EYE103 for Diabetic Macular Edema

(BAROLO Trial)

Recruiting at 151 trial locations

Overseen By Charles Miller, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: EyeBiotech Ltd.

Must not be taking: Retinal toxicity drugs

Disqualifiers: Pregnancy, Recent eye surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

960 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, EYE103, to determine its effectiveness for people with blurry vision caused by diabetic macular edema (DME), a condition where fluid accumulates in the eye due to diabetes. Participants will receive one of two doses of EYE103 or an existing treatment, ranibizumab (an injection for eye conditions), to compare their effects. The study aims to identify which treatment is most effective and safest for improving vision. People with type 1 or type 2 diabetes who have vision problems primarily due to DME might be suitable candidates for this trial.

As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in eye care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using drugs with known retinal toxicity or have had certain eye treatments recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that EYE103 appears safe for treating diabetic macular edema (DME). One study found that EYE103 improved vision and was generally well-tolerated, with most participants experiencing no serious side effects. Some individuals might experience mild reactions, such as eye irritation, but current data suggests the treatment is safe.

Ranibizumab, the other treatment in this study, has already received approval for DME and is known for its safety, having been widely used with few safety concerns. Researchers are carefully comparing both treatments to determine which is safer and more effective for people with DME. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about EYE103 for diabetic macular edema because it offers a potential new approach to treatment with its unique mechanism of action. Most current treatments, like Ranibizumab, target and inhibit VEGF (vascular endothelial growth factor) to reduce fluid leakage and swelling in the eye. EYE103, however, brings a fresh angle by potentially working through a different biological pathway, which could offer enhanced efficacy or benefits for patients who do not respond optimally to existing therapies. Additionally, EYE103 is being tested in both low and high dose forms, providing flexibility in tailoring treatment to patient needs. This new approach could lead to improved outcomes and more personalized care for individuals with this condition.

What evidence suggests that this trial's treatments could be effective for diabetic macular edema?

Research shows that EYE103, also known as Restoret, could be a helpful treatment for diabetic macular edema (DME). Participants in this trial will receive either a low or high dose of EYE103. Earlier studies showed that EYE103 improved vision clarity and reduced eye swelling in patients with DME. These findings suggest that EYE103 helps manage the condition by addressing key symptoms. Additionally, the treatment was well-tolerated, with patients not experiencing major side effects. While more information is needed to confirm these benefits, the initial results are promising. ^{2 6 7 8 9}

Who Is on the Research Team?

Charles Miller, MD PhD

Principal Investigator

EyeBiotech Ltd.

Are You a Good Fit for This Trial?

This trial is for individuals with diabetic macular edema (DME), a condition affecting the eye. Participants should have DME in at least one eye and be willing to receive treatments every 4 weeks for the first year, with adjustments thereafter based on an individualized plan.

Inclusion Criteria

Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity

I have diabetes with an HbA1c of 12% or less.

My vision loss is mainly due to diabetic macular edema.

Exclusion Criteria

Be pregnant or breastfeeding

I have had specific treatments for diabetic eye disease within certain time frames.

I had cataract or glaucoma surgery in one eye within the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Year 1

Participants receive intravitreal injections of EYE103 or ranibizumab every 4 weeks

52 weeks

12 visits (in-person)

Treatment Year 2

Participants continue treatment with a personalized treatment interval algorithm

52 weeks

Visits every 4 weeks, adjusted per algorithm

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EYE103
• Ranibizumab

Trial Overview The study compares two doses of a medication called EYE103 against Ranibizumab, which is already used for DME. Patients will be randomly assigned to one of three groups and treated regularly, with treatment frequency adjusted in the second year.

How Is the Trial Designed?

Group I: EYE103 Low Dose Treatment Arm Experimental Treatment 1 Intervention

EYE103 Low Dose Treatment Arm

Group II: EYE103 High Dose Treatment Arm Experimental Treatment 1 Intervention

EYE103 High Dose Treatment Arm

Group III: Ranibizumab Treatment Arm Active Control 1 Intervention

Ranibizumab Treatment Arm

Who Is Running the Clinical Trial?

EyeBiotech Ltd.

Lead Sponsor

Trials

3

Recruited

1,100+

Published Research Related to This Trial

A patient treated with ranibizumab for diabetic macular edema experienced severe ocular complications, including anterior ischemic optic neuropathy (AION) and central retinal artery occlusion (CRAO), after multiple injections over 12 months.

