Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD
Purpose
ABBV-RGX-314 (also known as RGX-314) 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.
Conditions
- AMD
- nAMD
- Wet Age-related Macular Degeneration
- wAMD
- WetAMD
- CNV
Eligibility
- Eligible Ages
- Between 50 Years and 89 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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. Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye 5. Advanced glaucoma or history of secondary glaucoma in the study eye 6. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 7. History of intraocular surgery in the study eye within 12 weeks prior to randomization 8. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1 9. 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. Active or history of retinal detachment, or current retinal tear that cannot be treated in either eye 5. Advanced glaucoma or history of secondary glaucoma in either eye 6. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 7. History of intraocular surgery in either eye within 12 weeks prior to randomization 8. History of intravitreal therapy in either eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening 9. 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 2 ABBV-RGX-314 treatment arms, 1 control arm (aflibercept)
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- ABBV-RGX-314 administration is performed as an outpatient surgical procedure in an operating room, while the active control, aflibercept, is administered via intravitreal injection in an office setting. This study will be partially masked which will include masking of key study assessors and study drug dose.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental ABBV-RGX-314 Dose 1 |
ABBV-RGX-314 Dose 1 administered via subretinal delivery one time. |
|
|
Experimental ABBV-RGX-314 Dose 2 |
ABBV-RGX-314 Dose 2 administered via subretinal delivery one time. |
|
|
Active Comparator Control Arm |
Aflibercept administered via intravitreal injection approximately every 8 weeks |
|
Recruiting Locations
Nashville 4644585, Tennessee 4662168 37232-0011
More Details
- Status
- Recruiting
- Sponsor
- AbbVie
Detailed 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 660 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), and 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.