A Study Of The Effectiveness And Safety Of A 36-Week Refill Regimen For The Port Delivery System With Ranibizumab Vs Aflibercept Treat & Extend In Subjects With Neovascular Age-Related Macular Degeneration

NCT05126966 | Withdrawn Phase 3 DMC FDA Drug FDA Device

• 2 other identifiers: MR424102021-003226-71
• Study Type: interventional
• Target: N/A
• Locations: 7 countries
• Sites: 10

Brief Summary

This study will evaluate the effectiveness and safety of a 36-week refill regimen for the Port Delivery System with ranibizumab 100 mg/mL (PDS Q36W) compared with intravitreal injections of aflibercept (2 mg) administered per treat-and-extend (aflibercept T\&E) in subjects with neovascular (wet) age-related macular degeneration (nAMD).

Conditions

Neovascular Age-Related Macular Degeneration

Keywords

Wet AMD; neovascular AMD; exudative AMD

Outcome Measures

Primary Outcomes (2)

• Change from baseline in BCVA score at week 80 as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters

  \*Depending on the T\&E schedule, some subjects in the comparator arm will have a visit at Week 76 and some at Week 78. All subjects in both arms will have a Week 80 visit

  From baseline up to 80 weeks

• Treatment burden as assessed by the treatment frequency up to Week 80

  Treatments include injections and refills.

  From baseline up to 80 weeks

Secondary Outcomes (11)

• Proportion of subjects with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better averaged over Weeks 76 (or 78*) and 80

  Baseline, Week 76, Week 78, Week 80

• Proportion of subjects with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse averaged over Weeks 76 (or 78*) and 80

  Baseline, Week 76, Week 78, Week 80

• Proportion of subjects who lose < 15, < 10, or < 5 letters in BCVA score from baseline averaged over Weeks 76 (or 78*) and 80

  Baseline, Week 76, Week 78, Week 80

• Change from baseline in center point thickness (CPT) at Week 80

  Baseline, Week 80

• Change from baseline in center subfield thickness (CST), defined as the average thickness of the central 1 mm circle of the ETDRS grid centered on the fovea measured between the internal limiting membrane and the Bruch's membrane, on SD-OCT at Week 80

  Baseline, Week 80

Study Arms (2)

Ranibizumab

EXPERIMENTAL

Subjects will have the implant (filled intra-operatively prior to implantation with approximately 20 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. Subjects will have their implant refilled with ranibizumab at weeks 36 and 72.

Drug: Ranibizumab; Device: Port Delivery System with ranibizumab (PDS)

Aflibercept

ACTIVE COMPARATOR

Subjects will receive intravitreal injections of aflibercept (2mg) administered in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment.

Drug: Aflibercept

Interventions

Ranibizumab DRUG

Ranibizumab will be administered at a dose of 100 mg/mL delivered via the PDS.

Ranibizumab

Aflibercept DRUG

Aflibercept will be administered at a dose of 2 mg in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment

Aflibercept

Port Delivery System with ranibizumab (PDS) DEVICE

PDS is an investigation intraocular drug delivery device designed to continuously deliver anti-VEGF therapy.

Ranibizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age ≥ 50 years, at time of signing Informed Consent Form
• Ability and willingness to undertake all scheduled visits and assessments
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
• Initial diagnosis of nAMD within 9 months prior to the screening visit
• Previous treatment with at least three anti-VEGF intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
• Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis
• Availability of historical visual acuity data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
• Availability of historical SD-OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
• BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and randomization visits
• With any subtype of nAMD lesions (i.e., type I, type II, type III, or mixed forms per OCT classification, including polypoidal choroidal vasculopathy and retinal angiomatous proliferation)
• Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of fundus photography (FP), FA, fundus autofluorescence (FAF) image, and SD-OCT images

You may not qualify if:

• Prior Ocular Treatment - Study Eye
• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
• Prior pars plana vitrectomy surgery
• Prior treatment with Visudyne® (verteporfin for injection), external-beam radiation therapy, or transpupillary thermotherapy
• Previous treatment with corticosteroid intravitreal injection
• Previous intraocular device implantation (not including intraocular lens implants)
• Previous intraocular surgery (including cataract surgery) within 3 months of randomization
• Previous laser (any type) used for AMD or diabetic retinopathy treatment
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant
• History of conjunctival surgery in the superotemporal quadrant (including pterygium surgery)
• Prior Ocular Treatment Either Eye:

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

Oftalmos

Capital Federal, C1120AAN, Argentina

Location

Rigshospitalet Glostrup; Afdeling for Øjensygdomme

Glostrup Municipality, 2600, Denmark

Location

Sjællands Universitetshospital, Roskilde; Øjenafdelingen

Roskilde, 4000, Denmark

Location

University Hospital of Larissa; Department of Ophthalmology

Larissa, 412 21, Greece

Location

Queen Mary Hospital; Department of Ophthalmology

Hong Kong, Hong Kong

Location

Hong Kong Eye Hospital; CUHK Eye Centre

Mong Kok, Hong Kong

Location

Hospital de Sao Joao; Servico de Oftalmologia

Porto, 4200-319, Portugal

Location

Hospital de la Arruzafa. Servicio de Oftalmologia

Córdoba, 14012, Spain

Location

King Chulalongkorn Memorial Hospital; Ophthalmology Department

Bangkok, 10330, Thailand

Location

Maharaj Nakorn ChiangMai Hospital; Ophthalmology Department

Chiang Mai, 50200, Thailand

Location

MeSH Terms

Interventions

Ranibizumab; aflibercept

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 19, 2021
• Study Start: December 29, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 30, 2026
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

TH (2); DK (2); GR (1); PT (1); ES (1); AR (1); HK (2)