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

Phase 1Active Not RecruitingNCT06847854

Genentech, Inc.151 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

151

Conditions

Diabetic Macular Edema

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (38)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, United States

Retinal Consultants of AZ, Ltd

Peoria, Arizona, United States

Associated Retina Consultants

Phoenix, Arizona, United States

Arkansas Retina Research

Little Rock, Arkansas, United States

Global Research Management

Glendale, California, United States

Outcomes

Primary Outcomes

Part 1: Number of Participants With Adverse Events (AEs)

Time frame: Up to 28 Weeks

Part 2: Number of Participants With Intraocular Inflammation (IOI) AEs as Reported by the Investigator

Time frame: 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.

Time frame: Baseline to Week 48

Part 2: Number of Participants With Occlusive Retinal Vasculitis AEs as Reported by the Investigator

Time frame: Baseline to Week 48

Secondary Outcomes

Part 1: Concentration of RO7497372 in Blood

Time frame: Up to Week 28

Part 1: Concentration of RO7497372 in Aqueous Humor (AH)

Time frame: 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.

Time frame: Up to 56 weeks

Part 2: Number of Participants With Persistent Treatment-induced Anti-drug Antibody (ADAs)

Time frame: Up to 56 weeks

Part 2: Concentration of RO7497372 in AH

Time frame: Up to Week 56

Part 2: Concentration of RO7497372 in Plasma

Time frame: 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.

Time frame: 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.

Time frame: Up to Week 56

Part 2: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time

Time frame: 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

Time frame: 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.

Time frame: From Baseline (Day 1) up to Week 56

Part 2: Absolute Value of CST Over Time

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: Up to Week 56