A Phase 3 Two-part Study of the Efficacy and Safety of HLX04-O in Subjects With Wet Age-related Macular Degeneration

• Status: Recruiting
• Trial end date: 2023-06-14
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate the efficacy, safety, tolerability, and pharmacokinetics of HLX04-O administered monthly, compared with ranibizumab monthly, in participants with neovascular age-related macular degeneration (nAMD).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Henlius Biotech
• Treatments: Ranibizumab

Criteria

Inclusion Criteria:

1. Capable to read, understand, and sign the informed consent form (ICF) as described in Section 10.1.3 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. Infertile women or men must 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 must meet either of the following ones: 1) women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of the study intervention, and should not breastfeed; 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 include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices (IUDs), and copper IUDs.

5. Newly diagnosed, angiographically documented, previously untreated, active subfoveal 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. Only one eye will be enrolled as the study eye in the study. If both eyes are eligible, the participant and study ophthalmologist will select the study eye for entry (usually a severe eye).

6. The total lesion area (including bleeding, scar and neovascularization) of the study eye ≤12 disc area (DA) with confirmation of the reading center before randomization and meet the requirements of fundus photography.

7. The BCVA by E-ETDRS score for the study eye must be between 20/40 and 20/320 (Snellen equivalent).

Exclusion Criteria:

1. Macular-related retinal pigment epithelial tears in the study eye, fibrosis or atrophy involving the center of the fovea, or CNV due to other causes in either eye (e.g., ocular histoplasmosis, trauma, or pathological myopia, etc.) on FA with confirmation of the reading center.

2. The area of subretinal hemorrhage involving fovea ≥50% of the total lesion area or >1 DA (2.54 mm2) in size in the study eye.

3. Aphakia (except intraocular lens) or posterior capsular rupture of the lens (except yttrium aluminium-garnet (YAG) laser postcapsulorhexis after intraocular lens implantation ≥30 days prior to first dose) in the study eye.

4. Active or recent (28 days prior to randomization) intraocular, extraocular or periocular infection (including conjunctivitis, keratitis, scleral or endophthalmitis), or history of idiopathic or autoimmune-associated uveitis in either eye.

5. Current vitreous hemorrhage in the study eye.

6. Corneal dystrophy or history of corneal transplantation, scleral softening or history of scleral softening, history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) 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. Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss within 1 year estimated by the Investigator.

10. Any concurrent intraocular condition in the fellow eye that may require anti VEGF therapy within 3 months after randomization estimated by the Investigator. No other anti VEGF treatments than HLX04-O or ranibizumab as per treatment arm are allowed for both eyes during the study period.

11. Previous treatment with AMD therapy in the study eye.

12. Previous systemic anti-VEGF therapy or IVT injection of any anti-VEGF drug into either eye.

13. Underwent internal eye surgery (including cataract extraction, vitrectomy, laser photocoagulation in macular area, etc.) within 90 days, or external eye surgery within 30 days before the first dose in the study eye.

14. Treated with corticosteroids either intraocular or systemic within 90 days or peripherally within 30 days before the first dose in the study eye.

15. Participated in any drug (other than vitamins and minerals) or device clinical trials within 30 days before the first dose and have used the test drug or received device treatment.

16. 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.

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 screening, uncontrolled hypertension (systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg), etc.).

18. 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.

19. Current treatment for active systemic infection, or history of recurrent significant infections.

20. Known active or suspected autoimmune diseases, requiring systemic immunosuppressive therapy.

21. Hepatitis B (hepatitis B virus antigen [HBsAg] positive, and hepatitis B virus [HBV] deoxyribonucleic acid [DNA] test result suggests viral replication); hepatitis C (hepatitis C virus [HCV] antibody positive, and HCV ribonucleic acid [RNA] test result suggests viral replication); participants with co-infection with hepatitis B and C (HBsAg and HCV antibody positive). Positive for syphilis screening test human immunodeficiency virus (HIV) infection or positive for HIV screening test.

22. Known allergy to any component of the study intervention or history of allergy to fluorescein or indocyanine green.

23. In the Investigator's judgment, other conditions considered not amenable to this study.

24. Participant who has been diagnosed to be COVID-19 within 14 days prior to screening.