Clinical trial NCT04740671: A Phase 3 Study to 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: 2021-02-05
Enrollment: 410
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 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.

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.

Primary outcomes:
measure: Mean change from baseline in BCVA at at Week 36
timeFrame: up to at Week 36
Secondary outcomes:
measure: Key Secondary Outcome : Mean change from baseline in BCVA at Week 48.
timeFrame: up to Week 48
measure: Mean change in BCVA over time
timeFrame: up to Week 48
measure: Proportion of patients gaining at least 15 letters in the BCVA at Week 12, 24, 36 and 48
timeFrame: up to Week 12, 24, 36 and 48
measure: Proportion of patients gaining at least 10 letters in the BCVA at Week 12, 24, 36 and 48
timeFrame: up to Week 12, 24, 36 and 48
measure: Proportion of patients gaining at least 5 letters in the BCVA at Week 12, 24, 36 and 48
timeFrame: up to Week 12, 24, 36 and 48
measure: • 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)
timeFrame: up to Week 12, 36 and 48
measure: • Mean change from baseline in CRT on OCT at Week 12, 24, 36 and 48 (as measured by the Reading Center)
timeFrame: up to week 12, 24, 36 and 48
measure: Change from baseline in NEI VFQ-25 scale score at Week 12, 36, and 48.
timeFrame: up to Week 12, 36, and 48
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Associated Retina Consultants-Gilbert
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants-Phoenix
state: Arizona
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Glendale
country: United States
facility: Global Research Management
state: California
city: Huntington Beach
country: United States
facility: Atlantis Eyecare, VMR Institute
state: California
city: Huntington Beach
country: United States
facility: VMR Institute
state: California
city: Long Beach
country: United States
facility: South Coast Retina Center
state: California
city: Los Alamitos
country: United States
facility: Retina Consultants of Orange County
state: California
city: Los Angeles
country: United States
facility: MACRO Trials/ Lazar Retina
state: California
city: Torrance
country: United States
facility: East West Eye Institute
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Florida Retina Institute-Orlando
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute-Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago, IL
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Oak Park
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Lenexa
country: United States
facility: Retina Associates LLC
state: Kansas
city: Louisville
country: United States
facility: Butchertown Clinical Trials
state: Kentucky
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Edina
country: United States
facility: Retina Consultants of Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: Mississippi Retina Associates
state: Mississippi
city: Asheville
country: United States
facility: Piedmont Retina Specialists
state: North Carolina
city: Asheville
country: United States
facility: Western Carolina Retinal Associates
state: North Carolina
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Wake Forest
country: United States
facility: North Carolina Retina Associates
state: North Carolina
city: Eugene
country: United States
facility: Verum Research, LLC
state: Oregon
city: Beaufort
country: United States
facility: Retina Consultants of Charleston - Beaufort
state: South Carolina
city: Charleston
country: United States
facility: Retina Consultants of Charleston: Charleston Neuroscience Institute
state: South Carolina
city: Florence
country: United States
facility: Carolina Center for Sight
state: South Carolina
city: Nashville
country: United States
facility: Retina Consultants of Nashville
state: Tennessee
city: Bellaire
country: United States
facility: Retina Consultants of TEXAS- Newcastle
state: Texas
city: Houston
country: United States
facility: Mt. Olympus Research-Garcia
state: Texas
city: Houston
country: United States
facility: Mt. Olympus Research/Museum Eye District
state: Texas
city: Round Rock
country: United States
facility: Retina Consultants of TEXAS - Round Rock
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah, PLLC
state: Utah
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Falls Church
country: United States
facility: Emerson Clinical Research Institute
state: Virginia
city: Nedlands
country: Australia
facility: Lions Eye Institute
state: Western Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Nedlands
country: Australia
facility: Lions Eye Institute
city: Gorna Oryahovitsa
country: Bulgaria
facility: Vizus Eood
state: Veliko Tarnovo
city: Burgas
country: Bulgaria
facility: Specialized Eye Hospital For Active Treatment - Burgas Ltd
city: Montana
country: Bulgaria
facility: Mhat Dr. Stamen Iliev Ad
city: Plovdiv
country: Bulgaria
facility: Assoc. Prof. Dr. Desislava Koleva Aipsmaed Sveti Luka Eood
city: Plovdiv
country: Bulgaria
facility: Medical Center Dar Plovdiv Ltd
city: Sofia
country: Bulgaria
facility: Dcc Aleksandrovska Eood
city: Sofia
country: Bulgaria
facility: Umhat Lozenets Ead
city: Sofia
country: Bulgaria
facility: University First Mhat - Sofia Sv. Joan Krastitel Ead
city: Stara Zagora
country: Bulgaria
facility: Medical Center Vereya Ltd
city: Varna
country: Bulgaria
facility: Specialized Hospital For Active Treatment in Ophthalmology - Varna
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Shantou
country: China
facility: Joint Shangtou International Eye Center Of Shantou University And The Chinese University Of Hong Kong
state: Guangdong
city: Xinxiang
country: China
facility: The Third Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: The People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia
city: Weifang
country: China
facility: Weifang Eye Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai First Peoples's Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Eye Hospital
state: Shanxi
city: Pardubice
country: Czechia
facility: Oftex Ocni Klinika
city: Amiens
country: France
facility: Centre Hospitalier Universitaire Amiens-Picardie Service D'Ophthalmologie Amiens France
city: Paris
country: France
facility: University Eye Clinic Centre Hospitalier Creteil Paris France
city: Bonn
country: Germany
facility: Ukb University of Bonn
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Giessen
country: Germany
facility: Justus Liebig University Giessen
city: Mainz
country: Germany
facility: Johannes Gutenberg University Mainz
city: Munster
country: Germany
facility: St Franziskus Hospital Munster
city: Sulzbach
country: Germany
facility: Eye Clinic Sulzbach
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz Es Rendelointezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz Es Rendelointezet
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika
city: Pécs
country: Hungary
facility: Ganglion Orvosi Kozpont
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Aok Szakk
city: Milan
country: Italy
facility: Clinica Oculistica Ospedale Luigi Sacco, Universita' Degli Studi Di Milano
city: Milan
country: Italy
facility: Clinica Oculistica Universita Vita Salute - Irccs Ospedale San Raffaele
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli - Irccs Uoc Oculistica
city: Rome
country: Italy
facility: Irccs Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia Onlus Rome, Italy
city: Riga
country: Latvia
facility: P Stradina Clinical University Hospital
city: Riga
country: Latvia
facility: Riga East University Hospital
city: Bialystok
country: Poland
facility: Nzoz E-Vita
state: Podlaskie
city: Krakow
country: Poland
facility: Centrum Medyczne Promed
state: WA
city: Bydgoszcz
country: Poland
facility: Oftalmika Sp Z.O.O
city: Katowice
country: Poland
facility: Centrum Klinicke Oftalmologie S.R.O
city: Kraków
country: Poland
facility: Szpital SW. Rozy
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline
city: Poznan
country: Poland
facility: Szpital SW Wojciecha
city: Tarnowskie Góry
country: Poland
facility: Caminomed Wojciech Jedrzejewski
city: Tarnów
country: Poland
facility: Centrum Medyczne Uno-Med
city: Walbrzych
country: Poland
facility: Centrum Medyczne Piasta 47
city: Warsaw
country: Poland
facility: Nzoz Optimed
city: Warszawa
country: Poland
facility: Retina Okulistyka Sp.Z O.O.Sp.K.
city: Belgrade
country: Serbia
facility: Special Optalmological Hospital Belgrade
city: Belgrade
country: Serbia
facility: Zvezdara University Medical Center
city: Singapore
country: Singapore
facility: National University Hospital
city: Banská Bystrica
country: Slovakia
facility: Ocna Klinika Szu F.D.R.Banska Bystrica
city: Nitra
country: Slovakia
facility: Fakultna Nemocnica Nitra
city: Nové Zámky
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Nove Zamky Oftalmologicke Nelozkove Oddelenie
city: Poprad
country: Slovakia
facility: Nemocnica Poprad As Oftalmologicke Oddelenie Jzs
city: Trebišov
country: Slovakia
facility: Nemocnica S Poliklinikou Trebisov A.S. Ocne Oddelenie Jzs
city: Trenčianske Teplice
country: Slovakia
facility: Fakultna Nemocnica Trencin
city: Žilina
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Zilina
city: Alicante
country: Spain
facility: VISSUM
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Barcelona
country: Spain
facility: Institito de Microcirugia Ocular
city: Barcelona
country: Spain
facility: Institut Catala de La Retina
city: Burjassot
country: Spain
facility: Oftalvist Clinic
city: Cordoba
country: Spain
facility: Hospital La Arruzafa
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Oviedo
country: Spain
facility: Instituto Oftalmologico Fernandez-Vega
city: Pamplona
country: Spain
facility: Clinica Universitario de Navarra
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Sant Cugat Del Valles
country: Spain
facility: Omiq Hospital General de Catalunya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Clinica Oftalmologica Aiken
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Fisabio Oftalmologia Medica
city: Valladolid
country: Spain
facility: Hospital Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References: