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

NCT ID: NCT04740671

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2024-12-31

Brief Summary

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

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.

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

Intervention Type: DRUG

Biologic recombinant anti-VEGF humanized monoclonal antibody, developed by Shanghai Henlius Biotech, Inc.

Ranibizumab

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Group Type: ACTIVE_COMPARATOR

ranibizumab

Intervention Type: DRUG

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Interventions

HLX04-O

Biologic recombinant anti-VEGF humanized monoclonal antibody, developed by Shanghai Henlius Biotech, Inc.

Intervention Type: DRUG

ranibizumab

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Intervention Type: DRUG

Eligibility Criteria

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.

• 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

Associated Retina Consultants-Gilbert

Gilbert, Arizona, United States

Associated Retina Consultants-Phoenix

Phoenix, Arizona, United States

Retina Consultants of Orange County

Fullerton, California, United States

Global Research Management

Glendale, California, United States

Atlantis Eyecare, VMR Institute

Huntington Beach, California, United States

VMR Institute

Huntington Beach, California, United States

South Coast Retina Center

Long Beach, California, United States

Retina Consultants of Orange County

Los Alamitos, California, United States

MACRO Trials/ Lazar Retina

Los Angeles, California, United States

East West Eye Institute

Torrance, California, United States

Retina Consultants of Southern Colorado

Colorado Springs, Colorado, United States

Florida Retina Institute-Orlando

Jacksonville, Florida, United States

Florida Retina Institute-Orlando

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Center for Retina and Macular Disease

Winter Haven, Florida, United States

Southeast Retina Center

Augusta, Georgia, United States

The University of Chicago, IL

Chicago, Illinois, United States

The University of Chicago

Chicago, Illinois, United States

Illinois Retina Associates

Oak Park, Illinois, United States

Retina Associates LLC

Lenexa, Kansas, United States

Butchertown Clinical Trials

Louisville, Kentucky, United States

Cumberland Valley Retina Consultants

Hagerstown, Maryland, United States

Retina Consultants of Minnesota

Edina, Minnesota, United States

VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota

Saint Louis Park, Minnesota, United States

Mississippi Retina Associates

Jackson, Mississippi, United States

Piedmont Retina Specialists

Asheville, North Carolina, United States

Western Carolina Retinal Associates

Asheville, North Carolina, United States

Graystone Eye

Hickory, North Carolina, United States

North Carolina Retina Associates

Wake Forest, North Carolina, United States

Verum Research, LLC

Eugene, Oregon, United States

Retina Consultants of Charleston - Beaufort

Beaufort, South Carolina, United States

Retina Consultants of Charleston: Charleston Neuroscience Institute

Charleston, South Carolina, United States

Carolina Center for Sight

Florence, South Carolina, United States

Retina Consultants of Nashville

Nashville, Tennessee, United States

Retina Consultants of TEXAS- Newcastle

Bellaire, Texas, United States

Mt. Olympus Research-Garcia

Houston, Texas, United States

Mt. Olympus Research/Museum Eye District

Houston, Texas, United States

Retina Consultants of TEXAS - Round Rock

Round Rock, Texas, United States

Retina Consultants of Texas

The Woodlands, Texas, United States

Retina Associates of Utah, PLLC

Salt Lake City, Utah, United States

Rocky Mountain Retina Consultants

Salt Lake City, Utah, United States

Emerson Clinical Research Institute

Falls Church, Virginia, United States

Lions Eye Institute

Nedlands, Western Australia, Australia

The Alfred Hospital

Melbourne, , Australia

Lions Eye Institute

Nedlands, , Australia

Mhat Dr. Stamen Iliev Ad

Montana, Montana, Bulgaria

Assoc. Prof. Dr. Desislava Koleva Aipsmaed Sveti Luka Eood

Plovdiv, Plovdiv, Bulgaria

Dcc Aleksandrovska Eood

Sofia, Sofia, Bulgaria

Umhat Lozenets Ead

Sofia, Sofia, Bulgaria

University First Mhat - Sofia Sv. Joan Krastitel Ead

Sofia, Sofia, Bulgaria

Specialized Hospital For Active Treatment in Ophthalmology - Varna

Varna, Varna, Bulgaria

Vizus Eood

Gorna Oryahovitsa, Veliko Tarnovo, Bulgaria

Specialized Eye Hospital For Active Treatment - Burgas Ltd

Burgas, , Bulgaria

Medical Center Dar Plovdiv Ltd

Plovdiv, , Bulgaria

Medical Center Vereya Ltd

Stara Zagora, , Bulgaria

Lanzhou University Second Hospital

Lanzhou, Gansu, China

Joint Shangtou International Eye Center Of Shantou University And The Chinese University Of Hong Kong

