Phase 3 Trial Comparing Efficacy, Safety, and Immunogenicity of Aflibercept (RBS-001) Versus Aflibercept in Neovascular Age-Related Macular Degeneration
- Trial ID
- 2023-509206-29-00
- Protocol
- PD-CP-Y1
- Sponsor
- Rophibio Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 clinical trial is to demonstrate the **equivalence** of RBS-001 and Eylea® in terms of Best Corrected Visual Acuity (BCVA) change from baseline, as measured by the ETDRS letter score at 8 weeks post-treatment. This is clinically relevant as it aims to establish RBS-001 as a comparable treatment option to Eylea® for patients with **neovascular age-related macular degeneration (nAMD)**, potentially expanding therapeutic choices for this condition.
Secondary objectives include:
- Evaluating other efficacy parameters of RBS-001 compared to Eylea® at each visit post-treatment versus baseline.
- Assessing the safety and tolerability of RBS-001 in comparison with Eylea®.
- Evaluating the immunogenicity of RBS-001 relative to Eylea®.
Participants
The clinical trial involves a total of **145 participants** diagnosed with **neovascular age-related macular degeneration (nAMD)**. The study population includes both male and female subjects aged **50 years and older**. Participants were selected based on specific criteria, including the presence of an active choroidal neovascularization (CNV) lesion secondary to age-related macular degeneration in the study eye, confirmed by fluorescein angiography and optical coherence tomography. The trial does not involve a vulnerable population. Participants are required to have a best-corrected visual acuity (BCVA) of 34 to 73 letters, as measured by the ETDRS letter score, at both screening and baseline visits. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensured that individuals voluntarily decided to participate after being fully informed and providing written consent to comply with study instructions.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy**, safety, tolerability, and immunogenicity of RBS-001 compared to Eylea® in subjects with **neovascular age-related macular degeneration** (nAMD). This is a Phase III, randomized, double-blind, controlled study. The trial aims to demonstrate the equivalence of RBS-001 and Eylea® in terms of best-corrected visual acuity (BCVA) change from baseline, measured by the ETDRS letter score at 8 weeks post-treatment. The study is expected to commence recruitment on May 10, 2024, and conclude by April 4, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥ 50 years), presence of active choroidal neovascularization (CNV) lesions, and specific BCVA scores. The trial will include multiple follow-up visits at weeks 4, 8, 12, 16, 20, and 24, with assessments continuing up to 52 weeks. The primary endpoint is the change in BCVA at 8 weeks, while secondary endpoints include BCVA changes at all visits, proportion of subjects with significant BCVA changes, and changes in central subfield thickness (CST) and CNV area.
The expected duration of participant involvement is up to 52 weeks. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The investigational product, RBS-001, and the comparator, Eylea®, will be administered via intravitreal injection, while fluorescein sodium will be used as an auxiliary diagnostic agent via intravenous injection. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **Aflibercept**, an experimental medication identified by the sponsor product code RBS-001. This medication is provided as a **solution for intravitreal injection** and is manufactured by Rophibio Inc. The active substance, Aflibercept, is a protein of non-human origin, specifically an immunoglobulin binding to the human VEGF receptor. The maximum daily dose is 2 mg, with a total maximum dose of 16 mg over a treatment period of 48 weeks. The route of administration is intravitreal, and the medication is administered at a frequency determined by the study protocol. Participant compliance is monitored through regular assessments and documentation of dosing schedules.
The comparator treatment in this trial is Eylea, a commercially available formulation of **Aflibercept** produced by Bayer AG. Eylea is also provided as a **solution for injection** and is administered intravitreally. The dosage and administration schedule for Eylea mirror those of the experimental medication, with a maximum daily dose of 2 mg and a total maximum dose of 16 mg over 48 weeks. This ensures a direct comparison of efficacy, safety, and tolerability between the experimental and comparator treatments.
Additionally, **Fluorescein Sodium** is used as an auxiliary treatment in the trial. It is a diagnostic stain used for fluorescence angiography, provided as a **solution for injection**. The active substance, Fluorescein Sodium, is of chemical origin and is administered intravenously. The maximum daily dose is 500 mg, with a total maximum dose of 500 mg over a treatment period of 3 days. This auxiliary treatment aids in the diagnostic evaluation of participants during the trial.
Efficacy
The efficacy of the investigational product RBS-001 will be assessed in a Phase 3 clinical trial comparing it to Eylea® in subjects with **neovascular age-related macular degeneration**. The primary endpoint for evaluating efficacy is the change from baseline in Best Corrected Visual Acuity (BCVA) measured by the ETDRS letter score at 8 weeks post-treatment. Secondary endpoints include changes in BCVA at all visits post-treatment, analyzed using a Mixed Model for Repeated Measures (MMRM) with data collected at Weeks 4, 8, 12, 16, 20, and 24. Additional secondary endpoints involve the proportion of subjects with significant changes in BCVA (≥5, ≥10, and ≥15 letters) from baseline at all visits, changes in Central Subfield Thickness (CST) measured by Optical Coherence Tomography (OCT), and the presence of intraretinal or subretinal fluid as assessed by OCT at each time point within 52 weeks post-treatment.
Further assessments include changes in the choroidal neovascularization (CNV) area and the proportion of subjects with leakage, both evaluated by fluorescein angiography (FA) at 24 and 52 weeks post-treatment compared to screening. The trial will utilize validated tools such as the ETDRS letter score for BCVA and OCT for CST and fluid assessments. These efficacy parameters will be systematically measured and analyzed to determine the equivalence of RBS-001 to Eylea® in improving visual outcomes in the study population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 50 years at screening
- Individuals with active CNV lesion secondary to AMD in the study eye, proven by fluorescein angiography (FA) and confirmed by the central reading center during the screening period
- Individuals with CNV area in the study eye accounting for ≥ 50% of the total lesion, including macular hemorrhage, scar, atrophy, fibrosis and neovascularization, proven by FA and confirmed by the central reading center during the screening period
- Individuals with intraretinal or subretinal fluid in the study eye due to active CNV, proven by optical coherence tomography (OCT) and confirmed by the central reading center during the screening period
- Individuals with BCVA of 34 to 73 letters measured by ETDRS letter score at the screening and baseline visits in the study eye
- Individuals who voluntarily decide to participate in the clinical study after being fully informed of the details of the clinical study and who provide written consent to comply with the study instructions during the clinical study
Exclusion Criteria
- 1.Individuals whose study eye lesion meets any of the following criteria (to be confirmed by the central reading center during the screening period) Item Criterion Total lesion* size > 23 mm2 [9 disc areas (DAs)] (Must be proven by FA) Subretinal hemorrhage (or subfoveal hemorrhage) ≥ 50% of the total lesion* [≥ 1 DA (In the case of subfoveal hemorrhage, fovea must be surrounded 270 degrees by visible CNV.)] Scar or fibrosis ≥ 50% of the total lesion*or Scar, fibrosis, or atrophy involving the center of the fovea Retinal pigment epithelial tears or rips Macular involvement Macular hole At any stage, if present in the study eye Other causes of CNV Ocular histoplasmosis syndrome, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, pathologic myopia (spherical equivalent of negative 8 diopters or more or axial length of 25 mm or more), etc. *Including macular hemorrhage, scar, atrophy, fibrosis, and neovascularization
- 10.Individuals considered by the investigator to be ineligible for study participation for any reasons other than the inclusion and exclusion criteria
- 11.Employees of investigational sites, individuals directly involved with the conduct of the study, prisoners, and persons who are legally institutionalized
- 7.Individuals who have only one functional eye (monocular vision)
- 2.Individuals with any of the following concurrent diseases at screening or for a specified period of time: (1) Concurrent ocular disease Eye Criterion Study eye Significant ocular media opacity such as a cataract which, in the judgment of the investigator, interferes with retinal visualization or retinal imaging tests Aphakia or the absence of the posterior capsule [except for eyes with intraocular lens implant having undergone yttrium aluminum garnet (YAG) laser posterior capsulotomy] Vitreous hemorrhage within the past 4 weeks Uncontrolled ocular hypertension (defined as IOP ≥ 25 mmHg despite adequate treatment) Fellow eye Any diagnosis or signs of nAMD requiring treatment with an IVT anti-VEGF agent during the screening period or at study treatment initiation Either eye Scleromalacia Active or suspected periocular/ocular infection or ocular inflammation (e.g., keratitis, scleritis, etc.) within 4 weeks prior to the first dose of the IP (2) Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg (despite adequate treatment) (3) Uncontrolled diabetes mellitus, at the investigator’s discretion (4) Congestive heart failure with New York Heart Association (NYHA) functional classification 3 or 4 or any clinically significant heart disease including ventricular arrhythmia and atrial fibrillation, at the investigator’s discretion (5) Active systemic infection undergoing treatment or recurrent clinically significant infections within 4 weeks prior to the first dose of the IP
- 3.Individuals with any medical history of the following at screening: (1) Other ophthalmic disease in the study eye that may affect safety/efficacy assessments in the subject or may require medical/surgical interventions during the clinical study at the investigator’s discretion (e.g., vitreomacular traction, glaucoma undergoing treatment, retinal detachment, corneal dystrophy, etc.) (2) Diabetic retinopathy (DR)*, diabetic macular edema (DME), retinal vein occlusion (RVO), uveitis, or other vascular disease affecting the retina (other than nAMD) in either eye *Mild non-proliferative DR will be permitted. (3) Stroke, transient ischemic attack, pulmonary embolism, deep venous thrombosis, or myocardial infarction within the past 24 weeks (4) Hypersensitivity reactions to aflibercept or other drugs to be used in the clinical study (fluorescein, mydriatic drops, etc.) (5) Malignancy within the last 5 years (however, individuals with basal cell, cutaneous squamous cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma who are in stable long-term follow-up without therapeutic medication, procedures, or surgery can participate in this clinical trial) (6) Organ or bone marrow transplantation
- 4.Individuals with a history of any of the following medication or non-pharmacological treatment for the study eye: (1) Glaucoma filtering surgery, vitrectomy or corneal transplantation (2) Simple intraocular or periocular surgery (e.g., cataract surgery, simple neodymium yttrium aluminum garnet (Nd:YAG) laser capsulotomy on a pseudophakic eye due to posterior capsular opacification, etc.) within 12 weeks or eyelid surgery within 4 weeks prior to the screening visit [Laser iridotomy will be permitted.] (3) Macular photodynamic therapy (PDT) with verteporfin, transpupillary thermotherapy, radiotherapy, or retinal laser treatment (e.g., focal laser photocoagulation, pan-retinal photocoagulation, etc.) (4) Periocular radiotherapy (5) Any anti-vascular endothelial growth factor (anti-VEGF) treatment for nAMD (including participation in other clinical studies (6) Treatment for retinal detachment (medication or non-pharmacological treatment) (7) IVT corticosteroid injection, sub-tenon or periocular corticosteroid injection within 24 weeks or IVT corticosteroid implantation within 36 months prior to the screening visiti (8)Topical ocular corticosteroids administered for ≥ 30 consecutive days or for ≥ 60 non-consecutive days within 90 days prior to randomization
- 5.Individuals with any of the following medication or non-pharmacological treatment history: (1) Systemic anti-VEGF therapy within 12 weeks prior to the first dose of the IP (3) Any anti-VEGF treatment of nAMD in the fellow eye within 8 weeks prior to the first dose of the IP (including anti-VEGF) (Dietary supplements and vitamins will be permitted.) (4) Current use at screening of medications known to be toxic to the lens, retina, or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, vigabatrin, ethambutol. (5) Systemic corticosteroids administered within 12 weeks prior to the first dose of the IP (prednisolone ≤ 10 mg/day and equivalent dose administered for 14 days or less or inhaled/intranasal/dermal agents will be permitted.) (6) Other IP within 12 weeks or 5 times the half-life (whichever is longer) prior to the first dose of the IP
- 6.Individuals with BCVA of fewer than 34 letters measured by ETDRS letter score at the screening and baseline visits in the fellow eye
- 8.Pregnant [human chorionic gonadotropin (hCG) positive] or breastfeeding women of childbearing potential at the screening and baseline visits
- 9.Men or women of childbearing potential who are unwilling to use adequate methods of contraception* from the time of written informed consent to 12 weeks after the last dose of the IP * Hormonal contraceptives (oral contraceptive pill, contraceptive patch, etc.), intrauterine device or intrauterine system implantation, sterilization procedure or surgery (vasectomy, bilateral tubal ligation, etc.), complete abstinence
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 10 May 2024 | 102 |
 Croatia | Not Recruiting | 10 May 2024 | 28 |
 Poland | Not Recruiting | 10 May 2024 | 121 |
 Slovakia | Not Recruiting | 10 May 2024 | 38 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Eylea 40 mg/mL solution for injection in a vial | Comparator | SOLUTION FOR INJECTION | INTRAVITREAL USE | 2 | 48 | PRD3117103 |
FLUORESCEIN SODIUM | Other | — | INTRAVENOUS INJECTION | 500 | 3 | SUB13905MIG |