Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD

Phase 3RecruitingNCT05407636

AbbVie714 enrolled

Overview

ABBV-RGX-314 (also known as RGX-314 and surabgene lomparvovec (sura-vec)) is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-vascular endothelial growth factor (VEGF) therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. ABBV-RGX-314 is being developed as a potential one-time treatment for wet AMD.

This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to aflibercept. Approximately 714 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms. A bilateral treatment substudy conducted at US sites is an open-label, partially randomized, parallel arm study to evaluate the safety and efficacy of subretinal ABBV-RGX-314 administered bilaterally in participants who have bilateral nAMD. Previously treated crossover participants from the control arm of the main study who crossed over and received ABBV-RGX-314 in the study eye will receive the same ABBV-RGX-314 dose in the contralateral eye (ie, same dose as in the study eye), while newcomers (participants who have not been randomized in an ABBV-RGX-314 study) and untreated crossover participants (ongoing control participants in the main study who have completed Week 54 but have not crossed over to receive ABBV-RGX-314 in the main study) will be randomized in a 2:1 ratio to receive ABBV-RGX-314 Dose 1 or ABBV-RGX-314 Dose 2 in both eyes. Up to 15 participants who qualify for the substudy will be enrolled and followed for a minimum of 50 weeks.

Study Type

INTERVENTIONAL

Eligibility

Sex: ALLMin age: 50 YearsMax age: 89 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 50 years and ≤ 89 years 2. An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye 3. Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in the study eye previously treated with anti-VEGF 4. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye 5. Willing and able to provide written, signed informed consent for this study 6. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry Inclusion Criteria (Bilateral Treatment Substudy)\*: 1. An ETDRS BCVA letter score between ≤ 83 and ≥ 40 in both eyes 2. Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in both eyes 3. Must be pseudophakic (at least 12 weeks postcataract surgery) in both eyes 4. Willing and able to provide written, signed informed consent for this study 5. Newcomers must have active disease in the study eye; crossover participants must have active disease in the eye not treated in the main study Exclusion Criteria: 1. CNV or macular edema in the study eye secondary to any causes other than AMD 2. Subfoveal fibrosis or atrophy in the study eye 3. Any condition in the investigator's opinion that could limit VA improvement in the study eye 4. Advanced glaucoma or history of secondary glaucoma in the study eye 5. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 6. History of intraocular surgery in the study eye within 12 weeks prior to randomization 7. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -6 8. Prior treatment with gene therapy Exclusion Criteria (Bilateral Treatment Substudy)\*: 1. CNV or macular edema in either eye secondary to any causes other than AMD 2. Subfoveal fibrosis or atrophy in either eye 3. Any condition in the investigator's opinion that could limit VA improvement in either eye 4. Advanced glaucoma or history of secondary glaucoma in either eye 5. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 6. History of intraocular surgery in either eye within 12 weeks prior to randomization 7. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -6. 8. Prior treatment with gene therapy (\*) For previously treated crossover participants, criteria apply to the eye not treated in the main study only. Note: Other inclusion/exclusion criteria apply

Locations (181)

Barnet Dulaney Eye Center-Phoenix /ID# 256340

Phoenix, Arizona, United States

RECRUITING

Retinal Research Institute /ID# 256238

Phoenix, Arizona, United States

RECRUITING

Retina Macula Institute of Arizona /ID# 271026

Scottsdale, Arizona, United States

RECRUITING

California Retina Consultants - Bakersfield /ID# 256240

Bakersfield, California, United States

Outcomes

Primary Outcomes

Mean change from baseline in Best Corrected Visual Acuity (BCVA)

To evaluate the noninferiority of ABBV-RGX-314 relative to aflibercept in mean change from Baseline BCVA at Week 54

Time frame: At Week 54

Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs

AEs and SAEs through Week 50

Time frame: Week 50

Secondary Outcomes

Incidences of ocular and overall AEs

To evaluate the safety and tolerability of ABBV-RGX-314 through Week 54

Time frame: Through Week 54

Proportion of participants with improved BCVA

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

Time frame: Week 54

Proportion of participants with worsened BCVA

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

Time frame: Week 54

Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

Time frame: Week 54

Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injection (ABBV-RGX- 314 randomized participants)

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

Time frame: Week 54

Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314)

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

Time frame: Week 54 to Week 108

Mean change in central retinal thickness (CRT) as measured by SD-OCT

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CRT as measured by SD-OCT

Time frame: Through Week 108

Mean change in central point thickness (CPT) as measured by SD-OCT

To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CPT as measured by SD-OCT

Time frame: Through Week 108

Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)