Compare the Efficacy and Safety of HLX04-O with Ranibizumab in Subjects with WAMD

NCT ID: NCT05003245

Last Updated: 2025-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 407 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2024-05-07

Brief Summary

this study will compare the efficacy and safety of HLX04-O administered by IVT with ranibizumab in patients with active CNV secondary to AMD.

Detailed Description

This is a Phase 3, multicenter, randomized double masked active controlled study to compare the efficacy and safety of HLX04-O administered by IVT with ranibizumab in patients with active CNV secondary to AMD. The study will be conducted in approximately 60 sites in China.

Either HLX04-O (1.25 mg) IVT or ranibizumab (0.5 mg) IVT will be administered at a 4-week interval for 1 year (12 cycles).

Conditions

Age Related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

HLX04-O

Biologic recombinant anti-VEGF humanized monoclonal antibody

Group Type: EXPERIMENTAL

HLX04-O，recombinant anti-vascular endothelial growth factor (VEGF) humanized monoclonal antibody ophthalmic injection

Intervention Type: DRUG

0.05mL solution at a 4-week interval for intravitreal injection

Ranibizumab

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Group Type: ACTIVE_COMPARATOR

Lucentis

Intervention Type: DRUG

0.05mL solution at a 4-week interval for intravitreal injection

Interventions

HLX04-O，recombinant anti-vascular endothelial growth factor (VEGF) humanized monoclonal antibody ophthalmic injection

0.05mL solution at a 4-week interval for intravitreal injection

Intervention Type: DRUG

Lucentis

0.05mL solution at a 4-week interval for intravitreal injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Capable to understand and sign the informed consent form (ICF) which includes compliance with the ICF and this protocol. In the Investigator's judgment, willing and able to complete all visits and assessments adhering to the prohibitions and restrictions specified in this protocol.

2. Women or men aged ≥50 years when signing the ICF.

3. Newly diagnosed, untreated, active subfoveal or juxtafoveal CNV lesions secondary to AMD in the study eye. (Active CNV was defined as leakage on FA and subretinal or intraretinal fluid on OCT with confirmation of the reading center during screening).

4. The total lesion area (including hemorrhage, scar and neovascularization) of the study eye ≤12 disc area (DA) with confirmation of the reading center before randomization a.

5. The BCVA letters between 24 and 73, inclusive, in the study eye, using Early Treatment Diabetic Retinopathy Study (ETDRS) charts.

6. Clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm the diagnosis.

7. Participants' fellow (non-study) eye must have had a BCVA of 24 letters or better.

Exclusion Criteria

1. Macular-related retinal pigment epithelial tears in the study eye; scar, fibrosis or atrophy involving the fovea, or CNV due to other causes in the study eye (e.g., ocular histoplasmosis, trauma, or pathological myopia etc.) with confirmation of the reading center.

2. The fellow (nonstudy) eye needs anti-VEGF IVT injection (e.g. CNV due to wAMD, trauma, pathological myopia, retina vein occlusion, diabetic macular edema, etc) in the next 3 months after randomization, in the investigator's judgment.

3. Active or recent (within 1 month prior to dose 1) intraocular, extraocular or periocular infection (including conjunctivitis, keratitis, scleritis or endophthalmitis), or history of idiopathic or autoimmune-associated uveitis in either eye.

4. Vitreous hemorrhage in the study eye within 3 months prior to dose 1.

5. Aphakia (except intraocular lens) or posterior capsular rupture of the lens (except yttrium aluminium-garnet (YAG) laser posterior capsulotomy after intraocular lens implantation ≥1 month prior to first dose) in the study eye.

6. Corneal dystrophy or history of corneal transplantation, scleral softening or history of scleral softening, history of rhegmatogenous retinal detachment or macular hole (Stage II, III or IV) in the study eye.

7. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥25 mmHg despite treatment with antiglaucoma medication), and/or glaucoma filtering surgery (e.g., trabeculectomy, scleral nipping, non-penetrating trabeculectomy, etc.), or advanced glaucoma resulting in a cup/disc ratio >0.8 in the study eye

8. Equivalent spherical diopter of the study eye ≥-8D. For participants who had undergone refractive correction or cataract surgery, the equivalent spherical diopter of the study eye before surgery ≥-8D.

9. Estimated by the Investigator, any concurrent intraocular condition except wAMD (e.g., diabetic retinopathy, dry AMD, retina vein occlusion, uveitis, angioid streaks, retinal detachment, epiretinal membrane, amblyopia, central serous chorioretinopathy, etc.) in the study eye that limited the potential to gain visual acuity upon treatment with the investigational product, or could have required medical or surgical intervention during the study to prevent or treat visual loss.

10. Underwent intraocular surgery including verteporfin photodynamic therapy (PDT), transpupillary thermotherapy, macular translocation, vitrectomy, laser photocoagulation in macular area, other surgery in macular area or surgery to treat AMD.

11. Previous extraocular or periocular surgery within 1 month or intraocular surgery (including cataract surgery, etc.) within 3 months prior to dose 1, or current unhealed wound, moderate or severe ulcer or history of fracture in the study eye.

12. Subconjunctival or intraocular or systemic use of corticosteroids within 3 months (including subconjunctival or intraocular long-acting implant within 6 months) prior to dose 1 in the study eye.

13. Previous systemic anti-VEGF therapy or IVT injection of any anti-VEGF drug into either eye or other ocular use of anti-VEGF drug within 3 months prior to dose 1.

14. Participated in any drug (other than vitamins and minerals) or device clinical trials within 3 months or the duration of 5 half-lives of the study drug (which is longer) prior to dose 1 and have used the test drug or received device treatment.

15. Pregnancy or lactation.

16. Infertile women fail to meet either of the following ones: 1) menopause (≥12 continuous months of amenorrhea with no identified cause other than menopause before screening); 2) surgically sterilized.

Men or fertile women fail to meet both of the following ones: 1) women of childbearing potential must have a negative urine or serum pregnancy test result within 14 days prior to initiation of the study intervention, and should not breastfeed; If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test; 2) agreement to remain abstinent (refrain from heterosexual intercourse) or use effective contraceptive methods from signed ICF to at least 6 months following the last dose of the study intervention. Effective contraceptive methods include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs.

17. In the Investigator's judgment, there is evidence of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the participant at high risk for treatment complications (e.g. stroke or myocardial infarction within 6 months prior todose1, uncontrolled hypertension (systolic blood pressure≥160 mmHg, or diastolic blood pressure ≥100 mmHg), etc.).

18. Uncontrolled diabetes (defined as HbA1c>10.0%).

19. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) is more than twice the upper limit of normal (ULN), and/or serum creatinine is 1.2 times more than the ULN, and is clinically significant in the opinion of the Investigator.

20. Abnormal coagulation function（prothrombin time ≥ 3 seconds over ULN, activated partial thromboplastin time ≥ 10 seconds over ULN）

21. Active disseminated intravascular coagulation and obvious bleeding tendency within 3 months prior to dose 1.

22. Evidence of significant uncontrolled concomitant diseases such as cardiovascular diseases, nervous system diseases, respiratory system diseases, urinary system diseases, digestive system diseases and endocrine diseases.

23. Current treatment for active systemic infection, or history of recurrent serious infections.

24. Known active or suspected autoimmune diseases, requiring systemic immunosuppressive therapy.

25. Positive for syphilis screening test or positive for human immunodeficiency virus (HIV) screening test.

26. Known allergy to any component of the study intervention or history of allergy to fluorescein or indocyanine green, any anesthetics or antimicrobial agents used during the course of the study.

27. In the Investigator's judgment, other conditions considered not amenable to this study.

28. Participant who has been diagnosed to be COVID-19 or who has received COVID-19 vaccine within 1 month prior to dose 1.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Henlius Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The first affiliated hospital of bengbu medical college

Bengbu, Anhui, China

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Beijing Tongren Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Third Military Medical University (Southwest Hospital)

Chongqing, Chongqing Municipality, China

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

The Second Hospital of Lanzhou University

Lanzhou, Gansu, China

The First Affiliated Hospital of Jinan University (Guangzhou Overseas Chinese Hospital )

Guangzhou, Guangdong, China

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Jieyang People's Hospital

Jieyang, Guangdong, China

The First Affiliated Hospital of Guangxi Medical University

Nanjing, Guangxi, China

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, China

Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

The First People's Hospital of Zunyi

Zunyi, Guizhou, China

Cangzhou Central Hospital

Cangzhou, Hebei, China

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Luoyang Third People's Hospital

Luoyang, Henan, China

The First Affiliated Hospital of Xinxiang Medical College

Xinxiang, Henan, China

The Third Affiliated Hospital of Xinxiang Medical College

Xinxiang, Henan, China

Henan Eye Hospital

Zhengzhou, Henan, China

People's Hospital of Wuhan University (Hubei Provincial People's Hospital)

Wuhan, Hubei, China

Tongji hospital, Tongji medical college, Huazhong University of Science and Technology

Wuhan, Hubei, China

Wuhan AIER Eye Hospital

Wuhan, Hubei, China

Wuhan Puren Hospital

Wuhan, Hubei, China

Yichang Central People's Hospital

Yichang, Hubei, China

Affiliated Eye Hospital of Nanchang University

Nanchang, Jiangxi, China

the First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Pingxiang People's Hospital

Pingxiang, Jiangxi, China

The First Hospital of Jilin University

Jilin, Jilin, China

Shenyang AIER Eye Hospital

Shenyang, Liaoning, China

Ningxia Hui Autonomous Region Peoples Hospital

Yinchuan, Ningxia, China

Shangdong Provincial Hospital

Jinan, Shandong, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Weifang Eye Hospital

Weifang, Shandong, China

Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, China

Shanxi Eye Hospital

Taiyuan, Shanxi, China

Tianjin Eye Hospital

Tianjin, Tianjin Municipality, China

Zhejiang provincial people's hospital

Hangzhou, Zhejiang, China

Lishui Municioal Central Hospital

Lishui, Zhejiang, China

Countries

China

Other Identifiers

HLX04-O-wAMD-CN

Identifier Type: -

Identifier Source: org_study_id