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)

Phase 3

Recruiting

• Conditions: Neovascular Age-related Macular Degeneration; nAMD
• Interventions: Device: PDS With Ranibizumab (100 mg/mL); Drug: Ranibizumab (10 mg/mL)

• Registration Number: NCT05562947
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-15
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Study Start: 2024-06-17
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2027-06-30
• Study Completion: 2029-05-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Implant Arm	PDS With Ranibizumab (100 mg/mL)	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.
IVT Arm	Ranibizumab (10 mg/mL)	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Averaged Over Weeks 36 and 40, as Assessed Using the ETDRS Visual Acuity (VA) Chart at a Starting Distance of 4 Meters	Baseline up to Week 40

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in BCVA Score Over Time	Baseline up to Week 144
Number of Participants With Anti-drug Antibodies (ADAs)	Baseline, Weeks 4, 24, 48
Number of Participants With Treatment-emergent ADAs During the Study	Baseline, Weeks 4, 24, 48
Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 36 and 40	Baseline up to Week 40
Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 44 and 48	Baseline up to Week 48
Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged over Weeks 36 and 40	Baseline up to Week 40
Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged Over Weeks 44 and 48	Baseline up to Week 48
Proportion of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40	Baseline up to Week 40
Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48	Baseline up to Week 48
Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40	Baseline up to Week 40
Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48	Baseline up to Week 48
Change From Baseline in Center Point Thickness (CPT) at Week 36	Baseline, Week 36	CPT is retinal thickness in the center point of the fovea measured between the internal limiting membrane and the inner third of the retinal pigment epithelium layer. CPT will be measured using optical coherence tomography (OCT).
Change From Baseline in Central Subfield Thickness (CST) at Week 36	Baseline, Week 36	CST is defined as the average thickness of the central 1 millimeter (mm) circle of the ETDRS grid centered on the fovea. CST will be measured using OCT.
Change From Baseline in CPT at Week 44	Baseline, Week 44	CPT is retinal thickness in the center point of the fovea measured between the internal limiting membrane and the inner third of the retinal pigment epithelium layer. CPT will be measured using OCT.
Change From Baseline in CST at Week 44	Baseline, Week 44	CST is defined as the average thickness of the central 1 mm circle of the ETDRS grid centered on the fovea. CST will be measured using OCT.
Proportion of Participants in the Implant Arm Who do not Undergo Supplemental Treatment With IVT Ranibizumab 0.5 mg Before the First, Second, Third, Fourth, Fifth, and Sixth Fixed Refill-exchange Intervals	Baseline up to 144 weeks
Proportion of Participants in the Implant Arm Who do not Undergo a Supplemental Treatment that Requires Subsequent Additional Supplemental Treatments During the Study	Baseline up to 144 weeks
Percentage of Participants With Adverse Events (AEs)	Baseline up to 144 weeks
Percentage of Participants With Adverse Events of Special Interest (AESIs)	Baseline up to 144 weeks
Percentage of Participants With Ocular AESIs During the Post-operative Period and Follow-up Period	Post-operative period: up to 37 days after initial implantation Follow-up period: > 37 days after implantation surgery (up to 144 weeks)
Percentage of Participants Who Received PDS Affected With Adverse Device Effects (ADEs)	Baseline up to 144 weeks
Percentage of Participants Who Received PDS Affected With Anticipated Serious Adverse Device Effects (ASADEs)	Baseline up to 144 weeks
Number of Device Deficiencies	Baseline up to 144 weeks
Observed Serum Ranibizumab Concentrations at Specified Timepoints	Baseline, Weeks 4, 12, 24, 28, 36, 48
Area Under the Concentration Time Curve From 0-24 Weeks	Baseline, Weeks 4, 12, 24
Maximum Serum Concentration of Ranibizumab	Baseline, Weeks 4, 12, 24, 28, 36, 48
Minimum serum concentration of ranibizumab	Baseline, Weeks 4, 12, 24, 28, 36, 48

Trial Locations

Locations (13)

The Second Affiliated Hospital of Harbin Medical University; 🇨🇳 Harbin, China

Peking Union Medical College Hospital; 🇨🇳 Beijing City, China

Beijing Hospital; 🇨🇳 Beijing, China

Beijing Tongren Hospital; 🇨🇳 Beijing, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, China

Zhongshan Ophthalmic Center, Sun Yat-sen University; 🇨🇳 Guangzhou City, China

Qingdao Eye Hospital of Shandong First Medical University; 🇨🇳 Qingdao City, China

Shanghai First People's Hospital; 🇨🇳 Shanghai, China

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China

Shanxi Eye Hospital; 🇨🇳 Taiyuan City, China

Tianjin Medical University Eye Hospital; 🇨🇳 Tianjin City, China

Eye Hospital, Wenzhou Medical University; 🇨🇳 Wenzhou City, China

Xi'an People's Hospital (Xi'an Fourth Hospital); 🇨🇳 XI An, China