EYE103 for Diabetic Macular Edema

(BRUNELLO Trial)

Not currently recruiting at 174 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, Cataract 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: 17

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EYE103 for diabetic macular edema (DME), a condition that causes vision problems due to diabetes. The study aims to compare the effectiveness of two different doses of EYE103 with an existing treatment, ranibizumab, an injection used for eye conditions. Participants will receive treatments every four weeks for the first year, after which the schedule will adjust based on their needs. Individuals with type 1 or type 2 diabetes who experience vision loss due to DME might be suitable for this trial. As a Phase 2, Phase 3 trial, this study is crucial for evaluating the effectiveness of EYE103 and represents the final step before FDA approval, offering participants a chance to contribute to advancing treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop using drugs with known retinal toxicity, such as Hydroxychloroquine, pentosan polysulfate sodium, and amiodarone. If you have been treated for diabetic macular edema with certain medications recently, you may also need to stop those before joining the trial.

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

Research has shown that EYE103 is well-tolerated in early studies. In one study, patients with diabetic macular edema experienced promising safety results after 12 weeks of using EYE103, with no serious side effects reported. This early safety information suggests EYE103 is safe for humans. As the current trial continues, more data will help confirm these findings. ^{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 might offer a new way to manage this condition. Unlike the standard treatment, Ranibizumab, which primarily focuses on inhibiting vascular endothelial growth factor (VEGF), EYE103 may have a different mechanism of action that offers additional benefits. The trial is exploring both low and high doses of EYE103, which could provide insights into its effectiveness and potential advantages over existing treatments. This could mean more personalized and effective treatment options for patients struggling with diabetic macular edema.

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

Research has shown that EYE103, a new treatment for diabetic macular edema, appears promising in early studies. Initial results suggest that EYE103 improves vision and is well-tolerated by patients. This trial includes separate arms for both low and high doses of EYE103 to evaluate its effectiveness. In contrast, ranibizumab, compared in a separate treatment arm, is already known to improve vision for similar eye conditions. Both treatments are being carefully studied in this trial to understand their potential in managing diabetic macular edema. ^{1 3 4 6 7}

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 causing swelling in the retina due to diabetes. Participants should have this specific eye condition and be willing to receive treatments every 4 weeks for at least one year, with possible adjustments thereafter.

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

I have had specific treatments for diabetic macular edema within certain time frames.

Be pregnant or breastfeeding

I have not had steroid treatment or YAG laser for cataract surgery issues in the last 90 days.

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

13 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 new medication called EYE103 against an established treatment, Ranibizumab, for DME. It's randomized and double-masked, meaning neither participants nor researchers know who gets which treatment. The goal is to determine the effectiveness and safety of EYE103.

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

Intravitreal injections of ranibizumab (Lucentis) have been shown to be an effective and safe treatment option for macular edema caused by retinal vein occlusion, which is a major cause of vision impairment.

Compared to traditional treatments like laser photocoagulation or intravitreal triamcinolone, ranibizumab offers significant improvements in managing this condition, as supported by data from randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ranibizumab in Macular Edema following Retinal Vein Occlusion. Gallego-Pinazo, R., Dolz-Marco, R., Marín-Lambíes, C., et al.[2021]

The RELIGHT clinical trial demonstrated that ranibizumab treatment for diabetic macular oedema led to significant improvements in visual functioning as measured by the NEI-VFQ over 18 months, indicating its efficacy in enhancing patients' quality of life.

Despite improvements in patient satisfaction reported by the MacTSQ, there was no correlation between visual acuity and satisfaction scores, suggesting that factors influencing patient satisfaction may not be fully captured by traditional measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in the RELIGHT clinical trial of ranibizumab in diabetic macular oedema. Chakravarthy, U., Pearce, I., Banerjee, S., et al.[2022]

In a 12-month study involving patients with clinically significant diabetic macular edema, both 0.5 mg and 1.0 mg doses of ranibizumab led to significant reductions in central foveal thickness and improvements in visual acuity, with the 1.0 mg dose showing a greater average improvement of +7.9 letters compared to +3.8 letters for the 0.5 mg dose.

The study demonstrated that ranibizumab is effective in treating diabetic macular edema, with both doses resulting in positive outcomes, although the higher dose provided a more substantial improvement in visual acuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Ranibizumab 0.5 mg Versus 1.0 mg for the Treatment of Patients With Clinically Significant Diabetic Macular Edema: A Randomized, Clinical Trial. Ferrone, PJ., Jonisch, J.[2017]

In two phase 3 clinical trials involving 759 patients, treatment with intravitreal ranibizumab significantly improved patient-reported vision-related function, as measured by the NEI VFQ-25 scores, compared to sham treatment at both 12 and 24 months.

