Faricimab for Diabetic Macular Edema

(INSITE-DME Trial)

Not currently recruiting at 50 trial locations

Overseen By Veeral Sheth, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: McMaster University

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

Disqualifiers: Ocular inflammation, High-risk retinopathy, Glaucoma, 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

Compensation: Varies

Number of Visits: 8

Duration: 100 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using faricimab injections to treat diabetic macular edema, a condition where fluid accumulates in the retina, leading to vision problems for people with diabetes. The study compares two treatment plans: one with an injection schedule that adjusts based on eye assessments, and another with regular, fixed appointments. Individuals with diabetes experiencing vision issues due to macular swelling might be suitable candidates for this trial. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a 12-week washout period required for previous anti-VEGF treatments before starting the trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but there is a washout period of 12 weeks for previous anti-VEGF treatments before starting the trial.

What is the safety track record for Faricimab?

Research has shown that faricimab is generally safe for patients. It has been used effectively to treat diabetic macular edema, a condition that causes swelling in the eye. In studies, participants who received regular doses of faricimab experienced improvements in vision and a decrease in eye swelling.

Most people tolerate faricimab well, though some have reported mild side effects such as eye redness, discomfort, or increased tearing. Serious side effects are rare. The FDA has approved faricimab for other eye conditions, supporting its safety.

For those considering joining a trial with faricimab, research suggests it is a safe option for treating diabetic macular edema. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about faricimab for diabetic macular edema because it offers a new approach in comparison to existing treatments like anti-VEGF therapies such as ranibizumab and aflibercept. Unlike these standard options, faricimab targets two pathways: it blocks both VEGF-A, a molecule that promotes blood vessel growth, and Ang-2, which contributes to blood vessel instability. This dual-action mechanism has the potential to provide more comprehensive control of the condition, possibly leading to longer-lasting effects and reducing the frequency of injections needed over time. This could mean fewer clinic visits and improved convenience for patients.

What is the effectiveness track record for faricimab in treating diabetic macular edema?

Research has shown that faricimab improves vision and reduces fluid build-up in the eyes of people with diabetic macular edema. Clinical studies have demonstrated lasting vision improvements with faricimab. Patients experienced significant vision gains and reduced eye fluid over time. These positive results suggest that faricimab can offer long-term vision benefits for those with this eye condition. Participants in this trial will receive faricimab either through a "Treat and Extend" approach or as part of a "Control/Usual Care" arm, both involving regular intravitreal injections. Faricimab is already approved for use, highlighting its proven effectiveness in treating diabetic macular edema. ^{1 2 3 6 7}

Who Is on the Research Team?

Dr. Varun Chaudhary, MD, FRCS(C)

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

Adults over 18 with diabetes (type 1 or type 2) and diabetic macular edema affecting the central vision, who have a certain level of visual impairment. Participants must have stable blood sugar control with an HbA1c under 10%. They should not have had recent eye surgery, ocular inflammation, infections, uncontrolled glaucoma, or previous treatments that could affect the trial's outcome.

Inclusion Criteria

Hemoglobin A1c must be <10% within 2 months prior to 1st study treatment

My eye scan shows swelling in the center due to diabetes.

Provide signed informed consent

Exclusion Criteria

Anticipated problems, in the judgment of the site investigator, maintaining compliance with the protocol, including attending study visits, completing assessments or procedures

My eye swelling is not due to diabetic macular edema.

Known hypersensitivity to faricimab or any of the excipients in the faricimab injection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive faricimab intravitreal injections with varying intervals based on treatment arm until week 100

100 weeks

Monthly visits initially, then every 8 weeks or adjusted based on assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Faricimab
• Faricimab Injection

Trial Overview The study is testing Faricimab for diabetic macular edema by comparing two approaches: 'treat & extend' where treatment intervals may be adjusted based on disease activity versus a fixed schedule of doses regardless of changes in symptoms.

How Is the Trial Designed?

Group I: Treat and Extend Experimental Treatment 1 Intervention

Participants randomized to the T\&E Arm will initially receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), with treatment intervals increased/extended, reduced, or maintained based on CST assessments, until week 100.

