
18. Allergic reaction or history to sodium fluorescein and indocyanine green, allergic history to protein products for therapeutic or diagnostic use, or known allergic reaction to any monoclonal antibody;
19. Patients who had surgery within 1 month before randomization and the surgery did not heal, and the investigator judged that the study drug had an effect on healing;
20. Presence of clinically significant active systemic infectious disease under treatment;
21. History of myocardial infarction, unstable angina, coronary revascularization, cerebrovascular accident (including TIA), other thromboembolic diseases (such as thromboembolic angiitis, pulmonary embolism, deep vein thrombosis, portal vein thrombosis, etc.), New York Heart Association (NYHA) grade ≥II cardiac dysfunction within 6 months before randomization, Severe unstable ventricular arrhythmias;
22. Patients with active disseminated intravascular coagulation and significant bleeding tendency (such as hemoptysis, hematemesis, severe purpura, etc.) within 3 months before randomization, or who had received anticoagulant and antiplatelet therapy other than aspirin /NSAIDs within 14 days before screening;
23. Poorly controlled hypertension before randomization (defined as sitting systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg after antihypertensive medication);
24. Any uncontrollable clinical problems (such as serious mental, neurological, cardiovascular, respiratory and other system diseases and malignant tumors);
25. Abnormal liver and kidney function (ALT and AST should not be higher than 2.5 times of the upper limit of normal value in the central laboratory; Crea and BUN shall not be higher than 2 times of the upper limit of normal value in the central laboratory);
26. Abnormal coagulation function (prothrombin time \> upper limit of normal 3 seconds or activated partial thromboplastin time \> upper limit of normal 10 seconds);
27. Patients with any of the following infections: active hepatitis B (HBV DNA \> 1000 IU/mL if HBsAg(+)), hepatitis C, AIDS, or syphilis (syphilis RPR confirmatory test positive);
28. Planned parenthood during pregnancy or lactation, or during the study period and within 6 months after the study. The pregnancy test of fertile female patients was positive during the screening period;
29. Subjects who have participated in any drug (excluding vitamins and minerals) in the clinical trial within 3 months before randomization and have been treated with the experimental drug or device;
30. The researcher believes that it is not suitable for this study.

Primary outcomes:
measure: The change in the BCVA value
timeFrame: Week 52
measure: The change in the BCVA value
timeFrame: at weeks 12, 24, 36, and 48
measure: BCVA increased the proportion of subjects with >10, >15, ≥30 words
timeFrame: in the 24th and 52nd weeks
measure: BCVA reduced the proportion of subjects < 10, < 15 words
timeFrame: at weeks 24 and 52
measure: Changes in the thickness of the macular fovea (CRT).
timeFrame: at weeks 12, 24, 36, 48, and 52
Secondary outcomes:
measure: Vital signs
timeFrame: Weeks 1 to 52
measure: physical examination
timeFrame: Weeks 1 to 52
measure: Laboratory tests
timeFrame: Weeks 1 to 52
measure: electrocardiogram（ ECG ）
timeFrame: Weeks 1 to 52
measure: Antibiotic antibodies (ADA)
timeFrame: Weeks 1 to 52
measure: Adverse events（AE）
timeFrame: Weeks 1 to 52
measure: Adverse events of particular concern (possible adverse reactions to the eye)
timeFrame: Weeks 1 to 52
Other outcomes:
measure: Immunogenicity evaluation
timeFrame: Weeks 1 to 52
Locations:
city: Beijing
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
city: Chongqing
country: China
facility: The First Affiliated Hospital of Army Medical University (Southwest Hospital)
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Fujian
country: China
facility: First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: First Affiliated Hospital, Sun Yat-Sen University
city: Guangzhou
country: China
facility: Guangzhou Aier Eye Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Ophthalmic Center, Sun Yat-sen University
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Hubei
country: China
facility: People's Hospital of Wuhan University (Hubei Provincial People's Hospital)
city: Jilin
country: China
facility: The First Hospital of Jilin University
city: Jinan
country: China
facility: Jinan Second People's Hospital
city: Jinan
country: China
facility: The Affiliated Eye Hospital of Shandong University of Chinese Medicine
city: Jinzhong
country: China
facility: Jinzhong First People's Hospital
city: Kunming
country: China
facility: The First People's Hospital of Kunming
city: Luoyang
country: China
facility: Luoyang Third People's Hospital
city: Nanchang
country: China
facility: The Affiliated Eye Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Provincial Hospital of Traditional Chinese Medicine
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
city: Ningbo
country: China
facility: Ningbo Eye Hospital
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
city: Quzhou
country: China
facility: People's Hospital of Quzhou
city: Shanghai
country: China
facility: Huashan Hospital
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
city: Shanghai
country: China
facility: Shanghai University of Traditional Chinese Medicine
city: Shanghai
country: China
facility: The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Shantou
country: China
