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

NCT04740671 | Completed Phase 3 FDA Drug

• 1 other identifier: HLX04-O-wAMD
• Study Type: interventional
• Target: 410
• Locations: 15 countries
• Sites: 126

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.

Conditions

Age Related Macular Degeneration

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Key Secondary Outcome : Mean change from baseline in BCVA at Week 48.

  up to Week 48

• Mean change in BCVA over time

  up to Week 48

• 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

• 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

• 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

Study Arms (2)

HLX04-O

EXPERIMENTAL

Biologic recombinant anti-VEGF humanized monoclonal antibody

Drug: HLX04-O

Ranibizumab

ACTIVE COMPARATOR

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Drug: ranibizumab

Interventions

HLX04-O DRUG

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

HLX04-O

ranibizumab DRUG

Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Ranibizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Women or men aged ≥50 years when signing the ICF.
• In the Investigator's judgment, willing and able to complete all visits and assessments adhering to the prohibitions and restrictions specified in this protocol.
• 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.
• 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
• The BCVA letters between 24 and 73, inclusive, in the study eye, using Early Treatment Diabetic Retinopathy Study (ETDRS) charts.
• Participants' fellow (non-study) eye must have a BCVA of 24 letters or better.
• Clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm the diagnosis.

You may not qualify if:

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

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (126)

Associated Retina Consultants-Gilbert

Gilbert, Arizona, 85297, United States

Location

Associated Retina Consultants-Phoenix

Phoenix, Arizona, 85020, United States

Location

Retina Consultants of Orange County

Fullerton, California, 92835, United States

Location

Global Research Management

Glendale, California, 91204, United States

Location

Atlantis Eyecare, VMR Institute

Huntington Beach, California, 92647, United States

Location

VMR Institute

Huntington Beach, California, 92647, United States

Location

South Coast Retina Center

Long Beach, California, 90807, United States

Location

Retina Consultants of Orange County

Los Alamitos, California, 90720, United States

Location

MACRO Trials/ Lazar Retina

Los Angeles, California, 90048, United States

Location

East West Eye Institute

Torrance, California, 90505, United States

Location

Retina Consultants of Southern Colorado

Colorado Springs, Colorado, 80909, United States

Location

Florida Retina Institute-Orlando

Jacksonville, Florida, 32216, United States

Location

Florida Retina Institute-Orlando

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Center for Retina and Macular Disease

Winter Haven, Florida, 33880, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

The University of Chicago, IL

Chicago, Illinois, 60637, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Illinois Retina Associates

Oak Park, Illinois, 60304, United States

Location

Retina Associates LLC

Lenexa, Kansas, 66215, United States

Location

Butchertown Clinical Trials

Louisville, Kentucky, 40206, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Retina Consultants of Minnesota

Edina, Minnesota, 55435, United States

Location

VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Mississippi Retina Associates