The improvement in vision-related function was particularly notable in better-seeing eyes, with a mean score increase of 10.9 points at 24 months for patients receiving 0.3 mg ranibizumab in the RIDE trial, indicating its efficacy in enhancing quality of life for those with diabetic macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE. Bressler, NM., Varma, R., Suñer, IJ., et al.[2022]

In a study of 30 eyes with persistent diabetic macular edema (DME) after treatment with bevacizumab, 0.3 mg ranibizumab improved visual acuity by an average of +6.5 letters over one year, indicating its efficacy as a treatment option.

Ranibizumab also led to a significant reduction in central subfield thickness, with an overall mean decrease of 116 µm, suggesting improved anatomical outcomes in patients with DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranibizumab 0.3 mg for Persistent Diabetic Macular Edema After Recent, Frequent, and Chronic Bevacizumab: The ROTATE Trial. Fechter, C., Frazier, H., Marcus, WB., et al.[2022]

Ranibizumab (Lucentis®) significantly improves visual acuity in patients with macular oedema following retinal vein occlusion, as shown in two phase III trials with monthly injections leading to better outcomes than sham injections at 6 months.

The treatment was generally well tolerated, with adverse events aligning with those seen in other conditions treated with ranibizumab, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranibizumab: in macular oedema following retinal vein occlusion. Garnock-Jones, KP.[2021]

Ranibizumab treatment significantly improved diabetic retinopathy (DR) outcomes, especially in patients with moderately severe to severe nonproliferative DR, showing a 78.4% to 81.1% rate of 2-step or more improvement at 24 months compared to only 11.6% in the sham group.

Patients receiving ranibizumab had a threefold reduction in the probability of experiencing new proliferative events by month 36, indicating its efficacy in preventing disease progression in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranibizumab Induces Regression of Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy. Wykoff, CC., Eichenbaum, DA., Roth, DB., et al.[2019]

In a study of 100 patients with diabetic macular oedema, combination treatment with ranibizumab and macular LASER showed better visual and retinal thickness outcomes compared to LASER monotherapy over a two-year follow-up period.

The need for ranibizumab injections decreased significantly from an average of 3.86 in the first year to 2.02 in the second year, indicating that the treatment becomes more effective over time without serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment of diabetic macular oedema: a comparison of combined ranibizumab plus macular LASER with macular LASER monotherapy. Zygoura, V., Papavasileiou, E., Vavvas, DG., et al.[2019]

In a 36-week crossover study involving 56 participants with diabetic macular edema, ranibizumab showed a statistically significant improvement in visual acuity (6.6 letters) compared to bevacizumab (5.3 letters), indicating ranibizumab may be slightly more effective for this condition.

Ranibizumab also resulted in a greater reduction in central retinal thickness (-137 μm) compared to bevacizumab (-89 μm), suggesting it may provide better structural benefits in addition to visual improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema. Wiley, HE., Thompson, DJ., Bailey, C., et al.[2022]

Intravitreal injections of ranibizumab significantly improved visual acuity and reduced central retinal thickness in patients with macular edema due to retinal vein occlusion, with average improvements of 9 letters in visual acuity and a decrease of 195 μm in retinal thickness after each injection.

The treatment was found to be safe, with no local or systemic adverse effects reported, but further long-term studies are needed to compare its efficacy against the natural progression of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal ranibizumab for macular oedema secondary to retinal vein occlusion: a retrospective study of 34 eyes. Puche, N., Glacet, A., Mimoun, G., et al.[2015]

Citations

1. 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 ... The dual primary endpoints are safety and mean change in best-corrected visual acuity (BCVA) from baseline to week 52 in the study eye of the ...

2. 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 ...

3. 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, ...

4. modernretina.com modernretina.com/view/merck-and-eyebio-announce-initiation-of-phase-2b-3-brunello-trial-evaluating-mk-3000-for-dme

Merck and EyeBio announce initiation of phase 2b/3 ... MK-3000, formally known as EYE103, is an investigational, potentially first-in-class tetravalent, tri-specific antibody that acts as an ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24491642/

the RESTORE extension study Conclusions: Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06571045

NCT06571045 | A Study to Evaluate the Efficacy and ... A randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ranibizumab.

7. vistacenter.org vistacenter.org/resource/early-safety-efficacy-results-positive-for-restoret-in-dme/

Early safety, efficacy results positive for Restoret in DME Restoret showed promising safety and efficacy results at 12 weeks in 26 patients with treatment-naive DME, according to a press release from EyeBio. “Restoret ...