Pivotal 1 Study of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)

• ClinicalTrials.gov Identifier: NCT04704921
• Recruitment Status: Recruiting
• First Posted: January 12, 2021
• Last Update Posted: April 26, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: January 8, 2021
• First Posted Date: January 12, 2021
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: December 29, 2020
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 8, 2021)

Mean change from baseline in Best Corrected Visual Acuity (BCVA) [ Time Frame: At Week 54 ]

BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 8, 2021)

• Incidences of ocular and overall adverse events (AEs) [ Time Frame: Through Week 98 ]
  Evaluate the safety and tolerability of RGX-314
• Mean change from baseline in BCVA [ Time Frame: At Week 98 (RGX-314 randomized participants only) ]
  BCVA measured by ETDRS
• Mean change from baseline in Central Retinal Thickness (CRT) and Center Point Thickness (CPT) as measured by Spectral Domain Optical Coherence Tomography (SD-OCT) [ Time Frame: At Week 54 and Week 98 ]
• Mean reduction in supplemental anti VEGF injection annualized rate compared with the prior 52 weeks preceding the first ranibizumab injection received as part of the Active Run-in Period (RGX 314 randomized participants) [ Time Frame: Through Week 54 and Week 98 ]
• Mean supplemental anti-VEGF injection annualized rate in the RGX-314 arms [ Time Frame: Through Week 54 and Week 98 ]
• Aqueous RGX-314 target protein (TP) concentrations [ Time Frame: At Week 14, Week 26, Week 38, Week 54, and Week 98 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pivotal 1 Study of RGX-314 Gene Therapy in Participants With nAMD
• Official Title: A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)
• 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.
• Detailed Description: This randomized, partially masked, controlled, Phase 2b/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 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 ranibizumab. Approximately 300 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The administration of RGX-314 requires an outpatient surgical procedure performed in an operating room, while the active control, ranibizumab, is administered via intravitreal injection in an office setting. This study will be partially masked which will include masking of key study assessors and study drug dose.

Primary Purpose: Treatment

Condition

• AMD
• nAMD
• Wet Age-related Macular Degeneration
• wAMD
• Wet AMD
• CNV

Intervention

• Genetic: RGX-314
  AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
• Genetic: RGX-314
  AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
• Biological: Ranibizumab (LUCENTIS®)
  0.5 mg (0.05 mL of 10 mg/mL solution) administered by intravitreal injection approximately every 28 days
  Other Name: Ranibizumab (anti-VEGF agent)

Study Arms

• Experimental: RGX-314 Dose 1
  RGX-314 Dose 1 administered via subretinal delivery one time.
  Intervention: Genetic: RGX-314
• Experimental: RGX-314 Dose 2
  RGX-314 Dose 2 administered via subretinal delivery one time.
  Intervention: Genetic: RGX-314
• Active Comparator: Control Arm
  Ranibizumab administered via intravitreal injection approximately every 28 days
  Intervention: Biological: Ranibizumab (LUCENTIS®)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 8, 2021): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2026
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 in the study eye
5. Uncontrolled glaucoma in the study eye
6. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1
7. 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.
8. Prior treatment with gene therapy.
9. Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

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: NCT04704921
• Other Study ID Numbers: RGX-314-2104
• 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: No

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: April 2024