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

Tracking Information

• First Submitted Date: August 4, 2020
• First Posted Date: August 17, 2020
• Last Update Posted Date: May 22, 2023
• Actual Study Start Date: August 25, 2020
• Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2020)

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.

• Original Primary Outcome Measures (submitted: August 14, 2020): To evaluate the mean change in BCVA for RGX-314 compared with ranibizumab monthly. [ Time Frame: 40 weeks ]

Current Secondary Outcome Measures (submitted: October 17, 2022)

• 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)
• 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
• 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.
• Evaluate the effect of RGX-314 on BCVA [ Time Frame: 52 weeks ]
  Mean change from baseline in BCVA to Week 52
• 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
• 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
• 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

Original Secondary Outcome Measures (submitted: August 14, 2020)

• Incidences of overall and ocular AEs and SAEs [ Time Frame: 52 weeks ]
  Evaluate the safety and tolerability of RGX
• 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 FA at Week 40 and Week 52.
• Evaluate the effect of RGX-314 on BCVA [ Time Frame: 52 weeks ]
  Mean change from baseline in BCVA to Week 52
• Evaluate the effect of RGX-314 on central retinal thickness (CRT) [ Time Frame: 52 weeks ]
  Mean change from baseline in CRT as measured by SD-OCT to Week 40 and Week 52
• Assess the need for supplemental anti-vascular endothelial growth factor (VEGF) therapy in participants who receive RGX-314 treatment [ Time Frame: 52 weeks ]
  Annualized supplemental anti-VEGF injection rate through Week 40 and Week 52

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD)
• 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)
• 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.
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Neovascular Age-Related Macular Degeneration (nAMD)

Intervention

• Genetic: RGX-314 Dose 1
  AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)
  Other Name: Combination Product
• Genetic: RGX-314 Dose 2
  AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)
  Other Name: Combination Product
• Biological: Ranibizumab
  Ranibizumab (anti-VEGF agent)
• 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
• Drug: Topical steroid
  Topical steroid

Study Arms

• Active Comparator: Ranibizumab control
  Control treatment arm
  Intervention: Biological: Ranibizumab
• Experimental: RGX-314 Treatment Arm (Dose 1)
  RGX-314 Dose 1
  Intervention: Genetic: RGX-314 Dose 1
• Experimental: RGX-314 Treatment Arm (Dose 2)
  RGX-314 Dose 2
  Intervention: Genetic: RGX-314 Dose 2
• Experimental: RGX-314 Treatment Arm (Dose 3)
  RGX-314 Dose 3
  Intervention: Genetic: RGX-314 Dose 3
• Experimental: RGX-314 Treatment Arm (Dose 3) and Local Steroid
  RGX-314 Dose 3 and Local Steroid
  Interventions:

  • Genetic: RGX-314 Dose 3
  • Drug: Local steroid
• Experimental: RGX-314 Treatment Arm (Dose 3) and Topical Steroid
  RGX-314 Dose 3 and Topical Steroid
  Interventions:

  • Genetic: RGX-314 Dose 3
  • Drug: Topical steroid

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 17, 2022): 115
• Original Estimated Enrollment (submitted: August 14, 2020): 40
• Estimated Study Completion Date: January 2024
• Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04514653
• Other Study ID Numbers: RGX-314-2102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: REGENXBIO Inc.
• Current Study Sponsor: AbbVie
• Original Study Sponsor: REGENXBIO Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AbbVie
• Verification Date: May 2023