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
- 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.
- Acronym
- THAMES
- Short title
- 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
- Official title
- A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7446603 Administered Alone or in Combination With Aflibercept or Faricimab in Patients With Diabetic Macular Edema
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Completed
- Phase
- Phase 1/Phase 2
- Study type
- Interventional
- Completion date
- 2026-06-19
- First posted
- 2025-02-28
- Registry last updated
- 2026-06-23
- Primary completion date
- 2026-05-19
- Start date
- 2022-06-22
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Genentech, Inc.
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT06850922
- ClinicalTrials.gov ID
- NCT06850922
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- Quadruple masking
- Masking description
- The Phase 1 segment of this study was open-label and participants were randomized in Part 4. The Phase 2 segment will be a randomized, double-blinded study.
- Masked roles
- Participants, Care providers, Investigators, Outcome assessors
Parts 1-5: Percentage of Participants With Adverse Events (AEs)
Timeframe: From study start through end of study (Up to approximately 58 months)
Parts 1-5: Percentage of Participants With Ocular AEs
Timeframe: From study start through end of study (Up to approximately 58 months)
Part 1: Change in Best Corrected Visual Acuity (BCVA) Over Time
Timeframe: 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
Timeframe: 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
Timeframe: 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: Proportion of Participants Gaining ≥ 15 Letters in BCVA From Baseline Averaged Over Weeks 52 and 56
Timeframe: 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
Timeframe: 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
Timeframe: 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: Change From Baseline in BCVA Score Over Time
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: From study start through end of study (Up to approximately 58 months)
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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
- Arizona Retina and Vitreous ConsultantsPhoenix, United States
- Associated Retinal Consultants PCPhoenix, United States
- Retinal Research Institute, LLCPhoenix, United States
- Retina Partners of Northwest Arkansas, PLLCSpringdale, United States
- Retinal Diagnostic CenterCampbell, United States
- Retina Consultants of Orange CountyFullerton, United States
- Retinal Consultants Medical GroupModesto, United States
- Northern California Retina-Vitreous AssociatesMountain View, United States
- Retinal Consultants Medical GroupSacramento, United States
- University of California San FranciscoSan Francisco, United States
- Macula Retina Vitreous Research InstituteTorrance, United States
- Bay Area Retina Associates;Study DepartmentWalnut Creek, United States
- University of Colorado - Eye Center - PPDSAurora, United States
- Retina Consultants of Southern Colorado PCColorado Springs, United States
- Retina Specialists of ColoradoDenver, United States
- Advanced Vision Research InstituteLongmont, United States
- Retina Group of New EnglandWaterford, United States
- National Ophthalmic Research InstituteFort Myers, United States
- Florida Retina InstituteJacksonville, United States
- Retina Associates of Florida;Retina Associates of FloridaTampa, United States
- Southeast Retina CenterAugusta, United States
- Georgia Retina PCMarietta, United States
- Retina Consultants of Hawaii‘Aiea, United States
- Illinois Eye and Ear InfirmaryChicago, United States
- University Retina and Macula Associates, PCOak Forest, United States
And 52 more, listed on the interactive page.
Other registry identifiers
- ISRCTN14152148
Related records
Drugs (2)
Lead sponsors (1)
Conditions (1)
- Diabetic macular edema Primary condition