Shantou, Guangdong, China

The Third Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, China

First Hospital of Jilin University

Changchun, Jilin, China

The People's Hospital of Ningxia Hui Autonomous Region

Yinchuan, Ningxia, China

Weifang Eye Hospital

Weifang, Shandong, China

Shanghai First Peoples's Hospital

Shanghai, Shanghai Municipality, China

Shanxi Eye Hospital

Taiyuan, Shanxi, China

Oftex Ocni Klinika

Pardubice, , Czechia

Centre Hospitalier Universitaire Amiens-Picardie Service D'Ophthalmologie Amiens France

Amiens, , France

University Eye Clinic Centre Hospitalier Creteil Paris France

Paris, , France

Ukb University of Bonn

Bonn, , Germany

University Hospital Freiburg

Freiburg im Breisgau, , Germany

Justus Liebig University Giessen

Giessen, , Germany

Johannes Gutenberg University Mainz

Mainz, , Germany

St Franziskus Hospital Munster

Münster, , Germany

Eye Clinic Sulzbach

Sulzbach, , Germany

Bajcsy-Zsilinszky Korhaz Es Rendelointezet

Budapest, Budapest, Hungary

Semmelweis Egyetem

Budapest, , Hungary

Markhot Ferenc Oktatokorhaz Es Rendelointezet

Eger, , Hungary

Ganglion Orvosi Kozpont

Pécs, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika

Pécs, , Hungary

Szegedi Tudomanyegyetem Aok Szakk

Szeged, , Hungary

Irccs Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia Onlus Rome, Italy

Rome, Rome, Italy

Clinica Oculistica Ospedale Luigi Sacco, Universita' Degli Studi Di Milano

Milan, , Italy

Clinica Oculistica Universita Vita Salute - Irccs Ospedale San Raffaele

Milan, , Italy

Fondazione Policlinico Universitario Agostino Gemelli - Irccs Uoc Oculistica

Rome, , Italy

P Stradina Clinical University Hospital

Riga, , Latvia

Riga East University Hospital

Riga, , Latvia

Nzoz E-Vita

Bialystok, Podlaskie Voivodeship, Poland

Centrum Medyczne Promed

Krakow, WA, Poland

Oftalmika Sp Z.O.O

Bydgoszcz, , Poland

Centrum Klinicke Oftalmologie S.R.O

Katowice, , Poland

Szpital SW. Rozy

Krakow, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline

Lublin, , Poland

Szpital SW Wojciecha

Poznan, , Poland

Caminomed Wojciech Jedrzejewski

Tarnowskie Góry, , Poland

Centrum Medyczne Uno-Med

Tarnów, , Poland

Nzoz Optimed

Warsaw, , Poland

Retina Okulistyka Sp.Z O.O.Sp.K.

Warsaw, , Poland

Centrum Medyczne Piasta 47

Wałbrzych, , Poland

Special Optalmological Hospital Belgrade

Belgrade, , Serbia

Zvezdara University Medical Center

Belgrade, , Serbia

National University Hospital

Singapore, , Singapore

Ocna Klinika Szu F.D.R.Banska Bystrica

Banská Bystrica, , Slovakia

Fakultna Nemocnica Nitra

Nitra, , Slovakia

Fakultna Nemocnica S Poliklinikou Nove Zamky Oftalmologicke Nelozkove Oddelenie

Nové Zámky, , Slovakia

Nemocnica Poprad As Oftalmologicke Oddelenie Jzs

Poprad, , Slovakia

Nemocnica S Poliklinikou Trebisov A.S. Ocne Oddelenie Jzs

Trebišov, , Slovakia

Fakultna Nemocnica Trencin

Trenčianske Teplice, , Slovakia

Fakultna Nemocnica S Poliklinikou Zilina

Žilina, , Slovakia

VISSUM

Alicante, , Spain

Centro de Oftalmologia Barraquer

Barcelona, , Spain

Hospital Universitari Vall D Hebron

Barcelona, , Spain

Institito de Microcirugia Ocular

Barcelona, , Spain

Institut Catala de La Retina

Barcelona, , Spain

Oftalvist Clinic

Burjassot, , Spain

Hospital La Arruzafa

Córdoba, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Instituto Oftalmologico Fernandez-Vega

Oviedo, , Spain

Clinica Universitario de Navarra

Pamplona, , Spain

Hospital Universitario Donostia

San Sebastián, , Spain

Omiq Hospital General de Catalunya

Sant Cugat del Vallès, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Clinica Oftalmologica Aiken

Valencia, , Spain

Consorcio Hospital General Universitario de Valencia

Valencia, , Spain

Fisabio Oftalmologia Medica

Valencia, , Spain

Hospital Rio Hortega

Valladolid, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

United States; Australia; Bulgaria; China; Czechia; France; Germany; Hungary; Italy; Latvia; Poland; Serbia; Singapore; Slovakia; Spain

Other Identifiers

HLX04-O-wAMD

Identifier Type: -

Identifier Source: org_study_id