Group II: Control/Usual Care Arm Experimental Treatment 1 Intervention

Participants in the control arm will receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), for 6 treatments. Afterwards, participants will continue to receive 6mg faricimab IVT every 8 weeks until week 100.

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?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

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 a study of 482 patients with reversible obstructive airways disease, both formoterol (12 micrograms b.i.d.) and salmeterol (50 micrograms b.i.d.) demonstrated similar long-term efficacy in improving morning peak expiratory flow (PEF) over a 6-month treatment period.

Formoterol showed a trend towards better evening PEF results compared to salmeterol at 2, 3, and 4 months, but overall, both medications had comparable safety profiles with no significant differences in adverse events or use of rescue medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease. Vervloet, D., Ekström, T., Pela, R., et al.[2019]

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]

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]

In a study of 51 patients with treatment-resistant diabetic macular edema (DME), switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) resulted in significant improvements, with 39.2% achieving a treatment interval of 8 weeks or more and a fluid-free macula after 12 months.

The central macular thickness (CMT) decreased significantly from 400.2 microns to 340.6 microns, and 21.6% of patients experienced a visual acuity improvement of 3 lines or more, indicating that IVF may be an effective alternative for patients not responding to IVA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One Year Results of Faricimab for Aflibercept-Resistant Diabetic Macular Edema. Rush, RB.[2023]

In a phase 1 study involving 72 healthy adults, the budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) demonstrated similar pharmacokinetic profiles to the budesonide/formoterol fumarate metered dose inhaler (BFF MDI), indicating bioequivalence for the active ingredients.

All inhaler treatments were well tolerated, and despite higher systemic exposure to budesonide and formoterol with BGF MDI and BFF MDI compared to the dry powder inhaler (BUD/FORM DPI), there were no significant differences in adverse events, suggesting a comparable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Co-Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed-Dose Combinations Compared With an Active Control: A Phase 1, Randomized, Single-Dose, Crossover Study in Healthy Adults. Maes, A., DePetrillo, P., Siddiqui, S., et al.[2020]

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]

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 22 trials with 16,486 participants, vilanterol/umeclidinium was found to be the most effective LABA/LAMA fixed-dose combination for improving lung function in COPD, while formoterol/aclidinium showed the least efficacy.

All LABA/LAMA combinations had similar safety profiles, indicating that while efficacy varied, the safety of these treatments was consistent across different medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative analysis of efficacy and safety of LABA/LAMA fixed-dose combinations in the treatment of stable COPD. Gong, Y., Lv, Y., Liu, H., et al.[2022]

In a study involving 11,404 patients with chronic obstructive pulmonary disease (COPD), the fixed-dose combination of indacaterol and glycopyrronium (QVA149) showed no significant increase in the risk of death or serious cardiovascular events compared to placebo.

QVA149 demonstrated a comparable safety profile to its individual components (indacaterol and glycopyrronium) and tiotropium, indicating it is a safe treatment option for COPD without raising concerns for major adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients. Wedzicha, JA., Dahl, R., Buhl, R., et al.[2020]

Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) in fixed-dose combinations (FDCs) do not significantly increase the risk of cardiovascular serious adverse events (SAEs) compared to their individual components or placebo, indicating a favorable safety profile for COPD patients.

Among the FDCs studied, aclidinium/formoterol and tiotropium/olodaterol were found to be the safest options, while some combinations involving glycopyrronium were associated with higher risks, highlighting the importance of careful selection in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis. Rogliani, P., Matera, MG., Ora, J., et al.[2022]

Citations

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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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03622593

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3. roche.com roche.com/media/releases/med-cor-2020-12-21

Roche's faricimab meets primary endpoint and shows ... “These positive results show that faricimab has the potential to offer lasting vision improvements for people with diabetic macular edema, while ...

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Genentech: Press Releases | Sunday, Dec 20, 2020 Genentech's Faricimab meets primary endpoint and shows strong durability across two global Phase III studies for diabetic macular edema, a leading cause of ...

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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 ...