Wet Age-related Macular Degeneration (wAMD) MedDRA version: 20.0 Level: LLT Classification code 10075568 Term: Wet age-related macular degeneration System Organ Class: 100000004853
Conditions
Interventions
Product Code: HLX04-O
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Recombinant Anti-VEGF Humanized Monoclonal Antibody Ophthalmic Injection
CAS Number: 216974-75-3
Current Sponsor
Sponsors
Shanghai Henlius Biotech. Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable to understand, and sign the informed consent form (ICF) which includes compliance with the requirements and restrictions. 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 the protocol. 4. Newly diagnosed, untreated, active subfoveal or juxtafoyeal CNV lesions secondary to age-related macular degeneration 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) eyes must have had 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 374
Exclusion criteria
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 with confirmation of the reading center. 2.The fellow (non study) eye needs anti-VEGF IVT injection 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 autoimmuneassociated 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 8.Equivalent spherical diopter of the study eye =-8D. 9.Estimated by the Investigator, any concurrent intraocular condition except wAMD 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 (including 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 or systemic use of corticosteroids within 3 months prior to dose 1 in the study eye. 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 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. 17.In the Investigator's judgment, there
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of HLX04-O at Week 36 compared with ranibizumab in patient's study eye with wAMD. ;Secondary Objective: To evaluate the efficacy of HLX04-O at Week 12, 24, 36 and 48 compared with ranibizumab in patient's study eye with wAMD. To evaluate the safety and tolerability of HLX04-O compared with ranibizumab in patients with wAMD. To characterize the systemic pharmacokinetics of HLX04-O IVT administration.;Primary end point(s): Mean change from baseline in best-corrected visual acuity (BCVA) at Week 36.;Timepoint(s) of evaluation of this end point: Week 36 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Mean change from baseline in BCVA at Week 12, 24 and 48; • Mean change in the BCVA over time; • Proportion of patients gaining at least 15 letters in the BCVA at Week 12, 24, 36 and 48; • Proportion of patients gaining at least 10 letters in the BCVA at Week 12, 24, 36 and 48; • Proportion of patients gaining at least 5 letters in the BCVA at Week 12, 24, 36 and 48; • Mean change from baseline in size of CNV and the total area of fluorescein leakage on FA at Week 12, 36 and 48 (as measured by the Reading Center); • Mean change from baseline in central retina thickness (CRT) on OCT at Week 12, 24, 36 and 48 (as measured by the Reading Center); • Change from baseline in NEI VFQ-25 scale score at Week 12, 36, and 48. •Percentage and severity of ocular AEs (IVT procedure related and Investigation Medication related), non-ocular AEs; laboratory abnormalities; vital sign, physical examination abnormalities, etc. • Incidence of ADAs and NAbs against HLX04-O following IVT administration. •HLX04-O serum concentrations before Dose 1, Dose 2, Dose 6, Dose 9, Dose 12 and the last visit as data permit. • HLX04-O systemic PK parameters following IVT administration of Dose 1 and Dose 4, including but not limited to: ? AUC(0-t): Area under the serum concentration-time curve during the dosage interval; ? Cmax: Maximum drug concentration; ? Cmin: Minimum drug concentration; ? Tmax: Time to Cmax; ? t1/2: Elimination half-life, as data permit; ? CL/F: Apparent total body clearance following Dose 4 at steady state ? Accumulation ratios (Dose 4/Dose 1) for AUC(0-t), Cmax and Cmin.;Timepoint(s) of evaluation of this end point: Timepoints included in above endpoints and throughout the duration of the study | — |
Countries
Australia, China, Czechia, Czech Republic, Hungary, Latvia, Poland, Russian Federation, Serbia, Singapore, Spain
Contacts
Public ContactConnie Kang
Shanghai Henlius Biotech. Inc.
Outcome results
None listed