A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7497372 in Participants With Diabetic Macular Edema (DME) (Pregonda)

A Phase I, Multipart, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7497372 Following Intravitreal Administration in Participants With Diabetic Macular Edema (Part 1 Non-Randomized, Open-Label, Multiple Ascending Dose; Part 2 Randomized, Double-Masked)

This study will assess the safety and tolerability of RO7497372 in participants with DME. The study consists of 2 parts. Part 1 will test multiple-ascending doses of RO7497372 after unilateral intravitreal (IVT) administration in participants with DME. The main purpose of Part 1 is to provide data for RO7497372 safety and tolerability, as well as to characterize the ocular and systemic pharmacokinetics (PK), systemic anti-drug antibodies (ADA), and duration of target engagement, i.e., the pharmacodynamics (PD) in aqueous humor (AH) and blood. Part 2 will evaluate the safety, tolerability, PK, and PD of two dose strengths of RO7497372 (low dose and high dose), identified as safe and tolerated in Part 1.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: RO7497372

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research and Development Center
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Peoria, Arizona, United States, 85381
      • Retinal Consultants of AZ, Ltd
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Retina Research
  • California
    • Glendale, California, United States, 91204
      • Global Research Management
    • Modesto, California, United States, 95356
      • Retinal Consultants Medical Group
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Florida
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • South Miami, Florida, United States, 33143
      • Medeye Associates
    • Stuart, Florida, United States, 34994
      • East Florida Eye Institute
    • Wesley Chapel, Florida, United States, 33544
      • Retina Specialists of Tampa
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macula Disease
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina PC
  • Michigan
    • Grand Blanc, Michigan, United States, 48439-8301
      • Retina Associates of Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Foundation for Vision Research
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Retina Consultants Minnesota
  • Mississippi
    • Madison, Mississippi, United States, 39202
      • Mississippi Retina Associates
  • Missouri
    • St Louis, Missouri, United States, 63128
      • The Retina Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New York
    • Buffalo, New York, United States, 14209-2102
      • Ross Eye Institute
    • New York, New York, United States, 10075
      • Retina Associates of NY
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research LLC
    • Portland, Oregon, United States, 97225
      • EyeHealth Northwest
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retinal Surgery
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Carolina Eyecare Physicians
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
  • Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research LLC
    • Schertz, Texas, United States, 78154
      • Brown Retina Institute
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas
  • Utah
    • West Jordan, Utah, United States, 84088
      • Salt Lake Retina
  • Virginia
    • Fairfax, Virginia, United States, 20815
      • Retina Group of Washington
    • Falls Church, Virginia, United States, 78503
      • Emerson Clinical Research Institute
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
    • Norfolk, Virginia, United States, 23502
      • Wagner Kapoor Institute
  • Washington
    • Spokane, Washington, United States, 99204-2509
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of diabetes mellitus (type 1 or type 2), as defined by the world health organization (WHO) and/or American Diabetes Association
• Participant consents to AH collection
• Collection of > 90 microlitres (µL) AH (at each visit required per schedule of activities [SoA]) if deemed feasible and safe by the Investigator.
• Macular thickening secondary to DME involving the center of the fovea with CST >= 325 µm at screening
• Decreased BCVA primarily due to DME with ETDRS score of 78 to 19 letters (both inclusive) at screening
• Adequately clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images
• Diagnosis of non-proliferative DR
• Treatment-naive and Pre-treated participants after washout

Exclusion Criteria:

• Any major illness or major surgical procedure ≤ 4 weeks before Day 1
• Any febrile illness and associated sequelae ≤ 1 week prior to Day 1
• Active cancer ≤ 1 year prior to Day 1
• Cerebral vascular accident (including stroke and transient ischemic attack) or myocardial infarction ≤ 24 weeks prior to Day 1
• HbA1c ≥ 12% at screening
• Any panretinal photocoagulation or macular laser photocoagulation treatment prior to Day 1
• History of vitreoretinal surgery/pars plana vitrectomy
• Any cataract surgery within 12 weeks prior to Day 1 or any planned surgery during the study
• History of any glaucoma surgery including laser glaucoma procedures
• Uncontrolled glaucoma
• Any active intra- or periocular infection on Day 1
• Any active or history of Intraocular inflammation
• Intravitreal treatment with an anti-IL-6 (e.g., vamikibart) or anti-IL-6 receptor treatment at any time
• Any proliferative DR

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Multiple Ascending Dose; Participants will receive multiple ascending doses of RO7497372, 3 times every 4 weeks (Q4W) as an IVT injection up to Week 8 in the study eye.	Drug: RO7497372; RO7497372 will be administered as IVT injection as per the schedule specified in the arms.
Experimental: Part 2: RO7497372 Low Dose; Participants will receive 6 doses of RO7497372, low dose, Q4W followed by 3 doses, every eight weeks (Q8W) as an IVT injection up to Week 44 in the study eye.	Drug: RO7497372; RO7497372 will be administered as IVT injection as per the schedule specified in the arms.
Experimental: Part 2: RO7497372 High Dose; Participants will receive 6 doses of RO7497372, high dose, Q4W followed by 3 doses, Q8W as an IVT injection up to Week 44 in the study eye. Treatment in this arm has been discontinued due to the Sponsor's decision.	Drug: RO7497372; RO7497372 will be administered as IVT injection as per the schedule specified in the arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Adverse Events (AEs)		Up to 28 Weeks
Part 2: Number of Participants With Intraocular Inflammation (IOI) AEs as Reported by the Investigator		Baseline to Week 48
Part 2: Number of Participants With Severe or Serious Drug-Related IOI AEs	Number of participants with severe or serious drug-related IOI AEs severity will be determined according to the DAIDS toxicity grading scale as reported by the Investigator.	Baseline to Week 48
Part 2: Number of Participants With Occlusive Retinal Vasculitis AEs as Reported by the Investigator		Baseline to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Concentration of RO7497372 in Blood		Up to Week 28
Part 1: Concentration of RO7497372 in Aqueous Humor (AH)		Up to Week 28
Part 2: Number of Participants With AEs	Number of participants with AEs severity determined according to the DAIDS toxicity grading scale.	Up to 56 weeks
Part 2: Number of Participants With Persistent Treatment-induced Anti-drug Antibody (ADAs)		Up to 56 weeks
Part 2: Concentration of RO7497372 in AH		Up to Week 56
Part 2: Concentration of RO7497372 in Plasma		Up to Week 56
Part 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) Score 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 indicates improvement in VA.	From Baseline (Day 1) up to Week 56
Part 2: Absolute Value of BCVA Score 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 indicates improvement in VA.	Up to Week 56
Part 2: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline 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 indicates improvement in VA.	Up to Week 56
Part 2: Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline 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 indicates improvement in VA.	Up to Week 56
Part 2: Change From Baseline in Central Subfield Thickness (CST) Over Time	CST is defined as the average thickness of the central 1-mm circle of the ETDRS grid centered to the fovea measured between the internal limiting membrane and the Bruch's membrane. CST will be determined by CRC evaluation of SD-OCT images.	From Baseline (Day 1) up to Week 56
Part 2: Absolute Value of CST Over Time	CST is defined as the average thickness of the central 1-mm circle of the ETDRS grid centered to the fovea measured between the internal limiting membrane and the Bruch's membrane. CST will be determined by CRC evaluation of SD-OCT images.	Up to Week 56
Part 2: Percentage of Participants With Absence of DME Over Time	Absence of DME is defined as CST < 325 micrometre (μm) by spectral domain optical coherence tomography (SD-OCT).	Up to Week 56
Part 2: Percentage of Participants With Absence of Intraretinal Fluid and/or Subretinal Fluid Over Time	Presence of intraretinal and subretinal fluid will be determined by CRC evaluation of SD -OCT images.	Up to Week 56
Part 2: Percentage of Participants With ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) Improvement From Baseline on the ETDRS DRSS Over Time	The DRSS will be graded according to ETDRS grading schedules from report 18 JOVS, February 1998, Vol. 39, No. 2. ETDRS DRSS is 13 step scale which measures severity of diabetic retinopathy (DR). The DRSS scores vary from 10 (DR absent) to 90 (ungradable proliferative diabetic retinopathy(PDR)). Higher levels indicate higher severity.	Up to Week 56

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2022
• Primary Completion (Estimated): November 16, 2026
• Study Completion (Estimated): January 12, 2027

Study Registration Dates

• First Submitted: February 21, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Edema; Macular Edema
• Other Study ID Numbers: BP44175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No