A Study of the Efficacy, Safety, and Pharmacokinetics (PK) of the Port Delivery System With Ranibizumab (PDS) in Chinese Participants With Neovascular Age-related Macular Degeneration (nAMD) (HUTONG)

Roche

Status and phase: Enrolling; Phase 3

Conditions: Neovascular Age-related Macular Degeneration; nAMD

Treatments: Drug: Ranibizumab (10 mg/mL); Device: PDS With Ranibizumab (100 mg/mL)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05562947

YR42983

Details and patient eligibility

About

This study will evaluate the efficacy, safety, and PK of ranibizumab 100 milligrams per milliliter (mg/mL) delivered every 24 weeks (Q24W) via the PDS implant compared with ranibizumab 0.5 milligrams (mg) delivered every 4 weeks (Q4W) as intravitreal (IVT) injection in chinese participants with nAMD.

Enrollment: 68 estimated patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Initial diagnosis of nAMD within 9 months prior to the screening visit
• Previous treatment with at least three anti-vascular endothelial growth factor (VEGF) IVT injections for nAMD per standard of care within 6 months prior to the screening visit
• Demonstrated response to prior anti-VEGF IVT treatment since diagnosis
• Availability of historical VA data prior to the first anti-VEGF treatment for nAMD up to the screening visit
• BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters
• All subtypes of nAMD lesions are permissible
• Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images

Exclusion criteria

A. Prior Ocular Treatment Study Eye

• History of vitrectomy surgery, submacular surgery, or other surgical intervention, all for AMD
• Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
• Previous treatment with corticosteroid IVT injection
• Previous intraocular device implantation (not including intraocular lens implants)
• Previous laser (any type) used for age-related macular degeneration (AMD) treatment
• Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
• Prior treatment with intravitreal treatments for geographic atrophy
• Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant

Either Eye

• Prior treatment with brolucizumab
• Prior gene therapy for nAMD or other ocular diseases
• Previous participation in any ocular disease studies of investigational drugs and/or devices, within 3 months or five elimination half-lives of the investigational therapy, whichever is longer, preceding the screening visit

B. Choroidal Neovascularization (CNV) Lesion Characteristics

Study Eye

• Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 millimeter square [mm^2]) in size at screening
• Subfoveal fibrosis or subfoveal atrophy

Either Eye • CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia

C. Concurrent Ocular Conditions Study Eye

• Retinal pigment epithelial tear
• Any concurrent intraocular condition
• Active intraocular inflammation (grade trace or above)
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the randomization visit
• History of pars plana vitrectomy surgery
• Aphakia or absence of the posterior capsule
• Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia
• Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery
• Intraocular surgery (including cataract surgery) within 3 months preceding the randomization visit
• Uncontrolled ocular hypertension or glaucoma
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant

Fellow (Non-Study) Eye

• Non-functioning fellow eye

Either Eye

• Any history of uveitis
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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68 participants in 2 patient groups

Implant Arm

Experimental group

Description:

Participants will have the implant (pre-filled intraoperatively with ranibizumab 100 mg/mL) surgically inserted on Day 1. After Day 1, participants in the implant arm will attend monthly study visits, and receive implant refill-exchanges with ranibizumab 100 mg/mL at Week 24 and Week 48. At the Week 48 study visit, participants will move to the long -term extension phase of the study and continue receiving refill-exchanges Q24W until the end of study. Participants will attend monthly visits up to Week 96 and bi-monthly visits, thereafter.

Treatment:

Device: PDS With Ranibizumab (100 mg/mL)

IVT Arm

Experimental group

Description:

Participants will receive IVT ranibizumab 0.5 mg injections starting on Day 1. Participants will receive IVT ranibizumab 0.5 mg Q4W until Week 44. At the Week 48 study visit, participants will receive the PDS implant (pre-filled intraoperatively with ranibizumab 100 mg/mL), move to the long-term extension phase of the study and receive Q24W refill exchanges until the end of study. If participants are unable to attend the Week 48 visit due to extenuating circumstances, they should return no later than the next scheduled visit (Week 52), when they will receive the PDS implant. Participants will attend monthly visits up to Week 96 and bi-monthly visits, thereafter.

Treatment:

Drug: Ranibizumab (10 mg/mL)