Clinical trial NCT06847854: A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7497372 in Participants With Diabetic Macular Edema (DME)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Diabetic Macular Edema
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 is Sequential Assignment. Part 2 is Parallel Assignment.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 28 Weeks
measure: Part 2: Number of Participants With Intraocular Inflammation (IOI) AEs as Reported by the Investigator
timeFrame: Baseline to Week 48
measure: Part 2: Number of Participants With Severe or Serious Drug-Related IOI AEs
timeFrame: Baseline to Week 48
measure: Part 2: Number of Participants With Occlusive Retinal Vasculitis AEs as Reported by the Investigator
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Part 1: Concentration of RO7497372 in Blood
timeFrame: Up to Week 28
measure: Part 1: Concentration of RO7497372 in Aqueous Humor (AH)
timeFrame: Up to Week 28
measure: Part 2: Number of Participants With AEs
timeFrame: Up to 56 weeks
measure: Part 2: Number of Participants With Persistent Treatment-induced Anti-drug Antibody (ADAs)
timeFrame: Up to 56 weeks
measure: Part 2: Concentration of RO7497372 in AH
timeFrame: Up to Week 56
measure: Part 2: Concentration of RO7497372 in Plasma
timeFrame: Up to Week 56
measure: Part 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) Score Over Time
timeFrame: From Baseline (Day 1) up to Week 56
measure: Part 2: Absolute Value of BCVA Score Over Time
timeFrame: Up to Week 56
measure: Part 2: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time
timeFrame: Up to Week 56
measure: Part 2: Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time
timeFrame: Up to Week 56
measure: Part 2: Change From Baseline in Central Subfield Thickness (CST) Over Time
timeFrame: From Baseline (Day 1) up to Week 56
measure: Part 2: Absolute Value of CST Over Time
timeFrame: Up to Week 56
measure: Part 2: Percentage of Participants With Absence of DME Over Time
timeFrame: Up to Week 56
measure: Part 2: Percentage of Participants With Absence of Intraretinal Fluid and/or Subretinal Fluid Over Time
timeFrame: Up to Week 56
measure: Part 2: Percentage of Participants With ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) Improvement From Baseline on the ETDRS DRSS Over Time
timeFrame: Up to Week 56
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Retinal Consultants of AZ, Ltd
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Modesto
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Hagerstown
country: United States
facility: Cumberland Valley Retina PC
state: Maryland
city: Grand Blanc
country: United States
facility: Retina Associates of Michigan
state: Michigan
city: Saint Louis Park
country: United States
facility: Retina Consultants Minnesota
state: Minnesota
city: Buffalo
country: United States
facility: Ross Eye Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: EyeHealth Northwest
state: Oregon
city: Erie
country: United States
facility: Erie Retinal Surgery
state: Pennsylvania
city: Austin
country: United States
facility: Austin Clinical Research LLC
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: