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

• ClinicalTrials.gov Identifier: NCT04514653
• Recruitment Status: Recruiting
• First Posted: August 17, 2020
• Last Update Posted: May 22, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

RGX-314 is being developed as a potential novel one-time gene therapy treatment 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 twelve 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.

Condition or disease	Intervention/treatment	Phase
Neovascular Age-Related Macular Degeneration (nAMD)	Genetic: RGX-314 Dose 1; Genetic: RGX-314 Dose 2; Biological: Ranibizumab; Genetic: RGX-314 Dose 3; Drug: Local steroid; Drug: Topical steroid	Phase 2

Detailed Description:

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with nAMD. Approximately 115 participants who meet the inclusion/exclusion criteria will be enrolled into one of 6 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive RGX-314 or ranibizumab control, and participants enrolled in Cohorts 3 through 5 will receive RGX-314. Participants enrolled in Cohort 6 will receive RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Cohort 1 will evaluate RGX-314 Dose 1, Cohorts 2 and 3 will evaluate RGX-314 Dose 2, and Cohorts 4, 5, and 6 will evaluate RGX-314 Dose 3. Participants will be evaluated for efficacy, safety and tolerability of RGX-314 throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: The vision examiners and central reading center (CRC) graders will be masked, meaning they will be unaware of the participants' treatment assignment. All other individuals affiliated with the study (investigators, all study center personnel apart from the vision examiners, the participants, all Sponsor staff, all staff affiliated with the contract research organization, and all CRC staff apart from the CRC graders) will have knowledge of the treatment assignment.
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Dose-escalation, Ranibizumab-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via One or Two Suprachoroidal Space (SCS) Injections in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)
• Actual Study Start Date: August 25, 2020
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: January 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ranibizumab control; Control treatment arm	Biological: Ranibizumab; Ranibizumab (anti-VEGF agent)
Experimental: RGX-314 Treatment Arm (Dose 1); RGX-314 Dose 1	Genetic: RGX-314 Dose 1; AAV8 vector containing a transgene for anti-VEGF fab (Dose 1); Other Name: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 2); RGX-314 Dose 2	Genetic: RGX-314 Dose 2; AAV8 vector containing a transgene for anti-VEGF fab (Dose 2); Other Name: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 3); RGX-314 Dose 3	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Name: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 3) and Local Steroid; RGX-314 Dose 3 and Local Steroid	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Name: Combination Product; Drug: Local steroid; Local Steroid
Experimental: RGX-314 Treatment Arm (Dose 3) and Topical Steroid; RGX-314 Dose 3 and Topical Steroid	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Name: Combination Product; Drug: Topical steroid; Topical steroid

Outcome Measures

Primary Outcome Measures :

1. To evaluate the mean change in Best Corrected Visual Acuity (BCVA) for RGX-314 compared with ranibizumab monthly. [ Time Frame: 40 weeks ]
   The scale used is the early treatment diabetic retinopathy study (ETDRS) letter score from 0-100 and higher score being better vision.

Secondary Outcome Measures :

1. Evaluate the safety and tolerability of RGX-314 [ Time Frame: 52 weeks ]
   Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)
2. Evaluate the incidence of ocular inflammation following administration of RGX-314 [ Time Frame: 52 weeks ]
   Proportion of participants who experience ocular inflammation following SCS RGX-314 administration
3. Evaluate the effect of RGX-314 on choroidal neovascularization (CNV) lesion growth and leakage [ Time Frame: 52 weeks ]
   Mean change from baseline in CNV lesion size and leakage area based on fluorescein angiography (FA) at Week 52.
4. Evaluate the effect of RGX-314 on BCVA [ Time Frame: 52 weeks ]
   Mean change from baseline in BCVA to Week 52
5. Evaluate the effect of RGX-314 on central retinal thickness (CRT) [ Time Frame: 52 weeks ]
   Mean change from baseline in CRT as measured by spectral domain-optical coherence tomography (SD-OCT) to Week 40 and Week 52
6. Assess the need for supplemental anti-vascular endothelial growth factor (VEGF) therapy in participants who receive RGX-314 treatment [ Time Frame: 52 weeks ]
   Mean supplemental anti-VEGF injection annualized rate in the RGX-314 treatment arm through Week 40 and Week 52
7. Evaluate the concentration of RGX-314 transgene product (TP) in aqueous humor and serum [ Time Frame: 52 weeks ]
   Mean change from baseline and Week 54 in serum RGX-314 TP concentration over time

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 ONLY:

  • Active or history of glaucoma or ocular hypertension 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.

Contacts and Locations

Contacts

Contact: Patient Advocacy; 1-866-860-0117; patientadvocacy@regenxbio.com

Locations

United States, Arizona

Phoenix Location; Recruiting

Phoenix, Arizona, United States, 85014

Contact: Principal Investigator

United States, California

Bakersfield Location; Active, not recruiting

Bakersfield, California, United States, 93309

Beverly Hills Location; Recruiting

Beverly Hills, California, United States, 90211

Contact: Principal Investigator

Mountain View Location; Recruiting

Mountain View, California, United States, 94040

Contact: Principal Investigator

Poway Location; Recruiting

Poway, California, United States, 92064

Contact: Principal Investigator

Santa Barbara Location; Active, not recruiting

Santa Barbara, California, United States, 93103

United States, Georgia

Augusta Location; Recruiting

Augusta, Georgia, United States, 30909

Contact: Principal Investigator

United States, Maryland

Baltimore Location; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Principal Investigator

United States, Massachusetts

Boston Location; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Principal Investigator

United States, Nevada

Reno Location; Recruiting

Reno, Nevada, United States, 89502

Contact: Principal Investigator

United States, New Mexico

Albuquerque Location; Recruiting

Albuquerque, New Mexico, United States, 87109

Contact: Principal Investigator

United States, Pennsylvania

Philadelphia Location; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contact: Principal Investigator

United States, Tennessee

Germantown Location; Active, not recruiting

Germantown, Tennessee, United States, 38138

Nashville Location; Active, not recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

Woodlands Location; Active, not recruiting

The Woodlands, Texas, United States, 77384

Sponsors and Collaborators

AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT04514653
• Other Study ID Numbers: RGX-314-2102
• First Posted: August 17, 2020
• Last Update Posted: May 22, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by AbbVie:

AMD; wet AMD; wAMD; nAMD

Additional relevant MeSH terms:

Macular Degeneration; Wet Macular Degeneration; Choroidal Effusions; Retinal Degeneration; Retinal Diseases; Eye Diseases; Eye Abnormalities; Choroid Diseases; Uveal Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents