RO7446603 + Aflibercept/Faricimab for Diabetic Macular Edema

(THAMES Trial)

Recruiting at 73 trial locations

Overseen By Reference Study ID Number: GR43828 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genentech, Inc.

Must not be taking: Anti-VEGF, Corticosteroids

Disqualifiers: Untreated diabetes, Uncontrolled blood pressure, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

546 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for diabetic macular edema (DME), a condition that causes vision problems due to fluid buildup in the eye. Researchers aim to assess the effectiveness of the new drug, RO7446603 (an experimental treatment), both alone and in combination with existing drugs, aflibercept and faricimab. Currently in Phase II, the study tests different doses of RO7446603 mixed with faricimab to evaluate its safety and effectiveness. This trial may suit individuals with diabetes who experience vision issues primarily due to DME and have controlled blood sugar and blood pressure levels. As a Phase II trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had certain eye treatments like IVT anti-VEGF or corticosteroids within specific time frames before starting the trial.

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

Research is investigating a drug called RO7446603 for treating diabetic macular edema, specifically assessing its safety when injected into the eye. In earlier studies, patients received RO7446603 either alone or with other treatments like aflibercept or faricimab. These studies aimed to evaluate patient tolerance and bodily reactions to the drug. The results showed that the treatment was generally well-tolerated, though some patients experienced common side effects like eye irritation or discomfort from the injections.

For aflibercept, studies have found that serious side effects are rare but can include allergic reactions and retinal detachment, which occurs when the retina pulls away from the back of the eye. This happens in less than 1% of patients. Faricimab is also being tested with RO7446603 to assess its safety and patient tolerance.

Since this trial is in the early stages, the main focus is on ensuring the drugs are safe and understanding their effects in the body. Overall, the treatments appear safe, but like any medical treatment, there are risks of side effects. It's important to discuss any concerns with a doctor and understand the potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RO7446603 for diabetic macular edema because it offers a fresh approach compared to standard treatments like Aflibercept and Faricimab alone. Unlike typical therapies, RO7446603 is designed to be administered via intravitreal injection and works by targeting a new pathway that may enhance the effectiveness of existing drugs. This innovative method could potentially improve outcomes by allowing for less frequent dosing and better long-term eye health. Additionally, the possibility of co-administration with Aflibercept or Faricimab suggests a synergistic effect, which might result in more significant improvements in vision for patients.

What evidence suggests that this trial's treatments could be effective for diabetic macular edema?

Research has shown that RO7446603 targets the Tie2 pathway, which plays a crucial role in maintaining blood vessel stability and reducing leakage. This mechanism could help manage diabetic macular edema (DME) by decreasing fluid buildup in the eye. Early results suggest this approach might be effective. In this trial, some participants will receive RO7446603 alone, while others will receive it combined with either faricimab or aflibercept. Past studies have demonstrated that faricimab improves vision and eye health in DME patients. Combining RO7446603 with faricimab or aflibercept might enhance these benefits due to their complementary actions. Although further research is necessary to confirm these effects, the initial signs are promising. ^{2 3 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for individuals with diabetic macular edema, a condition that affects the retina in people with diabetes. Participants should be adults who can safely receive eye injections and have not had any recent eye surgery or other treatments that might interfere with the study.

Inclusion Criteria

I have diabetes with an HbA1c level below 12%.

My vision loss is mainly due to diabetic macular edema.

My eye condition is due to diabetes and affects the center of my vision.

Exclusion Criteria

Pregnancy or breastfeeding, or intention to become pregnant during the study

My study eye has advanced diabetic eye disease.

I have or had inflammation in my eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants received single and multiple intravitreal doses of RO7446603 as monotherapy or co-administered with aflibercept or faricimab

28 weeks

Multiple visits for dosing and monitoring

Phase II Treatment

Participants receive RO7446603 in combination with faricimab, co-mixed and administered as a single IVT injection

56 weeks

Regular visits for dosing every 4 weeks initially, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept
• Faricimab
• RO7446603

Trial Overview The study tests RO7446603 alone or combined with Aflibercept or Faricimab to see if they're safe and effective for treating diabetic macular edema. It's given as an injection into the eye, comparing different doses and combinations.

How Is the Trial Designed?

Group I: Part 5: MD Co-mixed With Faricimab Stage Experimental Treatment 2 Interventions

Participants will receive two different dose levels of RO7446603 (co-mixed with faricimab or faricimab alone) as IVT injection, Q4W for the first six doses followed by Q8W for four doses.

Group II: Part 4: MD Co-administration With Faricimab Stage Experimental Treatment 2 Interventions

Participants received a single dose of faricimab followed by a 4-week enrichment screening period. Eligible participants received two different dose levels (two doses at each planned dose level) of RO7446603 as IVT injection, Q8W, along with three doses of faricimab (co-administered with RO7446603 or alone) as IVT injection, Q4W.

Group III: Part 3: MD Co-administration With Aflibercept Stage Experimental Treatment 2 Interventions

Participants received two different dose levels (two doses at each planned dose level) of RO7446603 as IVT injection, Q8W along with four doses of aflibercept IVT injections, every 4 weeks (Q4W).

Group IV: Part 2: Multiple Dose (MD) Monotherapy Stage Experimental Treatment 1 Intervention

Participants received four different dose levels of RO7446603 (two doses at each planned dose level) as IVT injection, every 8 weeks (Q8W).

Group V: Part 1: Single Ascending Dose (SAD) Stage Experimental Treatment 1 Intervention

Participants received a single dose of RO7446603 at five different dose levels as IVT injection on Day 1.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead 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

Published Research Related to This Trial

In a study of anti-VEGF naïve patients with clinically significant diabetic macular edema (DME), intravitreal aflibercept significantly improved best-corrected visual acuity (BCVA) after 12 months, with all patients showing improvement and 89.6% gaining 10 or more ETDRS letters.

Aflibercept also led to a significant reduction in central macular thickness, from an average of 460.5 μm at baseline to 229.0 μm at 12 months, with no adverse events reported, supporting its safety and efficacy as a first-line treatment for DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for clinically significant diabetic macular edema: 12-month results in daily clinical practice. Campos Polo, R., Rubio Sánchez, C., García Guisado, DM., et al.[2022]

In a study of 221 treatment-naïve patients with diabetic macula oedema treated with Aflibercept over 12 months, the average visual acuity gain was only 4.0 letters, which is significantly lower than outcomes reported in the VIVID and VISTA clinical trials.

The NWL cohort had worse baseline health indicators, such as higher HbA1c levels and more advanced diabetic retinopathy, which likely contributed to their lower treatment effectiveness compared to the clinical trial participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for treatment-naïve diabetic macula oedema in a multi-ethnic population: Real-world outcomes from North West London. Dinah, C., Ghulakhszian, A., Sim, SY., et al.[2021]

In a study of 25 eyes with refractory diabetic macular edema (DME) that had not improved after multiple treatments with ranibizumab or dexamethasone, switching to aflibercept resulted in a significant mean visual acuity gain of +8 letters after 6 months (p = 0.01).

Additionally, there was a notable reduction in central retinal thickness from 470.8 μm to 303.3 μm (p = 0.001), indicating both functional and anatomical improvements after the switch to aflibercept.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant. Herbaut, A., Fajnkuchen, F., Qu-Knafo, L., et al.[2022]

Faricimab is a new bispecific antibody that targets both angiopoietin-2 and VEGF, which may enhance treatment durability and improve outcomes for patients with diabetic macular edema (DME).

The YOSEMITE and RHINE trials, involving 940 and 951 participants respectively, are the first to use a personalized treatment interval (PTI) approach, allowing for flexible dosing up to every 16 weeks, aimed at maximizing therapeutic results while reducing treatment burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale. Eter, N., Singh, RP., Abreu, F., et al.[2022]

In a study of 51 treatment-resistant diabetic macular edema patients, switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) resulted in significantly better outcomes, with 37.5% of the IVF group achieving a central macular thickness (CMT) of less than 300 µm compared to only 3.7% in the control group (p=0.001).

The IVF group also showed greater improvements in visual acuity, with 41.7% gaining two or more lines of vision compared to 11.1% in the control group (p=0.01), indicating that IVF may be a more effective option for patients who did not respond well to IVA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faricimab for Treatment-Resistant Diabetic Macular Edema. Rush, RB., Rush, SW.[2022]

Aflibercept therapy significantly improved visual acuity and reduced central retinal thickness in 100% of treatment-naïve patients with diabetic macular edema (DME) after just three injections, with maximum improvement observed after six injections.

