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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04740671




Registration number
NCT04740671
Ethics application status
Date submitted
2/02/2021
Date registered
5/02/2021
Date last updated
17/04/2024

Titles & IDs
Public title
A Phase 3 Study to Compare the Efficacy and Safety of HLX04-O With Ranibizumab in Subjects With wAMD
Scientific 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)
Secondary ID [1] 0 0
HLX04-O-wAMD
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age Related Macular Degeneration 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HLX04-O
Treatment: Drugs - ranibizumab

Experimental: HLX04-O - Biologic recombinant anti-VEGF humanized monoclonal antibody

Active comparator: Ranibizumab - Biologic anti-VEGF recombinant humanized monoclonal antibody fragment


Treatment: Drugs: HLX04-O
Biologic recombinant anti-VEGF humanized monoclonal antibody, developed by Shanghai Henlius Biotech, Inc.

Treatment: Drugs: ranibizumab
Biologic anti-VEGF recombinant humanized monoclonal antibody fragment
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean change from baseline in BCVA at at Week 36
Timepoint [1] 0 0
up to at Week 36
Secondary outcome [1] 0 0
Key Secondary Outcome : Mean change from baseline in BCVA at Week 48.
Timepoint [1] 0 0
up to Week 48
Secondary outcome [2] 0 0
Mean change in BCVA over time
Timepoint [2] 0 0
up to Week 48
Secondary outcome [3] 0 0
Proportion of patients gaining at least 15 letters in the BCVA at Week 12, 24, 36 and 48
Timepoint [3] 0 0
up to Week 12, 24, 36 and 48
Secondary outcome [4] 0 0
Proportion of patients gaining at least 10 letters in the BCVA at Week 12, 24, 36 and 48
Timepoint [4] 0 0
up to Week 12, 24, 36 and 48
Secondary outcome [5] 0 0
Proportion of patients gaining at least 5 letters in the BCVA at Week 12, 24, 36 and 48
Timepoint [5] 0 0
up to Week 12, 24, 36 and 48
Secondary outcome [6] 0 0
• 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)
Timepoint [6] 0 0
up to Week 12, 36 and 48
Secondary outcome [7] 0 0
• Mean change from baseline in CRT on OCT at Week 12, 24, 36 and 48 (as measured by the Reading Center)
Timepoint [7] 0 0
up to week 12, 24, 36 and 48
Secondary outcome [8] 0 0
Change from baseline in NEI VFQ-25 scale score at Week 12, 36, and 48.
Timepoint [8] 0 0
up to Week 12, 36, and 48

Eligibility
Key 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.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
388
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Lions Eye Institute - Nedlands
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
WA 6009 - Nedlands
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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United States of America
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Florida
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Georgia
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United States of America
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Illinois
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Kansas
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United States of America
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Kentucky
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Maryland
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Minnesota
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Mississippi
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North Carolina
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Oregon
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South Carolina
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Tennessee
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Texas
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Utah
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United States of America
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Virginia
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Bulgaria
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Veliko Tarnovo
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Bulgaria
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Burgas
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Bulgaria
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Montana
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Bulgaria
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Plovdiv
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Sofia
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Bulgaria
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Stara Zagora
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Varna
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China
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Gansu
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China
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Guangdong
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China
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Henan
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China
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Jilin
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China
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Ningxia
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China
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Shandong
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China
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Shanghai
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China
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Shanxi
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Czechia
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Pardubice
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France
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Amiens
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France
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Paris
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Germany
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Bonn
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Germany
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Freiburg
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Germany
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Giessen
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Germany
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Mainz
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Germany
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Munster
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Germany
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Sulzbach
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Budapest
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Eger
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Pecs
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Pécs
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Szeged
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Riga
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Podlaskie
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WA
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Bydgoszcz
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Tarnów
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Walbrzych
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Warsaw
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Warszawa
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Serbia
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Belgrade
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Singapore
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Singapore
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Slovakia
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Banská Bystrica
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Slovakia
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Nitra
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Slovakia
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Nové Zámky
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Slovakia
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Poprad
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Slovakia
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Trebišov
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Slovakia
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Trencianske Teplice
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Slovakia
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Žilina
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Burjassot
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Spain
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Cordoba
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Spain
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Madrid
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Spain
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Majadahonda
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Spain
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Oviedo
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Spain
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Pamplona
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Spain
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San Sebastián
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Spain
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Sant Cugat Del Valles
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Spain
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Sevilla
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Spain
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Valencia
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Spain
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Valladolid
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Spain
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Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Shanghai Henlius Biotech
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04740671
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04740671