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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
388
Participants will receive RO7446603 as an IVT injection per the schedule described in the treatment arms.
Participants will receive aflibercept as an IVT injection per the schedule described in the treatment arm.
Participants will receive faricimab as an IVT injection per the schedule described in the treatment arms.
Arizona Retina and Vitreous Consultants
Phoenix, Arizona, United States
Associated Retinal Consultants PC
Phoenix, Arizona, United States
Retinal Research Institute, LLC
Phoenix, Arizona, United States
Retina Partners of Northwest Arkansas, PLLC
Springdale, Arkansas, United States
Retinal Diagnostic Center
Campbell, California, United States
Parts 1-5: Percentage of Participants With Adverse Events (AEs)
Time frame: From study start through end of study (Up to approximately 58 months)
Parts 1-5: Percentage of Participants With Ocular AEs
Time frame: From study start through end of study (Up to approximately 58 months)
Part 1: Change in Best Corrected Visual Acuity (BCVA) Over Time
BCVA will be measured via Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity (VA) examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 16
Parts 2-4: Change in BCVA Over Time
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 28
Part 5: Change From Baseline in BCVA Averaged Over Weeks 52 and 56
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 56
Part 5: Proportion of Participants Gaining ≥ 15 Letters in BCVA From Baseline Averaged Over Weeks 52 and 56
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 56
Part 5: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 56
Part 5: Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 56
Part 5: Change From Baseline in BCVA Score Over Time
BCVA will be measured via ETDRS chart at a starting distance of 4 meters using a set of three precision VisionTM or lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The range of EDTRS is 0 to 100 letters. Higher scores indicate improvement in VA.
Time frame: From Baseline up to Week 56
Parts 1-4: Serum Concentration of RO7446603 Total Fab
Time frame: Part 1: From Baseline up to Week 16; Parts 2-4: From Baseline up to Week 28
Parts 1-5: Aqueous Humor Concentration of RO7446603 Measured as Total Fab
Time frame: From study start through end of study (Up to approximately 58 months)
Parts 1-5: Number of Participants With Serum Treatment-emergent Anti-drug Antibody (ADA) Formation to RO7446603
Time frame: From study start through end of study (Up to approximately 58 months)
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Retina Consultants of Orange County
Fullerton, California, United States
Retinal Consultants Medical Group
Modesto, California, United States
Northern California Retina-Vitreous Associates
Mountain View, California, United States
Retinal Consultants Medical Group
Sacramento, California, United States
University of California San Francisco
San Francisco, California, United States
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