In patients who were previously unresponsive to ranibizumab, aflibercept also restored retinal morphology and improved visual function in 55% of cases, demonstrating its effectiveness as a second-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-VEGF therapy for diabetic macular edema. From theory to clinical practice]. Fursova, AZ., Chubar, NV., Tarasov, MS., et al.[2019]

In a study of 72 patients with diabetic macular edema (DME) who were resistant to previous treatments with ranibizumab or bevacizumab, 58.3% showed a positive response to three monthly injections of aflibercept, indicating its efficacy in this challenging patient group.

The treatment significantly improved visual acuity and reduced central foveal thickness in responders, but vitrectomized eyes had a notably lower response rate, suggesting that prior surgical intervention may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Aflibercept for Patients With Diabetic Macular Edema Refractory to Bevacizumab or Ranibizumab: Analysis of Response to Aflibercept. Chen, YY., Chang, PY., Wang, JK.[2022]

In a study of 94 patients with diabetic macular edema (DME), intravitreal aflibercept injections significantly improved best-corrected visual acuity (BCVA) by an average of +7.4 letters after 36 months, with treatment-naive patients showing even greater improvement (+8.9 letters).

The treatment was found to be safe, with only mild, non-sight-threatening ocular adverse events reported, indicating that aflibercept is a viable option for managing DME in a real-life setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study. Chatziralli, I., Agapitou, C., Dimitriou, E., et al.[2023]

In a study of 49 eyes from 34 patients with diabetic macular edema (DME) who did not respond to bevacizumab, switching to aflibercept led to significant improvements in both visual acuity (from 0.55 to 0.46 logMAR) and reduction in central macular thickness (from 473 to 349 μm).

The results showed that patients with poorer vision before switching to aflibercept experienced greater improvements, indicating that pre-switch central macular thickness can predict the effectiveness of aflibercept treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success. Laiginhas, R., Silva, MI., Rosas, V., et al.[2018]

Aflibercept treatment for diabetic macular edema (DME) led to significant improvements in best-corrected visual acuity (BCVA) and reductions in central subfield retinal thickness (CST) across all morphological types of DME over a one-year period, with 115 patients included in the study.

The treatment was most effective in the diffuse retinal thickening (DRT) group, requiring fewer injections to achieve similar outcomes compared to the cystoid macular edema (CME) and serous retinal detachment (SRD) groups, which needed more injections for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Optical Coherence Tomography Patterns on One-year Outcomes of Aflibercept Therapy for Diabetic Macular Edema. Ozcaliskan, S., Balci, S., Karasu, B., et al.[2020]

In a study of 46 patients with diabetic macular edema and subfoveal retinal detachment, intravitreal aflibercept showed a higher rate of complete resolution of retinal detachment compared to ranibizumab after 12 months (100% vs 80.8%).

Both treatments were effective in improving anatomical and functional outcomes, but there was no significant difference in visual acuity improvement between the two groups throughout the 12-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of aflibercept and ranibizumab in diabetic macular edema associated with subretinal detachment. Ozkaya, A., Demir, G., Kirmaci, A.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06850922

NCT06850922 | A Study to Evaluate the Safety, Tolerability ... This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular edema (DME).

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/eye-disorder/dme/a-study-to-evaluate-the-safety--tolerability--pharmacok-19095.html

Clinical trial for Diabetic Macular Edema-Genentech A Mem... This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular edema (DME).

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/579719

A Study to Evaluate the Safety, Tolerability ... This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular ...

4. medically.gene.com medically.gene.com/global/en/unrestricted/ophthalmology/ASRS-2025/asrs-2025-presentation-brown-a-phase-1-study-to-evaluat.html

A phase 1 study to evaluate the Tie2 agonist RO7446603 ... A phase 1 study to evaluate the Tie2 agonist RO7446603 (RG6351), alone or in combination with aflibercept 2 mg or faricimab▽ 6 mg, in diabetic macular edema.

5. withpower.com withpower.com/trial/phase-2-macular-edema-5-2022-246fd

RO7446603 + Aflibercept/Faricimab for Diabetic Macular ... This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular edema (DME).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06850922

NCT06850922 | A Study to Evaluate the Safety, Tolerability ... This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular edema (DME).

7. isrctn.com isrctn.com/pdf/14152148

Study of the safety, tolerability, processing by RO7446603 may lead to stabilization of the diseased blood vessels and improve visual and structural. (anatomical) outcomes in DME compared with ...