Diabetic Macular Edema
Conditions
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.
Interventions
DRUGRO7446603
Participants will receive RO7446603 as an IVT injection per the schedule described in the treatment arms.
DRUGAflibercept
Participants will receive aflibercept as an IVT injection per the schedule described in the treatment arm.
DRUGFaricimab
Participants will receive faricimab as an IVT injection per the schedule described in the treatment arms.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 1-4: 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) | — |
| 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) | — |
Countries
China, Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed