Efficacy and Safety Evaluation of Intravitreal EYE103 Versus Ranibizumab in Diabetic Macular Edema: A Randomized, Double-Masked, Phase 2/3 Study
- Trial ID
- 2025-520809-12-00
- Protocol
- EYE-RES-103
- Sponsor
- Eyebiotech Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate that **EYE103** (0.5 mg or 0.8 mg) is non-inferior to **ranibizumab** 0.5 mg in terms of efficacy, as measured by the mean change in Best Corrected Visual Acuity (BCVA) up to and including Week 52. This change will be assessed using the standardized ETDRS chart from Day 1 to Year 1, specifically averaging the results from Weeks 48 and 52. The clinical relevance of this objective lies in its potential to establish **EYE103** as an effective alternative treatment for patients with **Diabetic Macular Edema**, potentially offering similar visual acuity improvements as the current standard treatment with **ranibizumab**.
Participants
The clinical trial involves a total of **495 participants** diagnosed with **Diabetic Macular Edema**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their ability to understand the study procedures and provide informed consent. The trial does not include a vulnerable population. Key lifestyle considerations include the requirement for female participants of childbearing potential to have a negative pregnancy test and use highly effective contraception methods during the study and for a specified period after the last dose. Male participants must be surgically sterile or agree to use contraception and refrain from donating sperm during and after the study period. The trial population was chosen to ensure a comprehensive evaluation of the investigational drug's efficacy compared to ranibizumab, with no specific emphasis on dietary or physical activity habits.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-masked, multi-center, three-arm pivotal Phase II/III study. The primary objective is to evaluate the efficacy and safety of intravitreal EYE103 compared with intravitreal **ranibizumab** (0.5 mg) in participants with **Diabetic Macular Edema**. The trial aims to demonstrate that EYE103 (0.5 mg or 0.8 mg) is non-inferior to ranibizumab 0.5 mg, as measured by the mean change in Best Corrected Visual Acuity (BCVA) up to and including Week 52. This change will be assessed using the standardized ETDRS chart from Day 1 to Year 1 (average of Weeks 48 and 52).
The trial is expected to commence recruitment on May 1, 2025, and conclude by June 30, 2028. Participants will be involved in the study for a maximum treatment period of 24 months. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and administer the study drug, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be male or female aged 18 years or older, with females of childbearing potential required to have a negative pregnancy test and agree to use effective contraception. Males must be surgically sterile or agree to use contraception.
Participants may be withdrawn from the study if they experience adverse events that compromise safety, fail to comply with study procedures, or withdraw consent. The primary endpoint is the mean change in ETDRS BCVA from Baseline (Day 1) to Year 1. The study will utilize a solution for injection administered via intravitreal use. The investigational product, EYE103, is compared against ranibizumab, with both products being solutions for injection. The trial is not classified as a low-intervention study, and it is not designated as an orphan drug trial.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and comparator medications. The **experimental medication** EYE103 is a solution for injection, developed by EYEBIOTECH LIMITED. It is administered via intravitreal use, with two dosing regimens being evaluated: 0.5 mg and 0.8 mg. The maximum total dose for the 0.5 mg regimen is 12 mg, while for the 0.8 mg regimen, it is 19.2 mg. The treatment period for both regimens extends up to 24 weeks. EYE103 is a protein-based substance, and its administration is monitored to ensure compliance with the dosing schedule.
The **comparator treatment** in this study is Lucentis, a 10 mg/ml solution for injection containing the active substance **ranibizumab**. Manufactured by NOVARTIS EUROPHARM LIMITED, Lucentis is also administered via intravitreal use. The dosage for ranibizumab is 0.5 mg per administration, with a maximum total dose of 12 mg over a 24-week treatment period. As a protein-based therapeutic, ranibizumab is used to evaluate the efficacy and safety of EYE103 in comparison to an established treatment for diabetic macular edema.
Additionally, the study utilizes Fluorescein Alcon® 10% Injektionslösung as an **auxiliary treatment**. This solution for injection, containing **fluorescein sodium**, is used as a contrast agent. It is administered as needed, with a maximum daily dose of 500 mg and a total dose not exceeding 3 g over a 6-week period. The administration of fluorescein sodium is conducted via injection, and its use is primarily for diagnostic purposes within the study framework.
Efficacy
The efficacy of the investigational product EYE103 will be assessed in a randomized, double-masked, multi-center, 3-arm pivotal Phase 2/3 clinical trial. The primary objective is to demonstrate that EYE103, administered at doses of 0.5 mg or 0.8 mg, is non-inferior to **ranibizumab** 0.5 mg in participants with Diabetic Macular Edema. Efficacy will be evaluated by measuring the mean change in Best Corrected Visual Acuity (BCVA) using the standardized Early Treatment Diabetic Retinopathy Study (ETDRS) chart. This change will be assessed from Baseline (Day 1) to Year 1, specifically averaging the results from Weeks 48 and 52.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity
- Be male or female ≥18 years of age.
- If female, have a negative serum pregnancy test at screening and further negative urine tests immediately before each dose of study medication if the participant is a female of childbearing potential (including those with <2 years since the onset of menopause, amenorrhea for <1 year, or not surgically sterile); such participants must agree to use a highly effective method of contraception from screening up to and including 3 months after the last dose of study drug (see Appendix B). She must also agree not to donate oocytes from screening up to and including 3 months after the last dose of study drug.
- If male, be surgically sterile for at least 12 weeks, or agree to use an acceptable method of contraception, such as a condom, and a second highly effective method of contraception (see Appendix F) from Screening up to and including 90 days after the last dose of study drug (see Appendix B). He must also agree not to donate sperm from the time of the first dose until 12 weeks after the last dose of study drug.
Exclusion Criteria
- Be pregnant or breastfeeding.
- Have history of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of screening.
- Have any treatment for complications of cataract surgery with steroids or yttrium-aluminum garnet (YAG) laser capsulotomy within 90 days of Screening.
- Have had pan-retinal photocoagulation or focal/grid thermal laser photocoagulation in the study eye within 90 days of screening.
- Have any history of retinal detachment or treatment or surgery for retinal detachment in the study eye.
- Have any history of uveitis in either eye.
- Have significant media opacities, including cataract, in the study eye that might interfere with VA, assessment of safety, OCT, or fundus photography in the opinion of the reading center.
- Have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
- Have a cataract in the study eye that, in the judgment of the investigator is expected to require surgical extraction within 4 months of screening.
- Have aphakia in the study eye.
- Have an allergy to fluorescein dye.
- Have had vitrectomy in the study eye.
- Have active retinal disease other than the condition (DME/diabetic retinopathy) under investigation in the study eye.
- Have active or suspected ocular or periocular infection or inflammation in either eye at day 1.
- Currently have evidence of, or a history of any clinically significant autoimmune, cardiovascular, hematologic, hepatic, metabolic, peripheral vascular, renal, or respiratory disease, which, in the opinion of the investigator, would prevent the participant from completing the required assessments for this study.
- Have a known hypersensitivity to any of the components of EYE103 formulation or prior hypersensitivity to mAbs.
- Have had renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis or have renal failure anticipated to require hemodialysis or peritoneal dialysis at any time during the study.
- Have previously participated in any study of EYE103.
- Have uncontrolled blood pressure, defined as systolic ≥180 mmHg and/or diastolic ≥100 mmHg while a participant is at rest If a participant’s initial reading exceeds these values, a second reading may be obtained later the same day or on another day during the screening period. If the participant’s blood pressure is controlled by antihypertensive medication, the participant should be taking the same medication continuously for at least 30 days prior to Day 1.
- Have history of stroke (cerebral vascular accident) or myocardial infarction within 180 days prior to Day 1.
- Have any active malignancy.
- Have any history of organ transplant.
- If treatment-experienced for DME have a history of any of the following treatments within the noted time windows: • Have had prior treatment with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO) within 120 days prior to the Screening visit in the study eye • Have had an IVT with other anti-VEGF treatments (ranibizumab, bevacizumab, aflibercept [2 mg], brolucizumab, pegaptanib sodium) in the study eye within 90 days of the Screening visit • Had prior IVT investigational agents in either eye at any time • Had treatment with ocriplasmin (JETREA®) in the study eye at any time • Had previous use of ILUVIEN® at any time, of OZURDEX® IVT implants within 180 days of the Screening visit, or any other intraocular or periocular corticosteroids in the study eye within 90 days of the Screening visit
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 01 May 2025 | 20 |
 Croatia | Not Recruiting | 01 May 2025 | 10 |
 Czechia | Not Recruiting | 01 May 2025 | 70 |
 France | Not Recruiting | 01 May 2025 | 50 |
 Germany | Not Recruiting | 01 May 2025 | 30 |
 Hungary | Not Recruiting | 01 May 2025 | 60 |
 Italy | Not Recruiting | 01 May 2025 | 35 |
 Latvia | Not Recruiting | 01 May 2025 | 20 |
 Poland | Not Recruiting | 01 May 2025 | 70 |
 Portugal | Not Recruiting | 01 May 2025 | 25 |
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 |
|---|---|---|---|---|---|---|
Lucentis 10 mg/ml solution for injection | Comparator | SOLUTION FOR INJECTION | INTRAVITREAL USE | 0.5 | 24 | PRD2393543 |
EYE103 | Test | SOLUTION FOR INJECTION | INTRAVITREAL USE | 0.8 | 24 | PRD11652369 |
Fluorescein Alcon® 10 % Injektionslösung | Other | INJEKTIONSLÖSUNG | SOLUTION FOR INJECTION | 500 | 6 | PRD7457188 |
EYE103 | Test | SOLUTION FOR INJECTION | INTRAVITREAL USE | 0.5 | 24 | PRD10413977 |