Jackson, Mississippi, 39202, United States

Location

Piedmont Retina Specialists

Asheville, North Carolina, 27103, United States

Location

Western Carolina Retinal Associates

Asheville, North Carolina, 28803, United States

Location

Graystone Eye

Hickory, North Carolina, 28602, United States

Location

North Carolina Retina Associates

Wake Forest, North Carolina, 27332, United States

Location

Verum Research, LLC

Eugene, Oregon, 97401, United States

Location

Retina Consultants of Charleston - Beaufort

Beaufort, South Carolina, 29902, United States

Location

Retina Consultants of Charleston: Charleston Neuroscience Institute

Charleston, South Carolina, 29414, United States

Location

Carolina Center for Sight

Florence, South Carolina, 29501, United States

Location

Retina Consultants of Nashville

Nashville, Tennessee, 37203, United States

Location

Retina Consultants of TEXAS- Newcastle

Bellaire, Texas, 77401, United States

Location

Mt. Olympus Research-Garcia

Houston, Texas, 77015, United States

Location

Mt. Olympus Research/Museum Eye District

Houston, Texas, 77015, United States

Location

Retina Consultants of TEXAS - Round Rock

Round Rock, Texas, 78681, United States

Location

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

Location

Retina Associates of Utah, PLLC

Salt Lake City, Utah, 84107, United States

Location

Rocky Mountain Retina Consultants

Salt Lake City, Utah, 84107, United States

Location

Emerson Clinical Research Institute

Falls Church, Virginia, 22042, United States

Location

Lions Eye Institute

Nedlands, Western Australia, WA 6009, Australia

Location

The Alfred Hospital

Melbourne, Australia

Location

Lions Eye Institute

Nedlands, Australia

Location

Mhat Dr. Stamen Iliev Ad

Montana, Montana, Bulgaria

Location

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

Plovdiv, Plovdiv, Bulgaria

Location

Dcc Aleksandrovska Eood

Sofia, Sofia, Bulgaria

Location

Umhat Lozenets Ead

Sofia, Sofia, Bulgaria

Location

University First Mhat - Sofia Sv. Joan Krastitel Ead

Sofia, Sofia, Bulgaria

Location

Specialized Hospital For Active Treatment in Ophthalmology - Varna

Varna, Varna, Bulgaria

Location

Vizus Eood

Gorna Oryahovitsa, Veliko Tarnovo, Bulgaria

Location

Specialized Eye Hospital For Active Treatment - Burgas Ltd

Burgas, Bulgaria

Location

Medical Center Dar Plovdiv Ltd

Plovdiv, Bulgaria

Location

Medical Center Vereya Ltd

Stara Zagora, Bulgaria

Location

Lanzhou University Second Hospital

Lanzhou, Gansu, China

Location

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

Shantou, Guangdong, China

Location

The Third Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, China

Location

First Hospital of Jilin University

Changchun, Jilin, China

Location

The People's Hospital of Ningxia Hui Autonomous Region

Yinchuan, Ningxia, China

Location

Weifang Eye Hospital

Weifang, Shandong, China

Location

Shanghai First Peoples's Hospital

Shanghai, Shanghai Municipality, China

Location

Shanxi Eye Hospital

Taiyuan, Shanxi, China

Location

Oftex Ocni Klinika

Pardubice, Czechia

Location

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

Amiens, France

Location

University Eye Clinic Centre Hospitalier Creteil Paris France

Paris, France

Location

Ukb University of Bonn

Bonn, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

Justus Liebig University Giessen

Giessen, Germany

Location

Johannes Gutenberg University Mainz

Mainz, Germany

Location

St Franziskus Hospital Munster

Münster, Germany

Location

Eye Clinic Sulzbach

Sulzbach, Germany

Location

Bajcsy-Zsilinszky Korhaz Es Rendelointezet

Budapest, Budapest, Hungary

Location

Semmelweis Egyetem

Budapest, Hungary

Location

Markhot Ferenc Oktatokorhaz Es Rendelointezet

Eger, Hungary

Location

Ganglion Orvosi Kozpont

Pécs, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika

Pécs, Hungary

Location

Szegedi Tudomanyegyetem Aok Szakk

Szeged, Hungary

Location

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

Rome, Rome, Italy

Location

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

Milan, Italy

Location

Clinica Oculistica Universita Vita Salute - Irccs Ospedale San Raffaele

Milan, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli - Irccs Uoc Oculistica

Rome, Italy

Location

P Stradina Clinical University Hospital

Riga, Latvia

Location

Riga East University Hospital

Riga, Latvia

Location

Nzoz E-Vita

Bialystok, Podlaskie Voivodeship, Poland

Location

Centrum Medyczne Promed

Krakow, WA, Poland

Location

Oftalmika Sp Z.O.O

Bydgoszcz, Poland

Location

Centrum Klinicke Oftalmologie S.R.O

Katowice, Poland

Location

Szpital SW. Rozy

Krakow, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline

Lublin, Poland

Location

Szpital SW Wojciecha

Poznan, Poland

Location

Caminomed Wojciech Jedrzejewski

Tarnowskie Góry, Poland

Location

Centrum Medyczne Uno-Med

Tarnów, Poland

Location

Nzoz Optimed

Warsaw, Poland

Location

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

Warsaw, Poland

Location

Centrum Medyczne Piasta 47

Wałbrzych, Poland

Location

Special Optalmological Hospital Belgrade

Belgrade, Serbia

Location

Zvezdara University Medical Center

Belgrade, Serbia

Location

National University Hospital

Singapore, Singapore

Location

Ocna Klinika Szu F.D.R.Banska Bystrica

Banská Bystrica, Slovakia

Location

Fakultna Nemocnica Nitra

Nitra, Slovakia

Location

Fakultna Nemocnica S Poliklinikou Nove Zamky Oftalmologicke Nelozkove Oddelenie

Nové Zámky, Slovakia

Location

Nemocnica Poprad As Oftalmologicke Oddelenie Jzs

Poprad, Slovakia

Location

Nemocnica S Poliklinikou Trebisov A.S. Ocne Oddelenie Jzs

Trebišov, Slovakia

Location

Fakultna Nemocnica Trencin

Trenčianske Teplice, Slovakia

Location

Fakultna Nemocnica S Poliklinikou Zilina

Žilina, Slovakia

Location

VISSUM

Alicante, Spain

Location

Centro de Oftalmologia Barraquer

Barcelona, Spain

Location

Hospital Universitari Vall D Hebron

Barcelona, Spain

Location

Institito de Microcirugia Ocular

Barcelona, Spain

Location

Institut Catala de La Retina

Barcelona, Spain

Location

Oftalvist Clinic

Burjassot, Spain

Location

Hospital La Arruzafa

Córdoba, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Instituto Oftalmologico Fernandez-Vega

Oviedo, Spain

Location

Clinica Universitario de Navarra

Pamplona, Spain

Location

Hospital Universitario Donostia

San Sebastián, Spain

Location

Omiq Hospital General de Catalunya

Sant Cugat del Vallès, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Clinica Oftalmologica Aiken

Valencia, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, Spain

Location

Fisabio Oftalmologia Medica

Valencia, Spain

Location

Hospital Rio Hortega

Valladolid, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 5, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BU (10); SG (1); DE (6); SE (2); US (42); IT (4); LA (2); CZ (1); AU (3); FR (2); HU (6); PL (12); SL (7); CN (8); ES (20)