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

Age Related Macular Degeneration Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04740671
• Other study ID #: HLX04-O-wAMD
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: Shanghai Henlius Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 388
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Age Related Macular Degeneration
• Macular Degeneration

Intervention

Drug:
• HLX04-O
Biologic recombinant anti-VEGF humanized monoclonal antibody, developed by Shanghai Henlius Biotech, Inc.
• ranibizumab
Biologic anti-VEGF recombinant humanized monoclonal antibody fragment

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne
Australia	Lions Eye Institute	Nedlands
Australia	Lions Eye Institute	Nedlands	Western Australia
Bulgaria	Specialized Eye Hospital For Active Treatment - Burgas Ltd	Burgas
Bulgaria	Vizus Eood	Gorna Oryahovitsa	Veliko Tarnovo
Bulgaria	Mhat Dr. Stamen Iliev Ad	Montana
Bulgaria	Assoc. Prof. Dr. Desislava Koleva Aipsmaed Sveti Luka Eood	Plovdiv
Bulgaria	Medical Center Dar Plovdiv Ltd	Plovdiv
Bulgaria	Dcc Aleksandrovska Eood	Sofia
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
China	First Hospital of Jilin University	Changchun	Jilin
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	Shanghai First Peoples's Hospital	Shanghai	Shanghai
China	Joint Shangtou International Eye Center Of Shantou University And The Chinese University Of Hong Kong	Shantou	Guangdong
China	Shanxi Eye Hospital	Taiyuan	Shanxi
China	Weifang Eye Hospital	Weifang	Shandong
China	The Third Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	The People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia
Czechia	Oftex Ocni Klinika	Pardubice
France	Centre Hospitalier Universitaire Amiens-Picardie Service D'Ophthalmologie Amiens France	Amiens
France	University Eye Clinic Centre Hospitalier Creteil Paris France	Paris
Germany	Ukb University of Bonn	Bonn
Germany	University Hospital Freiburg	Freiburg
Germany	Justus Liebig University Giessen	Giessen
Germany	Johannes Gutenberg University Mainz	Mainz
Germany	St Franziskus Hospital Munster	Munster
Germany	Eye Clinic Sulzbach	Sulzbach
Hungary	Bajcsy-Zsilinszky Korhaz Es Rendelointezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Markhot Ferenc Oktatokorhaz Es Rendelointezet	Eger
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont - Szemeszeti Klinika	Pecs
Hungary	Ganglion Orvosi Kozpont	Pécs
Hungary	Szegedi Tudomanyegyetem Aok Szakk	Szeged
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	Irccs Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia Onlus Rome, Italy	Rome
Latvia	P Stradina Clinical University Hospital	Riga
Latvia	Riga East University Hospital	Riga
Poland	Nzoz E-Vita	Bialystok	Podlaskie
Poland	Oftalmika Sp Z.O.O	Bydgoszcz
Poland	Centrum Klinicke Oftalmologie S.R.O	Katowice
Poland	Centrum Medyczne Promed	Krakow	WA
Poland	Szpital SW. Rozy	Kraków
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 W Lubline	Lublin
Poland	Szpital SW Wojciecha	Poznan
Poland	Centrum Medyczne Uno-Med	Tarnów
Poland	Caminomed Wojciech Jedrzejewski	Tarnowskie Góry
Poland	Centrum Medyczne Piasta 47	Walbrzych
Poland	Nzoz Optimed	Warsaw
Poland	Retina Okulistyka Sp.Z O.O.Sp.K.	Warszawa
Serbia	Special Optalmological Hospital Belgrade	Belgrade
Serbia	Zvezdara University Medical Center	Belgrade
Singapore	National University Hospital	Singapore
Slovakia	Fakultna Nemocnica S Poliklinikou Zilina	Žilina
Slovakia	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	Trencianske Teplice
Spain	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	Cordoba
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 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
United States	Piedmont Retina Specialists	Asheville	North Carolina
United States	Western Carolina Retinal Associates	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Retina Consultants of Charleston - Beaufort	Beaufort	South Carolina
United States	Retina Consultants of TEXAS- Newcastle	Bellaire	Texas
United States	Retina Consultants of Charleston: Charleston Neuroscience Institute	Charleston	South Carolina
United States	The University of Chicago	Chicago	Illinois
United States	The University of Chicago, IL	Chicago	Illinois
United States	Retina Consultants of Southern Colorado	Colorado Springs	Colorado
United States	Retina Consultants of Minnesota	Edina	Minnesota
United States	Verum Research, LLC	Eugene	Oregon
United States	Emerson Clinical Research Institute	Falls Church	Virginia
United States	Carolina Center for Sight	Florence	South Carolina
United States	Retina Consultants of Orange County	Fullerton	California
United States	Associated Retina Consultants-Gilbert	Gilbert	Arizona
United States	Global Research Management	Glendale	California
United States	Cumberland Valley Retina Consultants	Hagerstown	Maryland
United States	Graystone Eye	Hickory	North Carolina
United States	Mt. Olympus Research-Garcia	Houston	Texas
United States	Mt. Olympus Research/Museum Eye District	Houston	Texas
United States	Atlantis Eyecare, VMR Institute	Huntington Beach	California
United States	VMR Institute	Huntington Beach	California
United States	Mississippi Retina Associates	Jackson	Mississippi
United States	Florida Retina Institute-Orlando	Jacksonville	Florida
United States	Retina Associates LLC	Lenexa	Kansas
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	Butchertown Clinical Trials	Louisville	Kentucky
United States	Retina Consultants of Nashville	Nashville	Tennessee
United States	Illinois Retina Associates	Oak Park	Illinois
United States	Florida Retina Institute-Orlando	Orlando	Florida
United States	Associated Retina Consultants-Phoenix	Phoenix	Arizona
United States	Retina Consultants of TEXAS - Round Rock	Round Rock	Texas
United States	VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota	Saint Louis Park	Minnesota
United States	Retina Associates of Utah, PLLC	Salt Lake City	Utah
United States	Rocky Mountain Retina Consultants	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
United States	Retina Consultants of Texas	The Woodlands	Texas
United States	East West Eye Institute	Torrance	California
United States	North Carolina Retina Associates	Wake Forest	North Carolina
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Mean change in BCVA over time	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	up to Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	• 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
Secondary	• 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
Secondary	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