RBS-001 vs Eylea for Age-Related Macular Degeneration

Recruiting at 6 trial locations

Overseen By Matthew Gaver, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rophibio, Inc.

Must not be taking: Anti-VEGF, Corticosteroids, others

Disqualifiers: Hypertension, Diabetes, Heart disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

434 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical study is designed to demonstrate the equivalence of the two Investigational Products by comparing the efficacy, safety, tolerability and immunogenicity of RBS-001 and Eylea® in subjects with Neovascular age-related macular degeneration.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you are using medications known to be toxic to the eye or if you have used certain treatments like systemic anti-VEGF therapy or systemic corticosteroids recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Eylea for age-related macular degeneration?

Research shows that Eylea (aflibercept) can improve visual function and reduce central macular thickness in patients with age-related macular degeneration who did not respond to other treatments. Studies also report positive anatomical and functional outcomes in patients treated with Eylea for this condition. ^{1 2 3 4 5}

Is RBS-001 (Eylea) safe for humans?

Aflibercept (Eylea) has been shown to have a good safety profile in treating eye conditions like age-related macular degeneration, although there have been reports of sterile inflammation (swelling without infection) in some cases. ^{6 7 8 9 10}

How is the treatment RBS-001 different from other treatments for age-related macular degeneration?

RBS-001 is unique because it is being compared to Eylea®, a standard treatment for age-related macular degeneration, and may involve a novel approach or component not detailed in the available research. The studies mention epimacular brachytherapy (EMB), a treatment that uses targeted radiation, which could suggest a different mechanism of action compared to traditional drug therapies. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for individuals with Neovascular Age-Related Macular Degeneration. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and have the condition being studied.

Inclusion Criteria

I am 50 years old or older.

Individuals with BCVA of 34 to 73 letters measured by ETDRS letter score at the screening and baseline visits in the study eye

My eye condition involves fluid buildup confirmed by an OCT scan.

Exclusion Criteria

Individuals with any of the following concurrent diseases at screening or for a specified period of time: i. Concurrent ocular disease, ii. Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg (despite adequate treatment), iii. Uncontrolled diabetes mellitus, at the investigator's discretion, iv. 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, v. Active systemic infection undergoing treatment or recurrent clinically significant infections within 4 weeks prior to the first dose of the IP

Individuals with any medical history of the following at screening: i. 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.), ii. 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), iii. Stroke, transient ischemic attack, pulmonary embolism, deep venous thrombosis or myocardial infarction within the past 24 weeks, iv. Hypersensitivity reactions to aflibercept or other drugs to be used in the clinical study (fluorescein, mydriatic drops, etc.), v. 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), vi. Organ or bone marrow transplantation

Individuals with a history of any of the following medication or non-pharmacological treatment for the study eye: i. Glaucoma filtering surgery, vitrectomy or corneal transplantation, ii. 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), iii. Macular photodynamic therapy (PDT) with verteporfin, transpupillary thermotherapy, radiotherapy or retinal laser treatment (e.g., focal laser photocoagulation, pan-retinal photocoagulation, etc.), iv. Periocular radiotherapy, v. Any anti-VEGF treatment for nAMD (including participation in other clinical studies), vi. Treatment for retinal detachment (medication or non-pharmacological treatment), vii. IVT corticosteroid injection, sub-tenon or periocular corticosteroid injection within 24 weeks or IVT corticosteroid implantation within 36 months prior to the screening visit

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either RBS-001 or Eylea® for 48 weeks to compare efficacy, safety, tolerability, and immunogenicity

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Eylea®
• RBS-001

Trial Overview The study tests RBS-001 against Eylea®, both treatments for macular degeneration. It aims to compare their effectiveness, safety, tolerability, and potential to cause immune reactions in patients.

Participant Groups

Group I: RBS-001 treatment group Active Control 1 Intervention

All eligible subjects according to the inclusion/exclusion criteria will be randomized into the RBS-001 treatment group or Eylea® treatment group in a ratio of 1:1 with the BCVA score

Group II: Eylea® treatment group Active Control 1 Intervention

All eligible subjects according to the inclusion/exclusion criteria will be randomized into the RBS-001 treatment group or Eylea® treatment group in a ratio of 1:1 with the BCVA score

Who Is Running the Clinical Trial?

Rophibio, Inc.

Lead Sponsor

Trials

1

Recruited

430+

Findings from Research

In a study of 40 patients with neovascular age-related macular degeneration who switched from ranibizumab to aflibercept, contrast sensitivity improved significantly from baseline to week 12, indicating enhanced visual function.

The central retinal thickness decreased significantly, suggesting that aflibercept may effectively reduce fluid accumulation in the retina, which is crucial for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab. Nixon, DR., Flinn, NA.[2022]

In a study of 26 patients with neovascular age-related macular degeneration (nv-AMD), intravitreal injections of aflibercept (Eylea) led to a significant improvement in visual acuity over 14 months, with 61.5% of eyes showing improvement and a mean visual acuity change from 0.26 to 0.14 LogMAR (P=0.02).

The treatment also resulted in a significant reduction in central macular thickness from 409μm to 229μm (P<0.02), and no adverse events were reported, indicating that aflibercept is a safe and effective option for treating naïve patients with nv-AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. Papavasileiou, E., Zygoura, V., Richardson, T., et al.[2019]

A survey of 466 patients with wet age-related macular degeneration revealed that the most important factors influencing their treatment preferences were clarity of vision, treatment effects on symptoms, and quality of vision, highlighting the significance of visual outcomes in their care.

The study demonstrated that patients actively engage in their treatment management, as indicated by their high levels of knowledge and confidence, which can guide future clinical development to better align with patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Preferences in the Management of Wet Age-Related Macular Degeneration: A Conjoint Analysis. Skelly, A., Taylor, N., Fasser, C., et al.[2023]

In a study involving 30 patients with retinitis pigmentosa-associated cystoid macular oedema, intravitreal aflibercept (Eylea) was found to be safe, with no significant adverse events reported over 12 months.

While 37.9% of patients showed a reduction in central macular thickness (CMT) after treatment, there was no overall significant improvement in visual acuity, indicating that while some patients may benefit anatomically, this does not necessarily translate to better vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. Strong, SA., Peto, T., Bunce, C., et al.[2021]

Aflibercept, also known as Eylea, is a recombinant fusion protein that effectively binds to vascular endothelial growth factor (VEGF) family members, which are involved in abnormal blood vessel growth.

In November 2011, aflibercept received FDA approval for treating neovascular age-related macular degeneration, indicating its recognized efficacy and safety for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept. Stewart, MW., Grippon, S., Kirkpatrick, P.[2022]

Aflibercept (Eylea) is an effective anti-VEGF therapy for neovascular age-related macular degeneration (AMD), showing excellent safety and significant benefits in maintaining vision, as demonstrated in randomized trials.

Aflibercept, administered every 8 weeks after an initial loading dose, is clinically equivalent and statistically noninferior to ranibizumab (Lucentis), which is given every 4 weeks, indicating its potential as a more convenient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for neovascular age-related macular degeneration. Xu, D., Kaiser, PK.[2022]

In a study of 363 patients with chronic neovascular age-related macular degeneration, epimacular brachytherapy (EMB) did not reduce the number of anti-VEGF injections needed compared to ranibizumab monotherapy, indicating no added benefit in treatment frequency.

Over 36 months, patients receiving EMB experienced a significant decline in best-corrected visual acuity (BCVA) compared to those on ranibizumab alone, suggesting that EMB may be less effective in preserving vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. Jackson, TL., Soare, C., Petrarca, C., et al.[2023]

The Clinical Age-Related Maculopathy Staging (CARMS) system is a reliable and valid tool for classifying age-related maculopathy (ARM) in clinical settings, showing substantial agreement between clinical assessments and photographic evaluations in 492 eyes of 246 participants.

The CARMS system demonstrated high sensitivity (0.83) and specificity (0.97) for advanced age-related macular degeneration, making it effective for both clinical practice and research involving ARM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the clinical age-related maculopathy staging system. Seddon, JM., Sharma, S., Adelman, RA.[2022]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Switch to aflibercept in the treatment of neovascular age-related macular degeneration: 30-month results. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluating Efficacy of Aflibercept in Refractory Exudative Age-Related Macular Degeneration With OCT Segmentation Volumetric Analysis. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Patient Preferences in the Management of Wet Age-Related Macular Degeneration: A Conjoint Analysis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Aflibercept. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Aflibercept-Related Sterile Intraocular Inflammation Outcomes. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for neovascular age-related macular degeneration. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Macular epiretinal brachytherapy in treated age-related macular degeneration: MERITAGE study: twelve-month safety and efficacy results. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT): A Phase 3 Randomized Controlled Trial. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the clinical age-related maculopathy staging system. [2022]

15. Germany pubmed.ncbi.nlm.nih.gov

Two-year outcomes of episcleral brachytherapy adjunct to anti-VEGF therapy for treatment-resistant nAMD. [2022]