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

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ClinicalTrials.gov Identifier: NCT04704921
Recruitment Status : Recruiting
First Posted : January 12, 2021
Last Update Posted : January 12, 2021
Sponsor:
Information provided by (Responsible Party):
Regenxbio Inc.

Tracking Information
First Submitted Date  ICMJE January 8, 2021
First Posted Date  ICMJE January 12, 2021
Last Update Posted Date January 12, 2021
Actual Study Start Date  ICMJE December 29, 2020
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pivotal 1 Study of RGX-314 Gene Therapy in Participants With nAMD
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE 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  ICMJE
  • AMD
  • nAMD
  • Wet Age-related Macular Degeneration
  • wAMD
  • Wet AMD
  • CNV
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 8, 2021)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patient Advocacy 1-866-860-0117 patientadvocacy@regenxbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04704921
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Regenxbio Inc.
Study Sponsor  ICMJE Regenxbio Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Regenxbio Inc.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP