A Randomized, Controlled, Partially Masked, Phase 3b Study to Assess the Injection Burden, Efficacy, Safety, and Long-Term Preservation of Visual Acuity of Surabgene Lomparvovec (ABBV-RGX-314) in a Real-World Context in Subjects with Neovascular Age-Related Macular Degeneration (nAMD)

The primary objective of this study is to evaluate the anti-VEGF injection burden and long-term efficacy following subretinal administration of surabgene lomparvovec compared to pro re nata (PRN) intravitreal ranibizumab administered according to protocol-specified criteria during Year 1, and subsequently compared to a PRN intravitreal ranibizumab schedule that reflects real-world clinical practice after Year 1. This objective addresses a clinically significant concern in the management of neovascular age-related macular degeneration, as reducing the frequency of intravitreal injections while maintaining therapeutic efficacy and preserving visual acuity represents an important treatment goal for patients requiring chronic anti-VEGF therapy. The assessment of injection burden is particularly relevant given the substantial treatment burden associated with repeated intravitreal injections in current standard care for neovascular age-related macular degeneration.

This clinical trial enrolled a total of **289 participants** diagnosed with **neovascular age-related macular degeneration**, specifically **choroidal neovascularization** secondary to **AMD**. The study population included both **male** and **female** subjects, comprising **adults** and **elderly** individuals. Participants were selected based on specific ophthalmic criteria, including having undergone **cataract surgery** at least 12 weeks prior to screening in the study eye and being **pseudophakic**. Eligible subjects were required to have received at least 2 **intravitreal anti-VEGF injections** in the 6 months preceding screening and demonstrated responsiveness to this treatment as determined by the investigator. No vulnerable populations were included in this trial. The sponsor did not provide information regarding lifestyle considerations such as diet, physical activity, or habits.

This is a randomized, controlled, partially masked, Phase 3b/4 clinical trial evaluating the injection burden, efficacy, safety, and long-term preservation of visual acuity of surabgene lomparvovec (ABBV-RGX-314) in participants with neovascular age-related macular degeneration (nAMD). The study compares subretinal administration of surabgene lomparvovec, an adeno-associated viral vector serotype 8 encoding a human antigen-binding fragment against vascular endothelial growth factor, with intravitreal administration of ranibizumab as a comparator. The trial employs a pro re nata (PRN) dosing regimen for ranibizumab according to protocol-specified criteria during Year 1, followed by a PRN schedule that mimics real-world clinical practice after Year 1. The primary objective is to evaluate anti-VEGF injection burden and long-term efficacy after subretinal surabgene lomparvovec administration compared to the ranibizumab treatment arms.

The trial is designed as a non-low intervention study with an estimated recruitment start date of March 30, 2026, and an estimated end date of April 6, 2033, indicating a total trial duration of approximately 7 years. The maximum treatment period for both investigational medicinal products is 60 months. Surabgene lomparvovec is administered as a suspension for injection via subretinal use, delivered using specialized devices including a DORC Extendible 41G subretinal injection needle and MedOne 3277 Microdose Injection Kit. Ranibizumab is administered as a solution for injection in pre-filled syringe via intravitreal use. The study involves gene therapy as surabgene lomparvovec is classified as an advanced therapy medicinal product.

Eligible participants must be pseudophakic in the study eye (at least 12 weeks post cataract surgery at screening), have a diagnosis of choroidal neovascularization (CNV) secondary to AMD in the study eye, and must have received at least 2 intravitreal anti-VEGF injections in the past 6 months prior to screening with demonstrated responsiveness as determined by the investigator. The primary endpoint is the annualized intravitreal anti-VEGF injection rate from Week 6 through Week 54. Secondary endpoints include change from baseline in best-corrected visual acuity (BCVA) at Year 3, annualized intravitreal anti-VEGF injection rate from Week 6 through Year 3, incidence and severity of ocular adverse events in the study eye and contralateral eye, and change from baseline in area of macular atrophy based on fundus autofluorescence (FAF) at assessed time points in the study eye.

The study involves multiple visits throughout the trial period, beginning with Screening Visit 1 at Week –6. Following screening and baseline assessments, participants receive their assigned treatment with follow-up visits scheduled at regular intervals to monitor efficacy and safety parameters. The trial continues through Year 3 and beyond, with long-term follow-up extending to the study completion date. Participant involvement is expected to span several years, with the duration dependent on treatment assignment and individual response. Conditions that may lead to early termination from the study include occurrence of significant adverse events, failure to meet protocol-specified criteria, withdrawal of consent, or investigator decision based on safety or efficacy concerns. The study design incorporates assessment of both short-term and long-term outcomes to comprehensively evaluate the therapeutic potential of surabgene lomparvovec in reducing treatment burden while maintaining or improving visual function in patients with neovascular age-related macular degeneration.

The experimental treatment in this clinical trial consists of Surabgene Lomparvovec (ABBV-RGX-314), an adeno-associated viral vector serotype 8 encoding a human antigen-binding fragment against vascular endothelial growth factor. This investigational medicinal product is classified as an advanced therapy medicinal product and is formulated as a suspension for injection. The active substance is administered via subretinal use, with the dosage measured in microliters. The maximum treatment period is specified as 60 months. The administration of Surabgene Lomparvovec requires specialized medical devices including the DORC Extendible 41G subretinal injection needle (23 gauge / 0.6 mm, Article No: 1270.EXT), West 13mm Vial Adapter, and MedOne 3277 Microdose Injection Kit (Syringe & VFI Tubing). The subretinal injection needle enables controlled subretinal injection of the investigational product. The vial adapter is a single-use, sterile, non-invasive medical device intended for the transfer and mixing of drugs contained in vials, with puncturing of the elastomeric closure achieved by means of an integral plastic spike. The MedOne MicroDose Injection Kit adapts the viscous fluid injection set from the vitrectomy machine to use a 1 mL syringe, allowing full surgeon control of subretinal injection via console foot pedal with minimal fluid loss.

The comparator treatment utilized in this study is Lucentis 10 mg/ml solution for injection in pre-filled syringe, which contains ranibizumab as the active substance. Ranibizumab is a protein classified under the ATC code S01LA04. This authorized medicinal product, manufactured by Novartis Europharm Limited, is presented as a solution for injection and is administered via intravitreal use. The marketing authorization number is EU/1/06/374/003. The comparator is administered according to a pro re nata (PRN) schedule based on protocol-specified criteria during Year 1, and subsequently according to a PRN intravitreal ranibizumab schedule that mimics the real-world clinic setting after Year 1. The maximum treatment period for the comparator is also specified as 60 months. The dosage is measured in milligrams.

Efficacy will be assessed through the evaluation of anti-VEGF injection burden and visual acuity outcomes. The primary endpoint is the annualized intravitreal anti-VEGF injection rate from Week 6 through Week 54. Secondary endpoints include the change from baseline in best-corrected visual acuity (BCVA) at Year 3, the annualized intravitreal anti-VEGF injection rate from Week 6 through Year 3, and the change from baseline in area of macular atrophy based on fundus autofluorescence (FAF) at assessed time points in the study eye. Additional secondary endpoints comprise the incidence and severity of ocular adverse events in both the study eye and contralateral eye. The assessment of efficacy will compare outcomes following subretinal surabgene lomparvovec administration to those achieved with pro re nata (PRN) intravitreal ranibizumab administered according to protocol-specified criteria during Year 1, and subsequently to a PRN intravitreal ranibizumab schedule that reflects real-world clinical practice after Year 1.