Vabysmo for Diabetic Retinopathy

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must not be taking: Ocular anti-VEGF

Disqualifiers: Pregnancy, Glaucoma, Uveitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests faricimab (Vabysmo) for individuals with complications from diabetic retinopathy, such as persistent vitreous hemorrhage or retinal detachment. The study aims to determine if faricimab can reduce these complications during eye surgery. Participants will receive either the actual treatment or a sham procedure. The trial seeks individuals with diabetic retinopathy-related eye bleeding who are scheduled for vitrectomy. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using any ocular anti-VEGF treatments, you must stop them at least 3 months before starting the trial.

What is the safety track record for Faricimab?

Research has shown that faricimab, the treatment being tested in this trial, is generally safe for humans. Other studies reported common side effects, such as cataracts (clouding of the eye lens) in about 10% of patients and bleeding in the white of the eye in about 7% of patients. However, most people experience these side effects as mild. Since the FDA has already approved faricimab for similar eye conditions, it is considered safe enough for regular use in those cases. Overall, while some side effects exist, faricimab has proven relatively safe for many patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Faricimab is unique because it targets both Angiopoietin-2 (Ang-2) and Vascular Endothelial Growth Factor-A (VEGF-A), which are key players in the progression of diabetic retinopathy. Most current treatments, like ranibizumab and aflibercept, primarily focus on inhibiting VEGF-A alone. By addressing both Ang-2 and VEGF-A, faricimab has the potential to offer improved outcomes in controlling and treating the condition. Researchers are excited about this dual-action approach because it may lead to better stabilization of blood vessels in the retina and reduce the frequency of injections needed compared to existing therapies.

What is the effectiveness track record for Vabysmo in treating diabetic retinopathy?

Research has shown that faricimab, also known as Vabysmo, effectively treats diabetic retinopathy. Studies have found that it can improve vision and reduce retinal swelling. In this trial, participants will receive either faricimab or a sham injection at random. Faricimab has led to significant improvements in eye health and vision, known for reducing diabetic eye conditions. Long-term studies support these benefits, showing lasting results over time. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-clearing vitreous hemorrhage due to diabetic retinopathy, who are undergoing eye surgery. They must be able to follow the study plan and use effective contraception if of childbearing potential. Those unable to commit or at risk of not complying with contraceptive guidelines are excluded.

Inclusion Criteria

I have a severe eye condition due to diabetes and need surgery.

Exclusion Criteria

General exclusion criteria: Known hypersensitivity to components in the faricimab injection, dilating eye drops, disinfectants, anesthetics, or antimicrobial preparations used during the study, History of diseases or conditions contraindicating the use of faricimab, Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab. Women of childbearing potential must have negative pregnancy tests at specified time points.

My study eye has not had recent treatments or surgeries, and only has diabetic retinopathy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive peri-operative faricimab or sham injection to evaluate efficacy in limiting complications from pars plana vitrectomy

6 months

Intra-operative and post-operative visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including BCVA outcomes and rates of post-operative complications

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Faricimab

Trial Overview The study tests whether Vabysmo (Faricimab) injections before eye surgery can reduce complications compared to a sham treatment in patients with diabetic-related bleeding in the eye. Participants will be randomly assigned to receive either the real drug or a placebo.

How Is the Trial Designed?

Group I: Faricimab injection Experimental Treatment 1 Intervention

Patients will be randomized 2:1 to receive either farcimab (6 mg from 0.05 mL of a 120 mg/mL) or sham injection. The 6-mg dose of faricimab will be administered by IVT at the study site to patients. A specified filter needle must be used for each dose preparation of faricimab according to the instructions provided in the Investigator's Brochure and package insert. No other material than specified should be used. Vials of faricimab drug product are for a single-dose only (one injection preparation per patient per eye). Vials used for one patient must not be used for any other patient. Partially used vials, remaining faricimab drug product, as well as administration material must not be reused.

Group II: Sham injection Placebo Group 1 Intervention

Patients will be randomized 2:1 to receive either farcimab (6 mg from 0.05 mL of a 120 mg/mL) or sham injection. The sham procedure mimics an intravitreal injection of faricimab except that the blunt end of an empty syringe is pressed against an anesthetized eye instead of a needle attached to a faricimab-filled syringe.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

Faricimab demonstrated significant improvements in best-corrected visual acuity (BCVA) for patients with diabetic macular edema, with similar efficacy observed in both Asian (average gain of +10.4 letters) and non-Asian (average gain of +11.1 letters) subgroups after one year.

The treatment was well tolerated with no new safety concerns, and a high percentage of patients in both groups achieved extended dosing intervals, indicating the durability of the treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Durability, and Safety of Faricimab in Patients From Asian Countries With Diabetic Macular Edema: 1-Year Subgroup Analysis of the Phase III YOSEMITE and RHINE Trials. Ishida, S., Chen, SJ., Murata, T., 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]

In a study of 26 patients with neovascular age-related macular degeneration (nAMD), switching to intravitreal faricimab resulted in a significantly longer fluid-free interval compared to previous treatments with anti-VEGF agents, indicating improved efficacy.

No serious adverse events were reported, suggesting that faricimab is a safe option for patients who did not respond well to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal faricimab for neovascular age-related macular degeneration previously treated with traditional anti-VEGF compounds: a real-world prospective study. Grimaldi, G., Cancian, G., Rizzato, A., 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]

Faricimab demonstrated significant improvements in best-corrected visual acuity (BCVA) in Japanese patients with diabetic macular edema (DME), with mean changes of +11.1 letters for Q8W dosing and +8.1 letters for personalized treatment intervals, comparable to the global results.

The treatment was well tolerated with no new safety concerns, and a majority of patients in the personalized treatment interval group were able to extend dosing to every 12 or 16 weeks, indicating durable efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in Japanese patients with diabetic macular edema: 1-year results from the Japan subgroup of the phase 3 YOSEMITE trial. Shimura, M., Kitano, S., Ogata, N., et al.[2023]

In the phase 2 BOULEVARD trial involving 229 patients with diabetic macular edema, faricimab (6.0 mg) showed statistically significant improvements in visual acuity compared to ranibizumab, with an average gain of 3.6 ETDRS letters at week 24.

Faricimab also demonstrated greater reductions in central subfield thickness and longer time to re-treatment, indicating its potential for enhanced durability and efficacy in treating diabetic macular edema without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Sahni, J., Patel, SS., Dugel, PU., et al.[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]

Faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) who did not respond to other anti-VEGF therapies resulted in significant anatomical improvements, including a reduction in central subfield thickness (CST) by 18µm and intraretinal/subretinal fluid height by 89µm after switching from previous treatments.

Despite the anatomical improvements, visual acuity remained stable after switching to faricimab, indicating that while the treatment effectively reduces fluid and swelling, it does not negatively impact vision in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faricimab Effectively Resolves Intraretinal Fluid and Preserves Vision in Refractory, Recalcitrant, and Nonresponsive Neovascular Age-Related Macular Degeneration. Cheng, AM., Joshi, S., Banoub, RG., et al.[2023]

Faricimab, a dual-target antibody for VEGF-A and Ang-2, has shown comparable efficacy to monthly ranibizumab in treating neovascular age-related macular degeneration, allowing for longer intervals between injections and fewer treatments overall.

In the BOULEVARD trial, faricimab significantly improved diabetic retinopathy severity in 38.6% of patients treated with the highest dose, outperforming ranibizumab, indicating its potential for effective long-term management of diabetic macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Faricimab: from research to clinical practice]. Yusef, YN., Budzinskaya, MV., Plyukhova, AA.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03622593

NCT03622593 | A Study to Evaluate the Efficacy and ... This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601678/

Clinical Review - Faricimab (Vabysmo) - NCBI - NIH The clinician group noted that clinically meaningful outcomes include improvement in vision, reduction or resolution of macular edema, regression in Diabetic ...

3. assets.roche.com assets.roche.com/f/203780/x/8de4ac9bce/vabysmo-product-information-ro-6867461-november-2023.pdf

VABYSMO® INN: Faricimab These results were maintained at week 100. An additional key efficacy outcome in DME studies was the change in the Early Treatment. Diabetic ...

4. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2022/SR0729-Vabysmo_combined.pdf

Faricimab (Vabysmo) has previously been accepted by the FDA as an efficacy end point for assessing improvement in diabetic retinopathy. Optical Coherence Tomography. OCT is a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03823287

NCT03823287 | A Study to Evaluate the Efficacy and ... This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03622580

NCT03622580 | A Study to Evaluate the Efficacy and ... This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761235Orig1s000MedR.pdf

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 ...