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 (THAMES)

Genentech

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Diabetic Macular Edema

Treatments: Drug: Faricimab; Drug: Aflibercept; Drug: RO7446603

Study type: Interventional

Funder types: Industry

Identifiers

NCT06850922

GR43828

ISRCTN14152148 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 546 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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
• Active or history of uveitis, vitritis (grade trace or above), and/or scleritis in either eye Other protocol-specified inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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546 participants in 5 patient groups

Part 1: Single Ascending Dose (SAD) Stage

Experimental group

Description:

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

Treatment:

Drug: RO7446603

Part 2: Multiple Dose (MD) Monotherapy Stage

Experimental group

Description:

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

Treatment:

Drug: RO7446603

Part 3: MD Co-administration With Aflibercept Stage

Experimental group

Description:

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).

Treatment:

Drug: RO7446603

Drug: Aflibercept

Part 4: MD Co-administration With Faricimab Stage

Experimental group

Description:

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.

Treatment:

Drug: RO7446603

Drug: Faricimab

Part 5: MD Co-mixed With Faricimab Stage

Experimental group

Description:

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.

Treatment:

Drug: RO7446603

Drug: Faricimab