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)

Official title

A Phase III, Multicenter, Randomized, Visual Assessor-masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Chinese Patients With Neovascular Age-related Macular Degeneration

Overview

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.

Interventions

• Device PDS With Ranibizumab (100 mg/mL)
  Participants randomized to the implant arm will have the implant (filled prior to implantation with approximately 20 microliters (μL) of the 100 mg/mL formulation of ranibizumab \[approximately 2 mg dose of ranibizumab\]) surgically inserted in the study eye at the Day 1 visit following their randomization visit, or at Week 48 visit for participants randomized to the IVT arm. After the initial fill of the implant with ranibizumab, participants will receive implant refill-exchanges at fixed 24-we
• Drug Ranibizumab (10 mg/mL)
  Participants in the IVT arm will receive their first IVT injection of 50 μL of the 10 mg/mL ranibizumab (0.5 mg dose) at the Day 1 visit, which will occur at the conclusion of the randomization visit. Afterwards, participants will receive IVT ranibizumab injections of 50 μL of the 10 mg/mL formulation Q4W at each scheduled study visit until Week 44 and bi-monthly visits thereafter, followed by visits every two months until study completion.

Primary outcome measures

• 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 [Time frame: Baseline up to Week 40]

Secondary outcome measures (12)

• Change From Baseline in BCVA Score Over Time [Time frame: Baseline up to Week 144]
• Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 36 and 40 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Baseline up to Week 48]
• Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40 [Time frame: Baseline up to Week 40]
• Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48 [Time frame: 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 [Time frame: 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 [Time frame: Baseline up to Week 48]
• Change From Baseline in Center Point Thickness (CPT) at Week 36 [Time frame: Baseline and Week 36]
• Change From Baseline in Central Subfield Thickness (CST) at Week 36 [Time frame: Baseline and Week 36]
• Change From Baseline in CPT at Week 44 [Time frame: Baseline and Week 44]

Eligibility criteria

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 (SOC) 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 or corticosteroid implants
• 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 IVT 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 16 centers

• Peking Union Medical College Hospital — Beijing
• Beijing Hospital — Beijing
• Beijing Tongren Hospital — Beijing
• West China Hospital, Sichuan University — Chengdu
• Sichuan Provincial People's Hospital — Chengdu
• Zhongshan Ophthalmic Center, Sun Yat-sen University — Guangzhou
• The Second Affiliated Hospital of Harbin Medical University — Harbin
• Qingdao Eye Hospital of Shandong First Medical University — Qingdao
• … and 8 more centers

Identifiers

NCT: NCT05562947 · YR42983

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