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

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Diabetic Macular Edema

Treatments: Drug: RO7497372

Study type: Interventional

Funder types: Industry

Identifiers

NCT06847854

BP44175

Details and patient eligibility

About

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.

Enrollment: 176 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

---

176 participants in 3 patient groups

Part 1: Multiple Ascending Dose

Experimental group

Description:

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.

Treatment:

Drug: RO7497372

Part 2: RO7497372 Low Dose

Experimental group

Description:

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.

Treatment:

Drug: RO7497372

Part 2: RO7497372 High Dose

Experimental group

Description:

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:

Drug: RO7497372