RO7446603 + Aflibercept/Faricimab for Diabetic Macular Edema
(THAMES Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Genentech, Inc.
Must not be taking: Anti-VEGF, Corticosteroids
Disqualifiers: Untreated diabetes, Uncontrolled blood pressure, Pregnancy, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study aims to evaluate the ocular and systemic safety, tolerability and efficacy of RO7446603 in participants with diabetic macular edema (DME). The study consists of 2 segments: Phase I (Parts 1-4) and Phase II (Part 5). Phase I investigated the safety of RO7446603 following a single and multiple intravitreal (IVT) doses as monotherapy or co-administered with IVT aflibercept or IVT faricimab (in separate injections). Phase II will investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of two dose levels of RO7446603 in combination with faricimab, with the two drugs co-mixed and administered as a single IVT injection, compared to faricimab alone. The first participant was enrolled in the Phase I segment on June 22, 2022. Phase I has been completed.
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.
What data supports the effectiveness of the drug combination RO7446603, Aflibercept, and Faricimab for treating diabetic macular edema?
Research shows that Faricimab, one of the drugs in the combination, is effective in treating diabetic macular edema by targeting specific pathways that help reduce swelling in the eye. Aflibercept, another drug in the combination, has also been shown to improve outcomes in patients with diabetic macular edema, especially those who did not respond well to other treatments.
12345Is Aflibercept safe for treating diabetic macular edema?
Research shows that Aflibercept is generally safe for treating diabetic macular edema, with studies focusing on its use in real-life practice and clinical settings.
678910How is the drug combination of RO7446603, Aflibercept, and Faricimab unique for treating diabetic macular edema?
This treatment is unique because it combines Faricimab, a bispecific antibody targeting both VEGF and angiopoietin-2, with Aflibercept, which targets VEGF alone. This dual approach aims to improve treatment durability and outcomes by addressing both angiogenic and inflammatory pathways, potentially offering better results for patients with diabetic macular edema.
1491011Eligibility Criteria
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.
+6 more
Trial Timeline
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
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Part 5: MD Co-mixed With Faricimab StageExperimental Treatment2 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 StageExperimental Treatment2 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 StageExperimental Treatment2 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 StageExperimental Treatment1 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) StageExperimental Treatment1 Intervention
Participants received a single dose of RO7446603 at five different dose levels as IVT injection on Day 1.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Georgia Retina PCMarietta, GA
Duke University Medical CenterDurham, NC
Retina Consultants of TexasThe Woodlands, TX
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Who Is Running the Clinical Trial?
Genentech, Inc.Lead Sponsor
References
Faricimab for Treatment-Resistant Diabetic Macular Edema. [2022]To assess the short-term outcomes in treatment-resistant diabetic macular edema (DME) patients changed from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF).
Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success. [2018]To evaluate functional and anatomical outcomes after aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab.
Effect of Optical Coherence Tomography Patterns on One-year Outcomes of Aflibercept Therapy for Diabetic Macular Edema. [2020]To evaluate the outcomes of aflibercept based on different morphologic patterns on optical coherence tomography (OCT) for diabetic macular edema (DME).
YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale. [2022]Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME.
Comparison of aflibercept and ranibizumab in diabetic macular edema associated with subretinal detachment. [2022]To compare the efficacy of ranibizumab and aflibercept in the treatment of diabetic macular edema associated with subfoveal retinal detachment.
Intravitreal Aflibercept for Patients With Diabetic Macular Edema Refractory to Bevacizumab or Ranibizumab: Analysis of Response to Aflibercept. [2022]To investigate the short-term efficacy and safety of intravitreal aflibercept in a case series of patients with diabetic macular edema (DME) refractory to ranibizumab or bevacizumab.
Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study. [2023]To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece.
Aflibercept for clinically significant diabetic macular edema: 12-month results in daily clinical practice. [2022]To assess the effectiveness and safety of intravitreal aflibercept in clinically significant diabetic macular edema (DME) in daily clinical practice.
Aflibercept for treatment-naïve diabetic macula oedema in a multi-ethnic population: Real-world outcomes from North West London. [2021]To evaluate the clinical outcomes of patients with treatment-naïve diabetic macula oedema (DMO) treated with Aflibercept in routine clinic settings in ethnically diverse North West London (NWL) and compare to outcomes reported in the VIVID and VISTA clinical trials.
Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant. [2022]To assess short-term functional and anatomical outcomes of refractory diabetic macular edema (DME) following a switch from ranibizumab or dexamethasone to aflibercept.
[Anti-VEGF therapy for diabetic macular edema. From theory to clinical practice]. [2019]To evaluate clinical effectiveness of aflibercept therapy for patients with diabetic macular edema (DME) - both naïve to the drug and unresponsive to previous anti-VEGF treatment.