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N

North Carolina Retina Associates | Wake Forest

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

H

Henlius Pharmaceuticals

Status and phase

Active, not recruiting
Phase 3

Conditions

Age Related Macular Degeneration

Treatments

Drug: HLX04-O
Drug: ranibizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT04740671
HLX04-O-wAMD

Details and patient eligibility

About

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

Full 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.

Enrollment

388 estimated patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

388 participants in 2 patient groups

HLX04-O
Experimental group
Description:
Biologic recombinant anti-VEGF humanized monoclonal antibody
Treatment:
Drug: HLX04-O
Ranibizumab
Active Comparator group
Description:
Biologic anti-VEGF recombinant humanized monoclonal antibody fragment
Treatment:
Drug: ranibizumab

Trial contacts and locations

129

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Central trial contact

Qi Jin, Bachelor

Data sourced from clinicaltrials.gov

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