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

Phase 3

Completed

• Conditions: Age Related Macular Degeneration
• Interventions: Drug: HLX04-O; Drug: ranibizumab

• Registration Number: NCT04740671
• Lead Sponsor: Shanghai Henlius Biotech

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.

Study Timeline

• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-02-02
• Study First Posted: 2021-02-05
• Study Start: 2021-07-01
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-01
• Last Update Posted: 2025-01-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 410

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HLX04-O	HLX04-O	Biologic recombinant anti-VEGF humanized monoclonal antibody
Ranibizumab	ranibizumab	Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (123)

Fakultna Nemocnica S Poliklinikou Nove Zamky Oftalmologicke Nelozkove Oddelenie; 🇸🇰 Nové Zámky, Slovakia

Instituto Oftalmologico Fernandez-Vega; 🇪🇸 Oviedo, Spain

Associated Retina Consultants-Gilbert; 🇺🇸 Gilbert, Arizona, United States

VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota; 🇺🇸 Saint Louis Park, Minnesota, United States

MACRO Trials/ Lazar Retina; 🇺🇸 Los Angeles, California, United States

East West Eye Institute; 🇺🇸 Torrance, California, United States

Cumberland Valley Retina Consultants; 🇺🇸 Hagerstown, Maryland, United States

Piedmont Retina Specialists; 🇺🇸 Asheville, North Carolina, United States

Mississippi Retina Associates; 🇺🇸 Jackson, Mississippi, United States

Western Carolina Retinal Associates; 🇺🇸 Asheville, North Carolina, United States

Retina Consultants of Texas; 🇺🇸 The Woodlands, Texas, United States

Global Research Management; 🇺🇸 Glendale, California, United States

Retina Consultants of Minnesota; 🇺🇸 Edina, Minnesota, United States

Specialized Eye Hospital For Active Treatment - Burgas Ltd; 🇧🇬 Burgas, Bulgaria

Assoc. Prof. Dr. Desislava Koleva Aipsmaed Sveti Luka Eood; 🇧🇬 Plovdiv, Bulgaria

Dcc Aleksandrovska Eood; 🇧🇬 Sofia, Bulgaria

St Franziskus Hospital Munster; 🇩🇪 Munster, Germany

Markhot Ferenc Oktatokorhaz Es Rendelointezet; 🇭🇺 Eger, Hungary

Ganglion Orvosi Kozpont; 🇭🇺 Pécs, Hungary

Clinica Oculistica Ospedale Luigi Sacco, Universita' Degli Studi Di Milano; 🇮🇹 Milan, Italy

Clinica Oculistica Universita Vita Salute - Irccs Ospedale San Raffaele; 🇮🇹 Milan, Italy

Centrum Medyczne Promed; 🇵🇱 Krakow, WA, Poland

Fondazione Policlinico Universitario Agostino Gemelli - Irccs Uoc Oculistica; 🇮🇹 Rome, Italy

Special Optalmological Hospital Belgrade; 🇷🇸 Belgrade, Serbia

Oftalvist Clinic; 🇪🇸 Burjassot, Spain

Mt. Olympus Research/Museum Eye District; 🇺🇸 Houston, Texas, United States

Szpital SW. Rozy; 🇵🇱 Kraków, Poland

Shanghai First Peoples's Hospital; 🇨🇳 Shanghai, Shanghai, China

Retina Associates LLC; 🇺🇸 Lenexa, Kansas, United States

Retina Consultants of Nashville; 🇺🇸 Nashville, Tennessee, United States

Retina Associates of Utah, PLLC; 🇺🇸 Salt Lake City, Utah, United States

Rocky Mountain Retina Consultants; 🇺🇸 Salt Lake City, Utah, United States

Associated Retina Consultants-Phoenix; 🇺🇸 Phoenix, Arizona, United States

Retina Consultants of Orange County; 🇺🇸 Los Alamitos, California, United States

Atlantis Eyecare, VMR Institute; 🇺🇸 Huntington Beach, California, United States

VMR Institute; 🇺🇸 Huntington Beach, California, 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

University of South Florida; 🇺🇸 Tampa, Florida, United States

Graystone Eye; 🇺🇸 Hickory, North Carolina, United States

Retina Consultants of Charleston - Beaufort; 🇺🇸 Beaufort, South Carolina, United States

