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.
Description
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.
Who can participate
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
Interventions
ABBV-RGX-314 Dose 1
GENETIC
ABBV-RGX-314 Dose 2
GENETIC
Aflibercept (EYLEA®)
BIOLOGICAL
Locations
181
Canada (10)
Calgary Retina Consultants /ID# 258997
Calgary , Alberta
ACTIVE_NOT_RECRUITING
Alberta Retina Consultants /ID# 265599
Edmonton , Alberta
ACTIVE_NOT_RECRUITING
Vitreous Retina Macula Specialists of Toronto /ID# 258299
Etobicoke , Ontario
ACTIVE_NOT_RECRUITING
Retina Surgical Associates /ID# 270958
New Westminster , British Columbia
ACTIVE_NOT_RECRUITING
Ottawa Hospital Research Institute /ID# 258998
Ottawa , Ontario
ACTIVE_NOT_RECRUITING
Retina Centre of Ottawa /ID# 259659
Ottawa , Ontario
ACTIVE_NOT_RECRUITING
CHU de Quebec-Universite Laval /ID# 258996
Québec , Quebec
COMPLETED
Toronto Retina Institute /ID# 265602
Toronto , Ontario
ACTIVE_NOT_RECRUITING
Sunnybrook Research Institute /ID# 270690
Toronto , Ontario
ACTIVE_NOT_RECRUITING
University of British Columbia - Eye Care Centre, Vancouver General Hospital /ID# 266014
Vancouver , British Columbia
COMPLETED
France (10)
Centre Hosp Intercommunal de Creteil /ID# 262407
Créteil , Val-de-Marne
ACTIVE_NOT_RECRUITING
CHU Dijon /ID# 262410
Dijon , Cote-d Or
ACTIVE_NOT_RECRUITING
Hôpital de la Croix Rousse - Groupement Hospitalier Nord /ID# 262409
Lyon , Auvergne-Rhône-Alpes
ACTIVE_NOT_RECRUITING
Clinique Juge /ID# 262417
Marseille , Provence-Alpes-Côte d'Azur Region
ACTIVE_NOT_RECRUITING
Clinique Honoré Cave /ID# 262225
Montauban
ACTIVE_NOT_RECRUITING
Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 262408
Nantes , Pays de la Loire Region
ACTIVE_NOT_RECRUITING
Centre Hospitalier Universitaire de Nice - Hopital Pasteur /ID# 262418
Nice , Alpes-Maritimes
ACTIVE_NOT_RECRUITING
Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 262415
Paris , Paris
ACTIVE_NOT_RECRUITING
AP-HP - Groupe Hospitalier 10e - Hopital Lariboisiere /ID# 262406
Paris
ACTIVE_NOT_RECRUITING
Chu De Toulouse - Hopital Pierre Paul Ricquet /ID# 262411
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