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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, RBS-001 (an experimental treatment) and Eylea®, for individuals with neovascular age-related macular degeneration, a serious eye condition that can cause vision loss. The researchers aim to determine if RBS-001 matches Eylea® in effectiveness, safety, and side effects. Those diagnosed with this condition and experiencing symptoms like fluid buildup or specific retinal changes might qualify for the study. Participants will receive either RBS-001 or Eylea® through random assignment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Research shows that Eylea®, also known as aflibercept, is safe for treating eye conditions like age-related macular degeneration. In previous studies, patients using Eylea® generally tolerated it well, with few serious side effects.

For RBS-001, which is similar to Eylea®, early studies suggest it is also well-tolerated. These studies indicate that RBS-001, based on aflibercept, has a similar safety profile to Eylea®. Most patients experience only mild side effects, if any.

Overall, both treatments have been tested in many patients, and serious side effects are rare. Those considering joining a trial can find reassurance in this safety information based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

RBS-001 is unique because it could offer a new approach to treating age-related macular degeneration (AMD). Unlike other treatments that primarily focus on inhibiting VEGF, like Eylea®, RBS-001 might target different pathways involved in the progression of AMD, potentially offering improved outcomes or benefits for patients. Researchers are excited about RBS-001 because it has the potential to enhance vision preservation and could lead to fewer injections, making it more convenient for patients. If successful, RBS-001 could represent a significant advancement in the fight against AMD, offering new hope for those affected by this vision-threatening condition.

What evidence suggests that this trial's treatments could be effective for age-related macular degeneration?

This trial will compare RBS-001 with Eylea for treating age-related macular degeneration. Research has shown that Eylea (aflibercept) improves vision and reduces swelling in the central part of the retina for people with neovascular age-related macular degeneration (nAMD). Eylea blocks a protein that causes the growth of abnormal blood vessels in the eye, the main issue in nAMD. Patients using treatments similar to RBS-001, also based on aflibercept, have shown promising results in managing this condition. In real-world use, a similar treatment called brolucizumab effectively reduced fluid in the retina for nAMD patients. This suggests that RBS-001 could potentially be as effective as Eylea in treating this eye condition. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.eu clinicaltrials.eu/trial/study-comparing-rbs-001-and-aflibercept-for-patients-with-neovascular-age-related-macular-degeneration/

Study Comparing RBS-001 and Aflibercept for Patients ... This study investigates the effectiveness and safety of RBS-001, an aflibercept-based treatment, compared to Eylea in patients with neovascular age-related ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12167219/

Real-World Outcomes of Brolucizumab Treatment in ... In a real-world clinical setting, brolucizumab was effective at drying the retina in treatment-naïve and pre-treated Japanese nAMD patients.

3. withpower.com withpower.com/trial/phase-3-neovascular-age-related-macular-degeneration-namd-8-2024-b19b0

RBS-001 vs 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04423718

NCT04423718 | Study of the Effects of High Dose ... In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5667400/

Effects of Aflibercept for Neovascular Age-Related Macular ... Twelve-month outcomes of ranibizumab vs. aflibercept for neovascular age-related macular degeneration: data from an observational study. Ophthalmology. 2016 ...

6. ctv.veeva.com ctv.veeva.com/study/a-phase-3-clinical-trial-to-compare-rbs-001-to-eylea-r-in-subjects-with-neovascular-age-related-macul

A Phase 3 Clinical Trial to Compare RBS-001 to Eylea® in ... This is a phase 3 clinical trial to compare efficacy, safety, tolerability and immunogenicity of RBS-001 to Eylea® in subjects with neovascular ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07158775

NCT07158775 | A Phase 1/2 Study to Evaluate the Safety ... This is a seamless Phase 1/2 study in up to 10 patients for Phase 1 and 30 patients Phase 2 in patients with GA secondary to dry AMD. Official ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11039576/

Real-World Safety Outcomes with Brolucizumab in ... In this large real-world brolucizumab safety study, 3.4% of eyes experienced an IOI, RV, and/or RO event.