Verum Research, LLC; 🇺🇸 Eugene, Oregon, United States

North Carolina Retina Associates; 🇺🇸 Wake Forest, North Carolina, United States

Retina Consultants of TEXAS- Newcastle; 🇺🇸 Bellaire, Texas, United States

Carolina Center for Sight; 🇺🇸 Florence, South Carolina, United States

Mt. Olympus Research-Garcia; 🇺🇸 Houston, Texas, United States

Retina Consultants of TEXAS - Round Rock; 🇺🇸 Round Rock, Texas, United States

Lions Eye Institute; 🇦🇺 Nedlands, Australia

Emerson Clinical Research Institute; 🇺🇸 Falls Church, Virginia, United States

The Alfred Hospital; 🇦🇺 Melbourne, Australia

Vizus Eood; 🇧🇬 Gorna Oryahovitsa, Veliko Tarnovo, Bulgaria

Mhat Dr. Stamen Iliev Ad; 🇧🇬 Montana, Bulgaria

Medical Center Dar Plovdiv Ltd; 🇧🇬 Plovdiv, Bulgaria

Umhat Lozenets Ead; 🇧🇬 Sofia, Bulgaria

University First Mhat - Sofia Sv. Joan Krastitel Ead; 🇧🇬 Sofia, Bulgaria

Medical Center Vereya Ltd; 🇧🇬 Stara Zagora, Bulgaria

Specialized Hospital For Active Treatment in Ophthalmology - Varna; 🇧🇬 Varna, 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

Weifang Eye Hospital; 🇨🇳 Weifang, Shandong, China

The People's Hospital of Ningxia Hui Autonomous Region; 🇨🇳 Yinchuan, Ningxia, China

Centre Hospitalier Universitaire Amiens-Picardie Service D'Ophthalmologie Amiens France; 🇫🇷 Amiens, France

Eye Clinic Sulzbach; 🇩🇪 Sulzbach, Germany

Oftex Ocni Klinika; 🇨🇿 Pardubice, Czechia

Shanxi Eye Hospital; 🇨🇳 Taiyuan, Shanxi, China

University Eye Clinic Centre Hospitalier Creteil Paris France; 🇫🇷 Paris, France

Ukb University of Bonn; 🇩🇪 Bonn, Germany

University Hospital Freiburg; 🇩🇪 Freiburg, Germany

Justus Liebig University Giessen; 🇩🇪 Giessen, Germany

Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika; 🇭🇺 Pecs, Hungary

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Johannes Gutenberg University Mainz; 🇩🇪 Mainz, Germany

Bajcsy-Zsilinszky Korhaz Es Rendelointezet; 🇭🇺 Budapest, Hungary

Szegedi Tudomanyegyetem Aok Szakk; 🇭🇺 Szeged, Hungary

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

Riga East University Hospital; 🇱🇻 Riga, Latvia

P Stradina Clinical University Hospital; 🇱🇻 Riga, Latvia

Nzoz E-Vita; 🇵🇱 Bialystok, Podlaskie, Poland

Centrum Klinicke Oftalmologie S.R.O; 🇵🇱 Katowice, Poland

Oftalmika Sp Z.O.O; 🇵🇱 Bydgoszcz, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline; 🇵🇱 Lublin, Poland

Caminomed Wojciech Jedrzejewski; 🇵🇱 Tarnowskie Góry, Poland

Centrum Medyczne Uno-Med; 🇵🇱 Tarnów, Poland

Szpital SW Wojciecha; 🇵🇱 Poznan, Poland

Nzoz Optimed; 🇵🇱 Warsaw, Poland

National University Hospital; 🇸🇬 Singapore, Singapore

Zvezdara University Medical Center; 🇷🇸 Belgrade, Serbia

Centrum Medyczne Piasta 47; 🇵🇱 Walbrzych, Poland

Retina Okulistyka Sp.Z O.O.Sp.K.; 🇵🇱 Warszawa, Poland

Ocna Klinika Szu F.D.R.Banska Bystrica; 🇸🇰 Banská Bystrica, Slovakia

Nemocnica Poprad As Oftalmologicke Oddelenie Jzs; 🇸🇰 Poprad, Slovakia

Fakultna Nemocnica Nitra; 🇸🇰 Nitra, Slovakia

Nemocnica S Poliklinikou Trebisov A.S. Ocne Oddelenie Jzs; 🇸🇰 Trebišov, Slovakia

Fakultna Nemocnica Trencin; 🇸🇰 Trenčianske Teplice, Slovakia

VISSUM; 🇪🇸 Alicante, Spain

Fakultna Nemocnica S Poliklinikou Zilina; 🇸🇰 Žilina, Slovakia

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

Hospital La Arruzafa; 🇪🇸 Cordoba, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Majadahonda, Spain

Clinica Universitario de Navarra; 🇪🇸 Pamplona, Spain

Hospital Universitario Donostia; 🇪🇸 San Sebastián, Spain

Omiq Hospital General de Catalunya; 🇪🇸 Sant Cugat Del Valles, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, 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

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

The University of Chicago; 🇺🇸 Chicago, Illinois, United States

Retina Consultants of Southern Colorado; 🇺🇸 Colorado Springs, Colorado, United States

Illinois Retina Associates; 🇺🇸 Oak Park, Illinois, United States

South Coast Retina Center; 🇺🇸 Long Beach, California, United States

Florida Retina Institute-Orlando; 🇺🇸 Orlando, Florida, United States

Butchertown Clinical Trials; 🇺🇸 Louisville, Kentucky, United States

Retina Consultants of Charleston: Charleston Neuroscience Institute; 🇺🇸 Charleston, South Carolina, United States