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

NCT06850922 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: GR43828ISRCTN14152148
• Study Type: interventional
• Target: 546
• Locations: 3 countries
• Sites: 76

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.

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (5)

• 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

  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.

  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.

  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.

  From Baseline up to Week 56

Secondary Outcomes (7)

• Part 5: Proportion of Participants Gaining ≥ 15 Letters in BCVA From Baseline Averaged Over Weeks 52 and 56

  From Baseline up to Week 56

• Part 5: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time

  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

  From Baseline up to Week 56

• Part 5: Change From Baseline in BCVA Score Over Time

  From Baseline up to Week 56

• 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

Study Arms (5)

Part 1: Single Ascending Dose (SAD) Stage

EXPERIMENTAL

Participants received a single dose of RO7446603 at five different dose levels as IVT injection on Day 1.

Drug: RO7446603

Part 2: Multiple Dose (MD) Monotherapy Stage

EXPERIMENTAL

Participants received four different dose levels of RO7446603 (two doses at each planned dose level) as IVT injection, every 8 weeks (Q8W).

Drug: RO7446603

Part 3: MD Co-administration With Aflibercept Stage

EXPERIMENTAL

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).

Drug: RO7446603; Drug: Aflibercept

Part 4: MD Co-administration With Faricimab Stage

EXPERIMENTAL

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.

Drug: RO7446603; Drug: Faricimab

Part 5: MD Co-mixed With Faricimab Stage

EXPERIMENTAL

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.

Drug: RO7446603; Drug: Faricimab

Interventions

RO7446603 DRUG

Participants will receive RO7446603 as an IVT injection per the schedule described in the treatment arms.

Part 1: Single Ascending Dose (SAD) Stage; Part 2: Multiple Dose (MD) Monotherapy Stage; Part 3: MD Co-administration With Aflibercept Stage; Part 4: MD Co-administration With Faricimab Stage; Part 5: MD Co-mixed With Faricimab Stage

Aflibercept DRUG

Participants will receive aflibercept as an IVT injection per the schedule described in the treatment arm.

Part 3: MD Co-administration With Aflibercept Stage

Faricimab DRUG

Participants will receive faricimab as an IVT injection per the schedule described in the treatment arms.

Also known as: Vabysmo

Part 4: MD Co-administration With Faricimab Stage; Part 5: MD Co-mixed With Faricimab Stage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (76)

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, 85020-5917, United States

Location

Associated Retinal Consultants PC

Phoenix, Arizona, 85020, United States

Location

Retinal Research Institute, LLC

Phoenix, Arizona, 85053, United States

Location

Retinal Diagnostic Center

Campbell, California, 95008, United States

Location

Retina Consultants of Orange County

Fullerton, California, 92835, United States

Location

Retinal Consultants Medical Group

Modesto, California, 95356-9412, United States

Location

Northern California Retina-Vitreous Associates

Mountain View, California, 94040, United States

Location

Retinal Consultants Medical Group

Sacramento, California, 95825, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Macula Retina Vitreous Research Institute

Torrance, California, 90503-3270, United States

Location

Bay Area Retina Associates;Study Department

Walnut Creek, California, 94598, United States

Location

University of Colorado - Eye Center - PPDS

Aurora, Colorado, 80045-2517, United States

Location

Retina Consultants of Southern Colorado PC

Colorado Springs, Colorado, 80909, United States

Location

Retina Specialists of Colorado

Denver, Colorado, 80222, United States

Location

Advanced Vision Research Institute

Longmont, Colorado, 80503-6499, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385-1215, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Florida Retina Institute

Jacksonville, Florida, 32216-6347, United States

Location

Retina Associates of Florida;Retina Associates of Florida

Tampa, Florida, 33609, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909-6440, United States

Location

Georgia Retina PC

Marietta, Georgia, 30060, United States

Location

Retina Consultants of Hawaii

‘Aiea, Hawaii, 96701, United States

Location

Illinois Eye and Ear Infirmary

Chicago, Illinois, 60612, United States

Location

University Retina and Macula Associates, PC

Oak Forest, Illinois, 60452, United States

Location

Raj K. Maturi, MD PC

Indianapolis, Indiana, 46290, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Chesapeake Retina Centers - Waldorf

Waldorf, Maryland, 20602, United States

Location

Associated Retinal Consultants - Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Retina Consultants Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Long Island Vitreoretinal Consultants;Opthalmology

Hauppauge, New York, 11788, United States

Location

Retina Vitreous Surgeons of CNY PC

Liverpool, New York, 13088, United States

Location

Opthalmic Consultants of LI

Lynbrook, New York, 11563, United States

Location

Western Carolina Retinal Associate PA

Asheville, North Carolina, 28803, United States

Location

North Carolina Retina Associates

Cary, North Carolina, 27511, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Graystone Eye

Hickory, North Carolina, 28602, United States

Location

North Carolina (NC) Retina Associates - Wake Forest Office

Wake Forest, North Carolina, 27587-3803, United States

Location

Piedmont Retina Specialists

Winston-Salem, North Carolina, 27103-6970, United States

Location

Cincinnati Eye Institute

Blue Ash, Ohio, 45242-5537, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44016, United States

Location

Ohio State Eye and Ear Institute

Columbus, Ohio, 43212, United States

Location

Tulsa Retina Consultants

Tulsa, Oklahoma, 74114, United States

Location

Cascade Medical Research Institute LLC

Springfield, Oregon, 97477, United States

Location

Erie Retina Research

Erie, Pennsylvania, 16505, United States

Location

Wills Eye Hospital

Philadelphia, Pennsylvania, 19107-5109, United States

Location

Sewickely Eye Group

Sewickley, Pennsylvania, 15143, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169-2429, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Austin Clinical Research LLC

Austin, Texas, 78750, United States

Location

Retina & Vitreous of Texas

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Valley Retina Institute P.A.

McAllen, Texas, 78550-9207, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retina Consultants of Texas - San Antonio

San Antonio, Texas, 78240, United States

Location

Brown Retina Institute

San Antonio, Texas, 78251-4551, United States

Location

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

Location

Strategic Clinical Research Group, LLC

Willow Park, Texas, 76087, United States

Location

Retina Associates of Utah, PLLC;Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Piedmont Eye Center

Lynchburg, Virginia, 24502-4271, United States

Location

Wagner Kapoor Institute

Norfolk, Virginia, 23502, United States

Location

Virginia Eye Institute - Richmond - 7301 Forest Ave

Richmond, Virginia, 23230, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235-1962, United States

Location

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

Location

Beijing Tongren Hospital, Capital Medical University

Beijing, Beijing Municipality, 100730, China

Location

Shanghai General Hospital - North Campus

Shanghai, Shanghai Municipality, 200080, China

Location

Tianjin Medical University Eye Hospital

Tianjin, Tianjin Municipality, 300384, China

Location

Eye Hospital,WMU(Zhejiang Eye Hospital)

Wenzhou, Zhejiang, 325027, China

Location

Beijing Hospital

Beijing, 100730, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Emanuelli Research and Development Center LLC

Arecibo, 00612, Puerto Rico

Location

MeSH Terms

Interventions

aflibercept; faricimab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: February 28, 2025
• Study Start: June 22, 2022
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (69); CN (6); PR (1)