A Phase 3 Study to Compare the Efficacy and Safety of HLX04-O with Ranibizumab in Subjects with WAMD

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)

This study will compare the efficacy and safety of HLX04-O administered by intravitreal injection (IVT) with ranibizumab in patients with active wAMD.

Study Overview

• Status: Completed
• Conditions: Age Related Macular Degeneration
• Intervention / Treatment: Drug: HLX04-O; Drug: ranibizumab

Detailed Description

This is 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). This study will be conducted in approximately 90 sites in different countries or regions.

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • The Alfred Hospital
  • Nedlands, Australia
    • Lions Eye Institute
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Lions Eye Institute
• Bulgaria
  • Burgas, Bulgaria
    • Specialized Eye Hospital For Active Treatment - Burgas Ltd
  • Montana, Bulgaria
    • Mhat Dr. Stamen Iliev Ad
  • Plovdiv, Bulgaria
    • Assoc. Prof. Dr. Desislava Koleva Aipsmaed Sveti Luka Eood
  • Plovdiv, Bulgaria
    • Medical Center Dar Plovdiv Ltd
  • Sofia, Bulgaria
    • DCC Aleksandrovska EOOD
  • Sofia, Bulgaria
    • Umhat Lozenets Ead
  • Sofia, Bulgaria
    • University First Mhat - Sofia Sv. Joan Krastitel Ead
  • Stara Zagora, Bulgaria
    • Medical Center Vereya Ltd
  • Varna, Bulgaria
    • Specialized Hospital For Active Treatment in Ophthalmology - Varna
  • Veliko Tarnovo
    • Gorna Oryahovitsa, Veliko Tarnovo, Bulgaria
      • Vizus Eood
• China
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou University Second Hospital
  • Guangdong
    • Shantou, Guangdong, China
      • Joint Shangtou International Eye Center Of Shantou University And The Chinese University Of Hong Kong
  • Henan
    • Xinxiang, Henan, China
      • The Third Affiliated Hospital of Xinxiang Medical University
  • Jilin
    • Changchun, Jilin, China
      • First Hospital of Jilin University
  • Ningxia
    • Yinchuan, Ningxia, China
      • The People's Hospital of Ningxia Hui Autonomous Region
  • Shandong
    • Weifang, Shandong, China
      • Weifang Eye Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai First Peoples's Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Eye Hospital
• Czechia
  • Pardubice, Czechia
    • Oftex Ocni Klinika
• France
  • Amiens, France
    • Centre Hospitalier Universitaire Amiens-Picardie Service D'Ophthalmologie Amiens France
  • Paris, France
    • University Eye Clinic Centre Hospitalier Creteil Paris France
• Germany
  • Bonn, Germany
    • Ukb University of Bonn
  • Freiburg, Germany
    • University Hospital Freiburg
  • Giessen, Germany
    • Justus Liebig University Giessen
  • Mainz, Germany
    • Johannes Gutenberg University Mainz
  • Munster, Germany
    • St Franziskus Hospital Munster
  • Sulzbach, Germany
    • Eye Clinic Sulzbach
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem
  • Budapest, Hungary
    • Bajcsy-Zsilinszky Korhaz es Rendelointezet
  • Eger, Hungary
    • Markhot Ferenc Oktatokorhaz és Rendelointezet
  • Pecs, Hungary
    • Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika
  • Pécs, Hungary
    • Ganglion Orvosi Központ
  • Szeged, Hungary
    • Szegedi Tudomanyegyetem Aok Szakk
• Italy
  • Milan, Italy
    • Clinica Oculistica Ospedale Luigi Sacco, Universita' Degli Studi Di Milano
  • Milan, Italy
    • Clinica Oculistica Universita Vita Salute - Irccs Ospedale San Raffaele
  • Rome, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli - Irccs Uoc Oculistica
  • Rome, Italy
    • Irccs Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia Onlus Rome, Italy
• Latvia
  • Riga, Latvia
    • Riga East University Hospital
  • Riga, Latvia
    • P Stradina Clinical University Hospital
• Poland
  • Bydgoszcz, Poland
    • Oftalmika Sp Z.O.O
  • Katowice, Poland
    • Centrum Klinicke Oftalmologie S.R.O
  • Kraków, Poland
    • Szpital Sw. Rozy
  • Lublin, Poland
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline
  • Poznan, Poland
    • Szpital SW Wojciecha
  • Tarnowskie Góry, Poland
    • Caminomed Wojciech Jedrzejewski
  • Tarnów, Poland
    • Centrum Medyczne UNO-MED
  • Walbrzych, Poland
    • Centrum Medyczne Piasta 47
  • Warsaw, Poland
    • Nzoz Optimed
  • Warszawa, Poland
    • Retina Okulistyka Sp.Z O.O.Sp.K.
  • Podlaskie
    • Bialystok, Podlaskie, Poland
      • NZOZ E-Vita
  • WA
    • Krakow, WA, Poland
      • Centrum Medyczne Promed
• Serbia
  • Belgrade, Serbia
    • Special Optalmological Hospital Belgrade
  • Belgrade, Serbia
    • Zvezdara University Medical Center
• Singapore
  • Singapore, Singapore
    • National University Hospital
• Slovakia
  • Banská Bystrica, Slovakia
    • Ocna Klinika Szu F.D.R.Banska Bystrica
  • Nitra, Slovakia
    • Fakultna nemocnica Nitra
  • Nové Zámky, Slovakia
    • Fakultna Nemocnica S Poliklinikou Nove Zamky Oftalmologicke Nelozkove Oddelenie
  • Poprad, Slovakia
    • Nemocnica Poprad As Oftalmologicke Oddelenie Jzs
  • Trebišov, Slovakia
    • Nemocnica S Poliklinikou Trebisov A.S. Ocne Oddelenie Jzs
  • Trenčianske Teplice, Slovakia
    • Fakultna nemocnica Trencin
  • Žilina, Slovakia
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Alicante, Spain
    • VISSUM
  • Barcelona, Spain
    • Hospital Universitari Vall d Hebron
  • Barcelona, Spain
    • Centro de Oftalmologia Barraquer
  • Barcelona, Spain
    • Institito de Microcirugia Ocular
  • Barcelona, Spain
    • Institut Catala de la Retina
  • Burjassot, Spain
    • Oftalvist Clinic
  • Cordoba, Spain
    • Hospital La Arruzafa
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro
  • Oviedo, Spain
    • Instituto Oftalmologico Fernandez-Vega
  • Pamplona, Spain
    • Clinica Universitario de Navarra
  • San Sebastián, Spain
    • Hospital Universitario Donostia
  • Sant Cugat Del Valles, Spain
    • Omiq Hospital General de Catalunya
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain
    • Consorcio Hospital General Universitario de Valencia
  • Valencia, Spain
    • Clinica Oftalmologica Aiken
  • Valencia, Spain
    • Fisabio Oftalmologia Medica
  • Valladolid, Spain
    • Hospital Rio Hortega
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Associated Retina Consultants-Gilbert
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants-Phoenix
  • California
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Glendale, California, United States, 91204
      • Global Research Management
    • Huntington Beach, California, United States, 92647
      • VMR Institute
    • Huntington Beach, California, United States, 92647
      • Atlantis Eyecare, VMR Institute
    • Long Beach, California, United States, 90807
      • South Coast Retina Center
    • Los Alamitos, California, United States, 90720
      • Retina Consultants of Orange County
    • Los Angeles, California, United States, 90048
      • MACRO Trials/ Lazar Retina
    • Torrance, California, United States, 90505
      • East West Eye Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Retina Consultants of Southern Colorado
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Florida Retina Institute-Orlando
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute-Orlando
    • Tampa, Florida, United States, 33612
      • University of South Florida
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Chicago, Illinois, United States, 60637
      • The University of Chicago, IL
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Butchertown Clinical Trials
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Retina Consultants of Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Mississippi Retina Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates
    • Asheville, North Carolina, United States, 27103
      • Piedmont Retina Specialists
    • Hickory, North Carolina, United States, 28602
      • Graystone Eye
    • Wake Forest, North Carolina, United States, 27332
      • North Carolina Retina Associates
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research, LLC
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Retina Consultants of Charleston - Beaufort
    • Charleston, South Carolina, United States, 29414
      • Retina Consultants of Charleston: Charleston Neuroscience Institute
    • Florence, South Carolina, United States, 29501
      • Carolina Center for Sight
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Retina Consultants of Nashville
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of TEXAS- Newcastle
    • Houston, Texas, United States, 77015
      • Mt. Olympus Research-Garcia
    • Houston, Texas, United States, 77015
      • Mt. Olympus Research/Museum Eye District
    • Round Rock, Texas, United States, 78681
      • Retina Consultants of TEXAS - Round Rock
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina Consultants
    • Salt Lake City, Utah, United States, 84107
      • Retina Associates of Utah, PLLC
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Emerson Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Capable to understand and sign the informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Women or men aged ≥50 years when signing the ICF.
3. In the Investigator's judgment, willing and able to complete all visits and assessments adhering to the prohibitions and restrictions specified in this protocol.
4. Newly diagnosed, untreated, active CNV lesions secondary to age-related macular degeneration that affect the central subfield (CSF) in the study eye. Active CNV was defined as leakage on fluorescein angiography (FA) and subretinal or intraretinal fluid on optical coherence tomography (OCT) with confirmation of the reading center during screening.
5. 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
6. The BCVA letters between 24 and 73, inclusive, in the study eye, using Early Treatment Diabetic Retinopathy Study (ETDRS) charts.
7. Participants' fellow (non-study) eye must have a BCVA of 24 letters or better.
8. Clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm the diagnosis.

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,pathological myopia, etc.) with confirmation of the reading center.
2. The fellow (non-study) 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. Aphakia (except intraocular lens) or posterior capsular rupture of the lens (except yttrium-aluminium-garnet (YAG) laser posterior capsulotomy after intraocular lens implantation ≥30 days prior to first dose) in the study eye.
4. 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.
5. Vitreous hemorrhage in the study eye within 3 months prior to dose 1.
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 in the study eye (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.)
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 (except the surgery mentioned in exclusion 10 ,such as cataract surgery, etc.) within 3 months prior to dose 1, or current unhealed wound, moderate or severe ulcer or fracture in the study eye.
12. Subconjunctival or intraocular use of corticosteroids within 3 months (including subconjunctival or intraocular long-acting implant within 6 months) prior to dose 1 in the study eye. Use of systemic corticosteroids for 30 or more consecutive days within 3 months prior to dose 1. Inhaled, nasal or dermal steroids are permitted. Topical ocular corticosteroids administered for 30 or more consecutive days in the study eye within 3 months prior to dose 1.
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 3 months or the duration of 5 half-lives of the study drug (which is longer) before the first dose and have used the test drug or received device treatment.
15. Pregnancy or lactation, or fertile men or women not willing to use effective contraception from the day when ICF was signed to at least 6 months following the last dose of study intervention.

16. Infertile women or men 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.

    Fertile women or men fail to meet either 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 study intervention. Effective contraceptive methods with a failure rate of <1% per year, including 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 to dose 1, 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(PT) or International normalized ratio (INR) ≥ 1.5 ×ULN, or activated partial thromboplastin time (aPTT) ≥1.5 ×ULN, and is clinically significant in the opinion of the Investigator.
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 (e.g., stroke, myocardial infarction).
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 human immunodeficiency virus (HIV) infection or positive for 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 within 2weeks prior to the first dose, or still symptomatic from an earlier infection (except symptoms associated with "Long COVID "), or displaying symptoms consistent with COVID-19 in the absence of a confirmed Covid-19 infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX04-O; Biologic recombinant anti-VEGF humanized monoclonal antibody	Drug: HLX04-O; Biologic recombinant anti-VEGF humanized monoclonal antibody, developed by Shanghai Henlius Biotech, Inc.
Active Comparator: Ranibizumab; Biologic anti-VEGF recombinant humanized monoclonal antibody fragment	Drug: ranibizumab; Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in BCVA at at Week 36	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to at Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients gaining at least 15 letters in the BCVA at Week 12, 24, 36 and 48	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 12, 24, 36 and 48
Proportion of patients gaining at least 10 letters in the BCVA at Week 12, 24, 36 and 48	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 12, 24, 36 and 48
Proportion of patients gaining at least 5 letters in the BCVA at Week 12, 24, 36 and 48	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 12, 24, 36 and 48
• Mean change from baseline in size of CNV and total area of fluorescein leakage from CNV on FA at Week 12, 36 and 48 (as measured by the Reading Center)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 12, 36 and 48
• Mean change from baseline in CRT on OCT at Week 12, 24, 36 and 48 (as measured by the Reading Center)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to week 12, 24, 36 and 48
Change from baseline in NEI VFQ-25 scale score at Week 12, 36, and 48.	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 12, 36, and 48
Key Secondary Outcome : Mean change from baseline in BCVA at Week 48.	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 48
Mean change in BCVA over time	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 48

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: HLX04-O-wAMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No