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

AbbVie

Status and phase: Enrolling; Phase 3

Conditions: Wet Age-related Macular Degeneration; WetAMD; AMD; wAMD; CNV; nAMD

Treatments: Genetic: RGX-314 Dose 2; Biological: Aflibercept (EYLEA®); Genetic: RGX-314 Dose 1

Study type: Interventional

Funder types: Industry

Identifiers

NCT05407636

RGX-314-3101

Details and patient eligibility

About

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-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. RGX-314 is being developed as a potential one-time treatment for wet AMD.

Full description

This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of 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 RGX-314 relative to aflibercept. Approximately 465 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

Enrollment: 465 estimated patients

Sex: All

Ages: 50 to 89 years old

Volunteers: No Healthy Volunteers

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 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

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. Active or history of retinal detachment or current retinal tear in the study eye
5. Advanced glaucoma or history of secondary glaucoma in the study eye
6. Myocardial infarction, cerebrovascular accident, or transient ischemic attach within the past 6 months.
7. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1
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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

465 participants in 3 patient groups

RGX-314 Dose 1

Experimental group

Description:

RGX-314 Dose 1 administered via subretinal delivery one time.

Treatment:

Genetic: RGX-314 Dose 1

RGX-314 Dose 2

Experimental group

Description:

RGX-314 Dose 2 administered via subretinal delivery one time.

Treatment:

Genetic: RGX-314 Dose 2

Control Arm

Active Comparator group

Description:

Aflibercept administered via intravitreal injection approximately every 8 weeks

Treatment:

Biological: Aflibercept (EYLEA®)