Despite initial improvements in visual acuity and retinal thickness, the patient suffered significant vision loss and vascular complications, highlighting the need for careful monitoring of patients receiving intraocular anti-VEGF treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential anterior ischemic optic neuropathy and central retinal artery and vein occlusion after ranibizumab for diabetic macular edema. Battaglia Parodi, M., Iacono, P., Cascavilla, ML., et al.[2019]

In a 36-month study involving 290 patients with diabetic macular edema (DME), ranibizumab 0.5 mg demonstrated a mean improvement of 7.4 letters in best-corrected visual acuity (BCVA) after 12 months, indicating its effectiveness in treating visual impairment.

The study found that patients received an average of 5.1 injections over 10.4 visits, which is fewer than what is typically reported in clinical trials, while no new safety concerns were identified, supporting the treatment's safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema: 12-Month Results from the 36-Month BOREAL-DME Study. Massin, P., Creuzot-Garcher, C., Kodjikian, L., et al.[2019]

In a study involving 5,781 patients over 24 months, intravitreal ranibizumab injections for treating eye conditions showed that 79.7% of patients reported no adverse events (AEs), indicating a generally favorable safety profile.

While 2,687 AEs were reported, with 30.3% classified as serious, the overall rate of AEs decreased over time, and no new safety concerns were identified, suggesting that ranibizumab is a safe option for patients under real-world conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial. Ziemssen, F., Hammer, T., Grueb, M., et al.[2022]

In a pooled analysis of safety data from 5 clinical trials involving 4,347 patients with neovascular age-related macular degeneration (nAMD), it was found that patients aged 85 years and older had a higher incidence of systemic serious adverse events (SAEs) compared to those younger than 85, indicating that age is a significant risk factor.

Despite the increased risk of SAEs in older patients, the use of ranibizumab did not significantly elevate the risk of most systemic SAEs, suggesting that the treatment is generally safe for elderly patients, although the analysis was limited by the small number of events for certain outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Systemic Safety of Ranibizumab in Patients 85 Years and Older with Neovascular Age-Related Macular Degeneration. Dugel, PU., Singh, N., Francom, S., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06957080

NCT06957080 | A Study of 2 Doses of EYE103 Compared ... EYE-RES-103 is a randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ...

2. merck.com merck.com/news/merck-and-eyebio-announce-initiation-of-phase-2b-3-clinical-trial-for-restoret-for-the-treatment-of-diabetic-macular-edema/

Merck and EyeBio Announce Initiation of Phase 2b/3 ... Diabetic macular edema (DME) is a serious retinal condition that poses a risk to vision, potentially leading to blindness and a reduced quality ...

3. ophthalmologytimes.com ophthalmologytimes.com/view/eyebio-announces-positive-data-from-first-in-human-ph1b-2a-amarone-trial-of-restoret-for-dme-dvamd

EyeBio announces positive data from first-in-human Ph1b ... Twelve-week data from the Ph1b/2a AMARONE trial reveals Restoret to be well-tolerated in patients with diabetic macular edema and neovascular age-related ...

4. tnretina.com tnretina.com/research/non-enrolling-studies

Ongoing Clinical Trials EYE103-101 is a 2-part study assessing safety and preliminary efficacy of EYE103 in patients with diabetic macular edema (DME) given as monotherapy or ...

5. hcplive.com hcplive.com/view/charles-c-wykoff-md-phd-phase-1b-2a-results-on-restoret-for-dme-namd

Phase 1b/2a Results on Restoret for DME, nAMD In the AMARONE trial, Restoret showed safety and efficacy, improving visual acuity and reducing central subfield thickness in DME patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05919693

NCT05919693 | A 2-part Study Consisting of Multiple ... EYE103-101 is a 2-part study assessing safety and preliminary efficacy of EYE103 in patients with diabetic macular edema (DME) given as monotherapy or ...

7. ophthalmologytimes.com ophthalmologytimes.com/view/charles-miller-md-phd-on-dme-research-and-the-initiation-of-the-phase-2b-3-brunello-trial

Charles Miller, MD, PhD, on DME research and the ... ... EYE103 for the treatment of patients with diabetic macular edema (DME). ... EyeBio Announces Positive Visual, Anatomic and Safety Data from ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06957080

NCT06957080 | A Study of 2 Doses of EYE103 Compared ... EYE-RES-103 is a randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ...

9. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-eye103-compared-to-ranibizumab-for-patients-with-diabetic-macular-edema/

Study on the Effectiveness and Safety of EYE103 ... The purpose of the study is to evaluate whether EYE103 is as effective as ranibizumab in improving vision in people with Diabetic Macular Edema.