RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)

AbbVie

Status and phase: Enrolling; Phase 2

Conditions: Neovascular Age-Related Macular Degeneration (nAMD)

Treatments: Genetic: ABBV-RGX-314 Dose 3; Genetic: ABBV-RGX-314 Dose 2; Drug: Local Steroid; Biological: Ranibizumab; Drug: Topical Steroid; Genetic: ABBV-RGX-314 Dose 1; Genetic: ABBV-RGX-314 Dose 4

Study type: Interventional

Funder types: Industry

Identifiers

NCT04514653

M23-411 (Other Identifier)

RGX-314-2102 (M23-411)

Details and patient eligibility

About

This interventional study is being conducted with an investigational gene therapy treatment called ABBV-RGX-314 (also known as RGX-314) and is being developed as a potential one-time gene therapy treatment for neovascular (wet) age-related macular degeneration (wet AMD or nAMD). The typical treatment for nAMD is frequent injections of anti-VEGF therapy. Researchers are testing ABBV-RGX-314 to see if it has similar effects as the current approved standard of care, such as Lucentis® or Eylea® injections.

The duration of this study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314 after week 52, up to 80 weeks post-randomization.

The primary outcome measure for this investigational study is to evaluate the mean change in best-corrected visual acuity (BCVA) for ABBV-RGX-314 compared with ranibizumab monthly at the Week 40 visit.

Full description

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 gene therapy in subjects with nAMD.

ABBV-RGX-314 will be injected into the SCS part of the eye. Approximately 140 participants who meet the inclusion/exclusion criteria will be enrolled into one of 7 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive ABBV-RGX-314 or the intravitreal ranibizumab control. Participants enrolled in Cohorts 3 through 5 will receive ABBV-RGX-314. Participants enrolled in Cohort 6 will receive ABBV-RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Participants randomized in Cohort 7 will receive ABBV-RGX-314 with a protocol mandated steroid regimen or the intravitreal ranibizumab control. Cohort 1 will evaluate ABBV-RGX-314 Dose 1, Cohorts 2 and 3 will evaluate ABBV-RGX-314 Dose 2, Cohorts 4, 5, and 6 will evaluate ABBV-RGX-314 Dose 3, and Cohort 7 will evaluate ABBV-RGX-314 Dose 4.

The duration of the study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314, up to 80 weeks post-randomization.

Enrollment: 140 estimated patients

Sex: All

Ages: 50 to 89 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >/= 50 and </= 89
• Diagnosis of CNV secondary to age-related macular degeneration in the study eye.
• Participants must have demonstrated a meaningful response to anti-VEGF therapy.
• Willing and able to provide written, signed informed consent for this study.

Exclusion criteria

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• Subfoveal fibrosis or atrophy in study eye.
• Participants who have had a prior vitrectomy.
• Active or history of retinal detachment in the study eye.
• History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product (IP), other than anti-VEGF therapy, in the 6 months prior to study entry.
• Received any gene therapy.
• Any condition preventing visualization of the fundus or VA improvement in the study eye, eg, cataract.
• History of intraocular surgery in the study eye within 12 weeks of study entry.
• Receipt of any IP within 30 days of study entry or 5 half-lives of the IP.
• Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within 6 months of study entry.
• Cohorts 1 - 5 only: Uncontrolled glaucoma in the study eye.

COHORT 6 AND 7 ONLY:

• Active or history of glaucoma or ocular hypertension (steroid-induced ocular hypertension (Cohort 7 only)) in the study eye.
• Certain OCT characteristics including: Large Pigment Epithelial Detachments (PED), clinically significant Epiretinal Membrane (ERM) in the study eye at Visit 1.

Note: Other inclusion/exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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140 participants in 7 patient groups

Ranibizumab control

Active Comparator group

Description:

Control treatment arm

Treatment:

Biological: Ranibizumab

ABBV-RGX-314 Treatment Arm (Dose 1)

Experimental group

Description:

ABBV-RGX-314 Dose 1

Treatment:

Genetic: ABBV-RGX-314 Dose 1

ABBV-RGX-314 Treatment Arm (Dose 2)

Experimental group

Description:

ABBV-RGX-314 Dose 2

Treatment:

Genetic: ABBV-RGX-314 Dose 2

ABBV-RGX-314 Treatment Arm (Dose 3)

Experimental group

Description:

ABBV-RGX-314 Dose 3

Treatment:

Genetic: ABBV-RGX-314 Dose 3

ABBV-RGX-314 Treatment Arm (Dose 3) and Local Steroid

Experimental group

Description:

ABBV-RGX-314 Dose 3 and Local Steroid

Treatment:

Drug: Local Steroid

Genetic: ABBV-RGX-314 Dose 3

ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid

Experimental group

Description:

ABBV-RGX-314 Dose 3 and Topical Steroid

Treatment:

Drug: Topical Steroid

Genetic: ABBV-RGX-314 Dose 3

ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid

Experimental group

Description:

ABBV-RGX-314 Dose 4 and Topical Steroid

Treatment:

Genetic: ABBV-RGX-314 Dose 4

Drug: Topical Steroid