A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7446603 Administered Alone or in Combination With Aflibercept or Faricimab in Participants With Diabetic Macular Edema
- Conditions
- Diabetic Macular Edema
- Interventions
- Registration Number
- NCT06850922
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 546
- Documented diagnosis of diabetes mellitus (DM) (Type 1 or Type 2) with glycated hemoglobin (HbA1c) < 12%
- Macular thickening secondary to DME involving the center of the fovea > 325 microns
- Decreased VA attributable primarily to DME between 25 and 73 ETDRS letters
- Currently untreated DM or previously untreated participants who initiated oral anti-diabetic medication or insulin within 90 days prior to Day 1
- Uncontrolled blood pressure (BP)
- Pregnancy or breastfeeding, or intention to become pregnant during the study
- For Parts 1-4: IVT anti-VEGF treatment within 90 days prior to Day 1; For Part 5: IVT anti-VEGF treatment within 120 days prior to Day 1 or IVT anti-VEGF treatment prior to Day 1 for treatment naïve participants
- Treatment with SUSVIMOTM (ranibizumab injection) prior to Day 1
- Any IVT or periocular (sub-tenons) corticosteroid treatment within 6 months prior to Day 1
- Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision
- Proliferative diabetic retinopathy (PDR) in the study eye
- Active or history of uveitis, vitritis (grade trace or above), and/or scleritis in either eye Other protocol-specified inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Single Ascending Dose (SAD) Stage RO7446603 Participants received a single dose of RO7446603 at five different dose levels as IVT injection on Day 1. Part 2: Multiple Dose (MD) Monotherapy Stage RO7446603 Participants received four different dose levels of RO7446603 (two doses at each planned dose level) as IVT injection, every 8 weeks (Q8W). Part 3: MD Co-administration With Aflibercept Stage RO7446603 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). Part 3: MD Co-administration With Aflibercept Stage Aflibercept 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). Part 4: MD Co-administration With Faricimab Stage Faricimab 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. Part 5: MD Co-mixed With Faricimab Stage Faricimab 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. Part 4: MD Co-administration With Faricimab Stage RO7446603 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. Part 5: MD Co-mixed With Faricimab Stage RO7446603 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.
- Primary Outcome Measures
Name Time Method Parts 1-5: Percentage of Participants With Adverse Events (AEs) From study start through end of study (Up to approximately 58 months) Parts 1-5: Percentage of Participants With Ocular AEs From study start through end of study (Up to approximately 58 months) Part 1: Change in Best Corrected Visual Acuity (BCVA) Over Time From Baseline up to Week 16 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.
Parts 2-4: Change in BCVA Over Time From Baseline up to Week 28 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.
Part 5: Change From Baseline in BCVA Averaged Over Weeks 52 and 56 From Baseline up to Week 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.
- Secondary Outcome Measures
Name Time Method Part 5: Proportion of Participants Gaining ≥ 15 Letters in BCVA From Baseline Averaged Over Weeks 52 and 56 From Baseline up to Week 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.
Part 5: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time From Baseline up to Week 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.
Part 5: Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time From Baseline up to Week 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.
Parts 1-4: Serum Concentration of RO7446603 Total Fab 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 From study start through end of study (Up to approximately 58 months) Part 5: Change From Baseline in BCVA Score Over Time From Baseline up to Week 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.
Parts 1-5: Number of Participants With Serum Treatment-emergent Anti-drug Antibody (ADA) Formation to RO7446603 From study start through end of study (Up to approximately 58 months)
Related Research Topics
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Trial Locations
- Locations (53)
Barnet Dulaney Perkins Eye Center
🇺🇸Phoenix, Arizona, United States
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
Associated Retinal Consultants PC
🇺🇸Phoenix, Arizona, United States
Retinal Consultants of Arizona
🇺🇸Phoenix, Arizona, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Retinal Consultants Medical Group
🇺🇸Sacramento, California, United States
Northern California Retina-Vitreous Associates
🇺🇸Mountain View, California, United States
Macula Retina Vitreous Research Institute
🇺🇸Torrance, California, United States
Retina Specialists of Colorado
🇺🇸Aurora, Colorado, United States
Retina Consultants of Southern Colorado PC
🇺🇸Colorado Springs, Colorado, United States
Advanced Vision Research Institute
🇺🇸Longmont, Colorado, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Blue Ocean Clinical Research
🇺🇸Clearwater, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Retina Associates of Florida;Retina Associates of Florida
🇺🇸Tampa, Florida, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
University Retina and Macula Associates, PC
🇺🇸Lemont, Illinois, United States
Raj K. Maturi, MD PC
🇺🇸Indianapolis, Indiana, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
Cumberland Valley Retina Consultants
🇺🇸Hagerstown, Maryland, United States
Long Island Vitreoretinal Consultants;Opthalmology
🇺🇸Hauppauge, New York, United States
Western Carolina Retinal Associate PA
🇺🇸Asheville, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Graystone Eye
🇺🇸Hickory, North Carolina, United States
Piedmont Retina Specialists
🇺🇸Winston-Salem, North Carolina, United States
Cincinnati Eye Institute
🇺🇸Blue Ash, Ohio, United States
Ohio State Eye and Ear Institute
🇺🇸Columbus, Ohio, United States
Tulsa Retina Consultants
🇺🇸Tulsa, Oklahoma, United States
Cascade Medical Research Institute LLC
🇺🇸Springfield, Oregon, United States
Erie Retina Research
🇺🇸Erie, Pennsylvania, United States
Sewickely Eye Group
🇺🇸Sewickley, Pennsylvania, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Texas Retina Associates
🇺🇸Dallas, Texas, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Austin Clinical Research LLC
🇺🇸Austin, Texas, United States
Retina & Vitreous of Texas
🇺🇸Bellaire, Texas, United States
Valley Retina Institute P.A.
🇺🇸McAllen, Texas, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retina Consultants of Texas - San Antonio
🇺🇸San Antonio, Texas, United States
Brown Retina Institute
🇺🇸San Antonio, Texas, United States
Retina Consultants of Texas
🇺🇸The Woodlands, Texas, United States
Strategic Clinical Research Group, LLC
🇺🇸Willow Park, Texas, United States
Retina Associates of Utah, PLLC;Clinical Research
🇺🇸Salt Lake City, Utah, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Wagner Kapoor Institute
🇺🇸Norfolk, Virginia, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Emanuelli Research and Development Center LLC
🇵🇷Arecibo, Puerto Rico