Faricimab or Fluocinolone Acetonide for Vision Loss

(AL Trial)

Recruiting at 21 trial locations

Overseen By Cynthia Stockdale, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jaeb Center for Health Research

Disqualifiers: Opaque media, Prior vitrectomy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, faricimab and fluocinolone acetonide, for individuals experiencing vision loss after treating choroidal melanoma with a radioactive implant. The researchers aim to determine if either treatment can improve or stabilize vision more effectively than monitoring the condition without intervention. Participants will receive either an injection of faricimab (a new potential drug), an implant of fluocinolone acetonide (a corticosteroid), or be placed in an observation group. Suitable candidates have had a radioactive implant for eye cancer and do not have other causes of vision loss. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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

Earlier studies found faricimab to be as safe as aflibercept, a well-known eye treatment. Few cases of swelling inside the eye occurred, indicating good patient tolerance.

Real-world studies have shown that fluocinolone acetonide is safe for long-term use in treating eye conditions. It has improved vision in patients with diabetic macular edema, demonstrating a good safety record in other eye treatments.

Both treatments have undergone human testing and are considered safe and well-tolerated based on past studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for vision loss because they offer promising alternatives to current options. Faricimab is unique because it targets two pathways involved in retinal diseases—angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A)—potentially providing more comprehensive protection against vision loss. Unlike standard anti-VEGF treatments that focus only on VEGF, faricimab's dual-action mechanism might offer enhanced effectiveness. Meanwhile, fluocinolone acetonide stands out with its long-lasting intravitreal implant that slowly releases medication over time, which could reduce the frequency of injections needed compared to typical corticosteroid treatments. Both treatments aim to improve patient outcomes and convenience, which is why they're generating excitement in the medical community.

What evidence suggests that this trial's treatments could be effective for vision loss?

In this trial, participants will receive either faricimab or fluocinolone acetonide intravitreal implants. Previous studies have shown that faricimab holds promise for treating eye conditions like diabetic macular edema and age-related macular degeneration by improving vision and reducing retinal damage. Faricimab targets two specific processes that cause blood vessels in the eye to grow and leak, helping to maintain better vision over time. Research on fluocinolone acetonide intravitreal implants indicates significant vision improvement. Specifically, one study found that about one-third of patients experienced vision improvement by three lines or more on an eye chart. Both treatments have effectively managed eye conditions and show potential for improving vision after treatment for choroidal melanoma. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with primary uveal melanoma treated with plaque brachytherapy, who have a baseline vision of at least 20/200 Snellen equivalent and no other causes for visual loss. The tumor must not be under the center of the fovea or touching the optic disc edge, and the macula should receive a dose of ≥30 Gy.

Inclusion Criteria

My eye tumor is not located under the central part of my vision.

Your vision is at least 20/200 or better on the eye chart.

Important requirements for participating in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravitreal faricimab injections or fluocinolone acetonide intravitreal implants

3 years

Regular visits for injections or implants

Observation

Participants are monitored for the development of macular edema and visual acuity changes

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Faricimab
• fluocinolone acetonide

Trial Overview The study compares two treatments to prevent vision loss from radiation retinopathy after choroidal melanoma treatment: injections of Faricimab into the eye (intravitreal) versus Fluocinolone Acetonide implants in the eye, against just watching without treatment.

How Is the Trial Designed?

Group I: Intravitreal faricimab Active Control 1 Intervention

Study eyes assigned to receive faricimab will receive a dose of 6.0 mg of faricimab. Faricimab is supplied in a single use vial.

Group II: Fluocinolone Acetonide Intravitreal Implants Active Control 1 Intervention

Study eyes assigned to receive fluocinolone acetonide intravitreal implant will receive a dose of 0.19 mg fluocinolone acetonide intravitreal implant (Iluvien). The implant is supplied in a sterile single use applicator with a 25-gauge needle

Group III: Observation Active Control 1 Intervention

Faricimab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vabysmo for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular edema (DME)
• Macular edema following retinal vein occlusion (RVO)

Approved in European Union as Vabysmo for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular edema (DME)

Approved in Canada as Vabysmo for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular edema (DME)

Who Is Running the Clinical Trial?

Jaeb Center for Health Research

Lead Sponsor

Trials

162

Recruited

36,200+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Alimera Sciences

Industry Sponsor

Trials

14

Recruited

3,000+

Published Research Related to This Trial

In a study of 23 eyes with chronic diabetic macular edema (DME), the intravitreal fluocinolone acetonide implant showed modest improvements in visual acuity and central macular thickness over 12 months, particularly in non-vitrectomized eyes.

The treatment was effective in both vitrectomized and non-vitrectomized eyes, indicating that the steroid implant can be a valuable option for managing refractory DME, despite the overall visual outcomes being modest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory diabetic macular edema with a fluocinolone acetonide implant in vitrectomized and non-vitrectomized eyes. La Mantia, A., Hawrami, A., Laviers, H., et al.[2020]

In a study of 41 eyes from 30 patients with diabetic macular edema (DME), the 0.19-mg fluocinolone acetonide (FAc) implant showed significant functional improvements, with 73% of patients experiencing enhanced vision and 54% achieving complete resolution of DME after 12 months.

Vitrectomized patients demonstrated better structural outcomes, including lower central foveal thickness and fewer hyperreflective dots compared to nonvitrectomized patients, indicating that the FAc implant may be particularly effective in those who have undergone vitrectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant. Pessoa, B., Ferreira, A., Leite, J., et al.[2022]

In a case study of a patient with diabetic macular edema (DME) who did not respond to laser treatment or anti-VEGF therapy, the fluocinolone acetonide (FAc) implant led to significant improvements in both edema and visual acuity.

The results suggest that if a patient is unresponsive to anti-VEGF therapy in one eye, switching to a corticosteroid implant like FAc in the other eye may be a beneficial alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Patient with Diabetic Macular Edema Receiving Fluocinolone Acetonide Intravitreal Implant. Bertelmann, T., Schulze, S.[2020]

In a study of 10 eyes from 7 patients with macular edema due to chronic non-infectious uveitis, the fluocinolone acetonide intravitreal implant (FAc) significantly improved best-corrected visual acuity (BCVA) starting at 6 months and reduced central macular thickness (CMT) persistently over 12 months.

The FAc implant was found to be safe, with no adverse events reported during the year-long study, indicating it is a viable treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 0.19 mg Fluocinolone Acetonide Implant in Non-infectious Posterior Uveitis Evaluated as Area Under the Curve. Battista, M., Starace, V., Cicinelli, MV., et al.[2022]

A 52-year-old woman with severe Sjögren's syndrome-related keratopathy showed significant improvement in her left eye after receiving an off-label intravitreal fluocinolone acetonide implant, with no further surgical interventions needed over a 6-month follow-up period.

In contrast, her right eye continued to experience complications requiring multiple surgeries, suggesting that fluocinolone acetonide may be an effective treatment option for severe autoimmune corneal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's syndrome-related keratopathy: a case report. Wasielica-Poslednik, J., Pfeiffer, N., Gericke, A.[2020]

The study presents a novel and safe technique for removing a dislocated fluocinolone acetonide (FAc) implant from the anterior chamber of the eye and successfully reinserting it into the vitreous cavity, demonstrated in two patients without complications.

After two months, the reinserted FAc implant remained in the vitreous cavity, indicating the effectiveness of the technique in preserving the integrity of the implant and preventing damage to the eye.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Technique for Repositioning of a Migrated ILUVIEN(®) (Fluocinolone Acetonide) Implant into the Anterior Chamber. El-Ghrably, IA., Saad, A., Dinah, C.[2020]

The phase III BALATON/COMINO trials will assess the efficacy and safety of faricimab in treating diabetic macular edema due to retinal vein occlusion, involving 1282 patients across 22 countries.

Faricimab is being compared to aflibercept using a personalized treatment approach that adjusts dosing intervals based on individual patient responses, aiming to demonstrate noninferiority in visual acuity outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale. Hattenbach, LO., Abreu, F., Arrisi, P., et al.[2023]

Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) is effective for treating diabetic macular oedema (DMO) in patients who did not respond well to conventional treatments, providing a sustained release of medication over 3 years.

The implant is also indicated for non-infectious posterior uveitis and off-label for macular oedema due to retinal vein occlusion, highlighting its versatility in managing various retinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Fluocinolone Acetonide Implant (ILUVIEN®) for the Treatment of Retinal Conditions. A Review of Clinical Studies. Mushtaq, Y., Mushtaq, MM., Gatzioufas, Z., et al.[2023]

Faricimab is a bispecific antibody that targets both VEGF-A and Ang-2, and it has been approved in the USA for treating neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

The drug is administered via intravitreal injection and is currently undergoing Phase III clinical trials for additional retinal vascular diseases, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faricimab: First Approval. Shirley, M.[2022]

The study found that withdrawing and storing the therapeutic antibody faricimab in specialized syringes for up to 37 days did not affect its structural integrity or bi-specific binding properties, ensuring its efficacy as a treatment.

Analyses showed no signs of degradation or aggregation of faricimab, indicating that it remains stable and effective for use in intravitreal injections during the storage period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties. Jørstad, ØK., Foss, S., Gjølberg, TT., et al.[2023]

Faricimab treatment significantly extended the recurrence interval of diabetic macular edema (DME) in patients previously treated with ranibizumab or aflibercept, increasing from an average of 5.8 weeks to 10.8 weeks, with 44.4% of patients achieving a recurrence interval of 12 weeks or more.

The study, involving 18 patients over a follow-up period of at least 4 months, found no serious adverse events associated with faricimab, suggesting it is a safe option for patients with refractory DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept. Ohara, H., Harada, Y., Hiyama, T., et al.[2023]

Faricimab, a bispecific antibody, showed non-inferior efficacy compared to aflibercept in improving best-corrected visual acuity in patients with neovascular age-related macular degeneration (nAMD) over two phase 3 trials involving 1329 patients.

The trials demonstrated that faricimab can be administered up to every 16 weeks, potentially reducing the treatment burden for patients while maintaining similar safety profiles to aflibercept, with comparable rates of ocular adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Heier, JS., Khanani, AM., Quezada Ruiz, C., et al.[2023]

Citations

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2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602697/

Clinical Review - Faricimab (Vabysmo) - NCBI Bookshelf Secondary outcomes included the frequency of administration of faricimab, retinal thickness, retinal fluids, pigment epithelial detachment (PED), and vision- ...

3. roche.com roche.com/media/releases/med-cor-2021-02-12

New phase III data show Roche's faricimab is the first ... “These faricimab data offer the promise of a new treatment for two common causes of blindness, diabetic macular edema and neovascular age- ...

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761235Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov Safety of Faricimab (RO6867461) in Patients with Diabetic Macular Edema. 6.3.1. Study Design. Primary Objective: Evaluate the efficacy of ...