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

Neovascular (Wet) Age-related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05439629
• Other study ID #: BAT5906-004-CR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 28, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Bio-Thera Solutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 488
• Est. completion date: June 30, 2025
• Est. primary completion date: April 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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: ? intraretinal fluid; ? Lipid exudation in the retina; ? Subretinal fluid; (4) Subretinal hemorrhage; (5) Retinal pigment epithelium detachment; ? 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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular (Wet) Age-related Macular Degeneration

Intervention

Drug:
• BAT5906 injection
4.0 mg/eye/time, 50 µl, intravitreal injection
• Lucentis
0.5 mg/eye/time, 50 µl, intravitreal injection

Locations

Country	Name	City	State
China	Affiliated Hospital of Inner Mongolia Medical University	Beijing
China	Beijing Chao Yang Hospital	Beijing
China	Beijing Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing
China	Peking University People's Hospital	Beijing
China	Xiangya Hospital of Central South University	Changsha
China	The First Affiliated Hospital of Army Medical University (Southwest Hospital)	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	First Affiliated Hospital of Fujian Medical University	Fujian
China	First Affiliated Hospital, Sun Yat-Sen University	Guangzhou
China	Guangzhou Aier Eye Hospital	Guangzhou
China	Sun Yat-sen Ophthalmic Center, Sun Yat-sen University	Guangzhou
China	The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine	Guangzhou
China	Affiliated Hospital of Guizhou Medical University	Guiyang
China	Zhejiang Provincial People's Hospital	Hangzhou
China	The Second Hospital of Anhui Medical University	Hefei
China	People's Hospital of Wuhan University (Hubei Provincial People's Hospital)	Hubei
China	The First Hospital of Jilin University	Jilin
China	Jinan Second People's Hospital	Jinan
China	The Affiliated Eye Hospital of Shandong University of Chinese Medicine	Jinan
China	Jinzhong First People's Hospital	Jinzhong
China	The First People's Hospital of Kunming	Kunming
China	Luoyang Third People's Hospital	Luoyang
China	The Affiliated Eye Hospital of Nanchang University	Nanchang
China	Jiangsu Provincial Hospital of Traditional Chinese Medicine	Nanjing
China	Affiliated Hospital of Nantong University	Nantong
China	Ningbo Eye Hospital	Ningbo
China	Pingxiang People's Hospital	Pingxiang
China	People's Hospital of Quzhou	Quzhou
China	Huashan Hospital	Shanghai
China	Shanghai Oriental Hospital	Shanghai
China	Shanghai University of Traditional Chinese Medicine	Shanghai
China	The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Shantou University-Chinese University of Hong Kong Joint Shantou International Eye Centre	Shantou
China	The Fourth People's Hospital of Shenyang	Shenyang
China	Shenzhen People's Hospital	Shenzhen
China	Second Hospital of Shanxi Medical University	Taiyuan
China	Taizhou Hospital of Zhejiang Province	Taizhou
China	Weifang Eye Hospital	Weifang
China	Wenzhou Medical University Affiliated Optometry Hospital	Wenzhou
China	Hebei Provincial Eye Hospital	Xingtai
China	Xuzhou Central Hospital	Xuzhou
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Eye Center (Henan Eye Hospital)	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
China	The Second People's Hospital of Zhengzhou	Zhengzhou
China	Zunyi Medical College	Zunyi

Sponsors (1)

Lead Sponsor	Collaborator
Bio-Thera Solutions

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunogenicity evaluation	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.	Weeks 1 to 52
Primary	The change in the BCVA value	Compared to baseline, two groups of subjects studied the value of changes in ocular 52nd week BCVA	Week 52
Primary	The change in the BCVA value	Compared to baseline, two groups of subjects studied the changes in bcVA at weeks 12, 24, 36, and 48 of the eye	at weeks 12, 24, 36, and 48
Primary	BCVA increased the proportion of subjects with >10, >15, =30 words	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;	in the 24th and 52nd weeks
Primary	BCVA reduced the proportion of subjects < 10, < 15 words	Compared with baseline, the proportion of subjects in both groups who studied eye bcVA at weeks 24 and 52 decreased <10, < 15 words	at weeks 24 and 52
Primary	Changes in the thickness of the macular fovea (CRT).	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	at weeks 12, 24, 36, 48, and 52
Secondary	Vital signs	Number of participants with abnormal vital signs	Weeks 1 to 52
Secondary	physical examination	Number of participants with abnormal physical examination findings	Weeks 1 to 52
Secondary	Laboratory tests	Number of participants with abnormal laboratory test results	Weeks 1 to 52
Secondary	electrocardiogram( ECG )	Number of participants with abnormal ECG readings	Weeks 1 to 52
Secondary	Antibiotic antibodies (ADA)	Resistance antibody (ADA) situation in the subject	Weeks 1 to 52
Secondary	Adverse events(AE)	Ocular and non-ocular adverse events (AE) and serious adverse events (SAE)	Weeks 1 to 52
Secondary	Adverse events of particular concern (possible adverse reactions to the eye)	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	Weeks 1 to 52