facility: Shantou University-Chinese University of Hong Kong Joint Shantou International Eye Centre
city: Shenyang
country: China
facility: The Fourth People's Hospital of Shenyang
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Weifang
country: China
facility: Weifang Eye Hospital
city: Wenzhou
country: China
facility: Wenzhou Medical University Affiliated Optometry Hospital
city: Xingtai
country: China
facility: Hebei Provincial Eye Hospital
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Zhengzhou
country: China
facility: Henan Eye Center (Henan Eye Hospital)
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Zhengzhou
country: China
facility: The Second People's Hospital of Zhengzhou
city: Zunyi
country: China
facility: Zunyi Medical College
Study officials:
affiliation: Peking Union Medical College
name: Youxin Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Optometry Hospital of Wenzhou Medical University
name: Xiaolin Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University People's Hospital
name: Mingwei Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: Yi Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Hospital
name: Hong Dai, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chao Yang Hospital
name: Yong Tao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
name: Linna Lu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Oriental Hospital
name: Hongping Cui, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-sen Ophthalmic Center, Sun Yat-sen University
name: Xiaolin Liang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Pengxia Wan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yuqing Lan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shantou University-Chinese University of Hong Kong Joint Shantou International Eye Centre
name: Haoyu Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: Xiyuan Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Army Medical University (Southwest Hospital)
name: Xiaohong Meng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Eye Hospital of Nanchang University
name: Jinglin Yi, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: People's Hospital of Wuhan University (Hubei Provincial People's Hospital)
name: Hongmei Zheng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: People's Hospital of Quzhou
name: Liuhua Tong, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Eye Center (Henan Eye Hospital)
name: Zongming Song, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Shenzhi Liang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiangya Hospital of Central South University
name: Junfeng Mao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Jinan Second People's Hospital
name: Xiangwen Shu, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Yantai Yuhuangding Hospital
name: Yuanbin Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Zunyi Medical College
name: Shanjun Cai, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Hospital of Guizhou Medical University
name: Xian Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fourth People's Hospital of Shenyang
name: Xu Li, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Hospital of Nantong University
name: Rongrong Zhu, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu Provincial Hospital of Traditional Chinese Medicine
name: Wei Wei, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Yabin Sun, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Hospital of Anhui Medical University
name: Liming Tao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Aier Eye Hospital, Guangzhou
name: Hongjian Ma, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Hospital of Shanxi Medical University
name: Yaohong Wu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Fujian Medical University
name: Jian Guo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen People's Hospital
name: Xiaoling Luo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
name: Qiuhong Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai University of Traditional Chinese Medicine
name: Xinquan Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Provincial Eye Hospital
name: Lifei Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Hospital of Inner Mongolia Medical University
name: Dan Zhu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Eye Hospital of Shandong University of Chinese Medicine
name: Xuemei Pan, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Pingxiang People's Hospital
name: Yanfei Qiu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuzhou Central Hospital
name: Zhen Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Luoyang Third People's Hospital
name: Jingbo Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Weifang Eye Hospital
name: Xinyan Xu, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Kunming
name: Lan Li, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Jinzhong First People's Hospital
name: Hongxia Yang, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Provincial People's Hospital
name: Miaoqin Wu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Zhaozeng Lu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
name: Gangfeng Cui, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Ningbo Eye Hospital
name: Quanyong Yi, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second People's Hospital of Zhengzhou
name: Ruifeng Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
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