Clinical trial NCT06850922: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-28
Enrollment: 546
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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/exclusion criteria may apply

Primary outcomes:
measure: Parts 1-5: Percentage of Participants With Adverse Events (AEs)
timeFrame: From study start through end of study (Up to approximately 58 months)
measure: Parts 1-5: Percentage of Participants With Ocular AEs
timeFrame: From study start through end of study (Up to approximately 58 months)
measure: Part 1: Change in Best Corrected Visual Acuity (BCVA) Over Time
timeFrame: From Baseline up to Week 16
measure: Parts 2-4: Change in BCVA Over Time
timeFrame: From Baseline up to Week 28
measure: Part 5: Change From Baseline in BCVA Averaged Over Weeks 52 and 56
timeFrame: From Baseline up to Week 56
Secondary outcomes:
measure: 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
measure: 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
measure: 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
measure: Part 5: Change From Baseline in BCVA Score Over Time
timeFrame: From Baseline up to Week 56
measure: 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
measure: 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)
measure: 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)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Phoenix
country: United States
facility: Associated Retinal Consultants PC
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Modesto
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Mountain View
country: United States
facility: Northern California Retina-Vitreous Associates
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Torrance
country: United States
facility: Macula Retina Vitreous Research Institute
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado PC
state: Colorado
city: Denver
country: United States
facility: Retina Specialists of Colorado
state: Colorado
city: Longmont
country: United States
facility: Advanced Vision Research Institute
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Clearwater
country: United States
facility: Blue Ocean Clinical Research
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Jacksonville
country: United States
facility: Florida Retina Institute
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida;Retina Associates of Florida
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Lemont
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Indianapolis
country: United States
facility: Raj K. Maturi, MD PC
state: Indiana
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Hauppauge
country: United States
facility: Long Island Vitreoretinal Consultants;Opthalmology
state: New York
city: Liverpool
country: United States
facility: Retina Vitreous Surgeons of CNY PC
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associate PA
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Retina Specialists
state: North Carolina
city: Blue Ash
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State Eye and Ear Institute
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Retina Consultants
state: Oklahoma
city: Springfield
country: United States
facility: Cascade Medical Research Institute LLC
state: Oregon
city: Erie
country: United States
facility: Erie Retina Research
state: Pennsylvania
city: Sewickley
country: United States
facility: Sewickely Eye Group
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research LLC
state: Texas
city: Bellaire
country: United States
facility: Retina & Vitreous of Texas
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute P.A.
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas - San Antonio
state: Texas
city: San Antonio
country: United States
facility: Brown Retina Institute
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah, PLLC;Clinical Research
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Norfolk
country: United States
facility: Wagner Kapoor Institute
state: Virginia
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Shanghai
country: China
facility: Shanghai General Hospital - North Campus
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center LLC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: