Clinical trial NCT05003245: Compare the Efficacy and Safety of HLX04-O with Ranibizumab in Subjects with WAMD
Official title: A Phase 3 Randomized Double-masked Active Controlled Study to Compare the Efficacy and Safety of HLX04-O Administered by Intravitreal Injection with Ranibizumab in Subjects with Wet Age Related Macular Degeneration (wAMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Age Related Macular Degeneration
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2021-08-12
Enrollment: 407
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Other protocol defined inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Mean change of letters from baseline in best-corrected visual acuity (BCVA) at Week 48.
timeFrame: from baseline to week 48
Secondary outcomes:
measure: Mean change of letters from baseline in the BCVA over time
timeFrame: From baseline to week 48
measure: Proportion of patients gaining at least 15/10/5 letters in the BCVA at Week 12, 24, 36 and 48
timeFrame: From baseline to week 48
measure: Mean change from baseline in the total area of CNV and the total area of fluorescein leakage on fluorescein angiography (FA) at Week 12, 24 and 48
timeFrame: From baseline to week 48
measure: Mean change from baseline in central retina thickness (CRT) on optical coherence tomography (OCT) at Week 12, 24, 36 and 48
timeFrame: From baseline to week 48
measure: Change from baseline in National Eye Institute Visual Functioning Questionnaire - 25 scale score at Week 12, 24, and 48
timeFrame: From baseline to week 48
measure: Percentage and severity of ocular AEs (IVT procedure related and Investigation Medication related), non-ocular AEs; laboratory abnormalities; vital sign, physical examination abnormalities, etc.
timeFrame: From baseline to week 48
measure: Incidence of ADAs and NAbs against HLX04-O following IVT administration
timeFrame: From baseline to week 48
measure: HLX04-O serum concentrations before Dose 1, Dose 2, Dose 6, Dose 9 and Dose 12 and the last visit as data permit.
timeFrame: From baseline to week 48
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Third Military Medical University (Southwest Hospital)
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Lanzhou
country: China
facility: The Second Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University (Guangzhou Overseas Chinese Hospital )
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Nanjing
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zunyi
country: China
facility: The First People's Hospital of Zunyi
state: Guizhou
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Ha'erbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Third People's Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Xinxiang
country: China
facility: The Third Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Zhengzhou
country: China
facility: Henan Eye Hospital
state: Henan
city: Wuhan
country: China
facility: People's Hospital of Wuhan University (Hubei Provincial People's Hospital)
state: Hubei
city: Wuhan
country: China
facility: Tongji hospital, Tongji medical college, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan AIER Eye Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Puren Hospital
state: Hubei
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Nanchang
country: China
facility: Affiliated Eye Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: the First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Jilin
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shenyang AIER Eye Hospital
state: Liaoning
city: Yinchuan
country: China
facility: Ningxia Hui Autonomous Region Peoples Hospital
state: Ningxia
city: Jinan
country: China
facility: Shangdong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weifang
country: China
facility: Weifang Eye Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Eye Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Eye Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang provincial people's hospital
state: Zhejiang
city: Lishui
country: China
facility: Lishui Municioal Central Hospital
state: Zhejiang
Study officials:
References: