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

Sponsor

REGENXBIO, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05407636

Collaborator

(none)

465

Enrollment

Locations

Arms

35.1

Anticipated Duration (Months)

27.4

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
AMD nAMD Wet Age-related Macular Degeneration wAMD WetAMD CNV	Genetic: RGX-314 Dose 1 Genetic: RGX-314 Dose 2 Biological: Aflibercept (EYLEA®)	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

465 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 RGX-314 treatment arms, 1 control arm (aflibercept)2 RGX-314 treatment arms, 1 control arm (aflibercept)

Masking:

Single (Participant)

Masking Description:

Care Provider, Investigator, Outcomes Assessor

Primary Purpose:

Treatment

Official Title:

A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD

Actual Study Start Date :

Dec 28, 2021

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RGX-314 Dose 1 RGX-314 Dose 1 administered via subretinal delivery one time.	Genetic: RGX-314 Dose 1 AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
Experimental: RGX-314 Dose 2 RGX-314 Dose 2 administered via subretinal delivery one time.	Genetic: RGX-314 Dose 2 AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
Active Comparator: Control Arm Aflibercept administered via intravitreal injection approximately every 8 weeks	Biological: Aflibercept (EYLEA®) 2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections Other Names: • Eylea (anti-VEGF agent)

Arm

Intervention/Treatment

Experimental: RGX-314 Dose 1

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

Genetic: RGX-314 Dose 1

AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)

Experimental: RGX-314 Dose 2

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

Genetic: RGX-314 Dose 2

AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)

Active Comparator: Control Arm

Aflibercept administered via intravitreal injection approximately every 8 weeks

Biological: Aflibercept (EYLEA®)

2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections Other Names: • Eylea (anti-VEGF agent)

Outcome Measures

Primary Outcome Measures

Mean change from baseline in Best Corrected Visual Acuity (BCVA) [At Week 54]
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)

Secondary Outcome Measures

Incidences of ocular and overall Serious Adverse Events (SAEs) [At Week 54]
Incidences of ocular and overall Serious Adverse Events
Mean change from baseline in BCVA [At Week 54 (RGX-314 randomized participants only)]
BCVA measured by ETDRS
Mean change from baseline in CRT and CPT as measured by SD-OCT [At Week 54 and Week 90]
CRT and CPT as measured by SD-OCT
Mean reduction in supplemental anti VEGF injection annualized rate compared with the prior year of therapy [Through Week 54 and Week 90]
Supplemental anti-VEGF treatments required post therapy to the year prior
Mean supplemental anti VEGF injection annualized rate in the RGX-314 arms [Through Week 54 and Week 90]
Supplemental anti-VEGF treatments required post therapy to the year prior
Aqueous RGX-314 TP concentrations [At Week 14, Week 38, Week 54, Week 74 and Week 90]
Observation of concentration of RGX-314 in the aqueous humor over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 50 years and ≤ 89 years
An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
Diagnosis of subfoveal CNV secondary to AMD in the study eye previously treated with anti-VEGF
Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.
Willing and able to provide written, signed informed consent for this study
Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Exclusion Criteria:

CNV or macular edema in the study eye secondary to any causes other than AMD
Subfoveal fibrosis or atrophy in the study eye
Any condition in the investigator's opinion that could limit VA improvement in the study eye
Active or history of retinal detachment in the study eye
Uncontrolled glaucoma in the study eye
History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1
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.
Prior treatment with gene therapy.
Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Encino location	Encino	California	United States	91436
2	Santa Ana Location	Santa Ana	California	United States	92705
3	Colorado Springs location	Colorado Springs	Colorado	United States	80909
4	Durango Location	Durango	Colorado	United States	81303
5	Gainesville Location	Gainesville	Florida	United States	32607
6	'Aiea location	'Aiea	Hawaii	United States	96701
7	Lemont location	Lemont	Illinois	United States	60439
8	Oak Forest location	Oak Forest	Illinois	United States	60452
9	New Albany Location	New Albany	Indiana	United States	47150
10	Boston Location	Boston	Massachusetts	United States	02114
11	Novi Location	Novi	Michigan	United States	48375
12	Edina Location	Edina	Minnesota	United States	55435
13	Cincinnati Location	Cincinnati	Ohio	United States	45242
14	Edmond Location	Edmond	Oklahoma	United States	73013
15	Memphis Location	Memphis	Tennessee	United States	38138
16	Salt Lake City Location	Salt Lake City	Utah	United States	84107
17	Norfolk location	Norfolk	Virginia	United States	23502