Faricimab or Fluocinolone Acetonide for Vision Loss

(AL Trial)

Recruiting at 18 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

Trial Summary

What is the purpose of this trial?

This randomized controlled trial will evaluate the effect of intravitreal faricimab or fluocinolone acetonide (FAc) intravitreal implant compared with observation on long-term visual acuity following treatment of choroidal melanoma with iodine-125 plaque brachytherapy.

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.

What data supports the effectiveness of the drug Faricimab for vision loss?

Faricimab has shown excellent visual acuity improvements and strong durability in patients with diabetic macular edema and neovascular age-related macular degeneration, as demonstrated in phase III trials. It has been approved in the USA and Japan for these conditions, indicating its effectiveness in treating retinal vascular diseases. ^{1 2 3 4 5}

Is Faricimab or Fluocinolone Acetonide safe for human use?

Faricimab has been approved in the USA and Japan for treating certain eye conditions, and studies have shown it does not cause serious adverse events in patients with diabetic macular edema. The fluocinolone acetonide implant is also approved for treating vision impairment in chronic diabetic macular edema, indicating it is generally considered safe for human use. ^{1 2 6 7 8}

How is the drug Faricimab or Fluocinolone Acetonide unique for vision loss treatment?

Fluocinolone acetonide is a long-lasting implant that releases medication over three years, making it unique for treating vision loss due to diabetic macular edema and other retinal conditions, especially when other treatments have failed. ^{8 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale. [2023]

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

Faricimab: First Approval. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's syndrome-related keratopathy: a case report. [2020]

4. England pubmed.ncbi.nlm.nih.gov

A Novel Technique for Repositioning of a Migrated ILUVIEN(®) (Fluocinolone Acetonide) Implant into the Anterior Chamber. [2020]

5. England 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. [2023]

6. England 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept. [2023]

8. Switzerland 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy of 0.19 mg Fluocinolone Acetonide Implant in Non-infectious Posterior Uveitis Evaluated as Area Under the Curve. [2022]

11. China pubmed.ncbi.nlm.nih.gov

Treatment of refractory diabetic macular edema with a fluocinolone acetonide implant in vitrectomized and non-vitrectomized eyes. [2020]

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

Intravitreal Fluocinolone Acetonide Implant (ILUVIEN®) for the Treatment of Retinal Conditions. A Review of Clinical Studies. [2023]