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NCT Number: NCT05407636

Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD

ABBV-RGX-314 (also known as RGX-314 and surabgene lomparvovec (sura-vec)) 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-vascular endothelial growth factor (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. ABBV-RGX-314 is being developed as a potential one-time treatment for wet AMD.

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Key information

Conditions

AMD CNV Choroid Diseases Choroidal Neovascularization Eye Diseases Eye Diseases, Hereditary Macular Degeneration Metaplasia Neovascularization, Pathologic Pathologic Processes Pathological Conditions, Signs and Symptoms Retinal Degeneration Retinal Diseases Uveal Diseases Wet Age-related Macular Degeneration Wet Macular Degeneration nAMD wAMD wetAMD

Age range

50 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Calgary Retina Consultants /ID# 258997, Calgary, Alberta, Canada

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About this study

This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to aflibercept. Approximately 714 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

A bilateral treatment substudy conducted at US sites is an open-label, partially randomized, parallel arm study to evaluate the safety and efficacy of subretinal ABBV-RGX-314 administered bilaterally in participants who have bilateral nAMD. Previously treated crossover participants from the control arm of the main study who crossed over and received ABBV-RGX-314 in the study eye will receive the same ABBV-RGX-314 dose in the contralateral eye (ie, same dose as in the study eye), while newcomers (participants who have not been randomized in an ABBV-RGX-314 study) and untreated crossover participants (ongoing control participants in the main study who have completed Week 54 but have not crossed over to receive ABBV-RGX-314 in the main study) will be randomized in a 2:1 ratio to receive ABBV-RGX-314 Dose 1 or ABBV-RGX-314 Dose 2 in both eyes. Up to 15 participants who qualify for the substudy will be enrolled and followed for a minimum of 50 weeks.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 50 years and ≤ 89 years
  • An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
  • Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in the study eye previously treated with anti-VEGF
  • Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye
  • Willing and able to provide written, signed informed consent for this study
  • Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Inclusion criteria

(Bilateral Treatment Substudy)*:

  • An ETDRS BCVA letter score between ≤ 83 and ≥ 40 in both eyes
  • Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in both eyes
  • Must be pseudophakic (at least 12 weeks postcataract surgery) in both eyes
  • Willing and able to provide written, signed informed consent for this study
  • Newcomers must have active disease in the study eye; crossover participants must have active disease in the eye not treated in the main study

Exclusion criteria

  • CNV or macular edema in the study eye secondary to any causes other than AMD
  • Subfoveal fibrosis or atrophy in the study eye
  • Any condition in the investigator's opinion that could limit VA improvement in the study eye
  • Advanced glaucoma or history of secondary glaucoma in the study eye
  • Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
  • History of intraocular surgery in the study eye within 12 weeks prior to randomization
  • History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -6
  • Prior treatment with gene therapy

Exclusion criteria

(Bilateral Treatment Substudy)*:

  • CNV or macular edema in either eye secondary to any causes other than AMD
  • Subfoveal fibrosis or atrophy in either eye
  • Any condition in the investigator's opinion that could limit VA improvement in either eye
  • Advanced glaucoma or history of secondary glaucoma in either eye
  • Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
  • History of intraocular surgery in either eye within 12 weeks prior to randomization
  • History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -6.
  • Prior treatment with gene therapy (*) For previously treated crossover participants, criteria apply to the eye not treated in the main study only.

Note: Other inclusion/exclusion criteria apply

Treatment and study plan

ABBV-RGX-314 Dose 1

Genetic

AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)

Other names: RGX-314, surabgene lomparvovec

ABBV-RGX-314 Dose 2

Genetic

AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)

Other names: RGX-314, surabgene lomparvovec

Aflibercept (EYLEA®)

Biological

2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections

Other names: Eylea (anti-VEGF agent)

Primary outcomes

  1. Mean change from baseline in Best Corrected Visual Acuity (BCVA)

    Time frame: At Week 54

    To evaluate the noninferiority of ABBV-RGX-314 relative to aflibercept in mean change from Baseline BCVA at Week 54

  2. Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs

    Time frame: Week 50

    AEs and SAEs through Week 50

Secondary outcomes

  1. Incidences of ocular and overall AEs

    Time frame: Through Week 54

    To evaluate the safety and tolerability of ABBV-RGX-314 through Week 54

  2. Proportion of participants with improved BCVA

    Time frame: Week 54

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

  3. Proportion of participants with worsened BCVA

    Time frame: Week 54

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

  4. Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA

    Time frame: Week 54

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

  5. Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injection (ABBV-RGX- 314 randomized participants)

    Time frame: Week 54

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

  6. Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Week 54 to Week 108

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA

  7. Mean change in central retinal thickness (CRT) as measured by SD-OCT

    Time frame: Through Week 108

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CRT as measured by SD-OCT

  8. Mean change in central point thickness (CPT) as measured by SD-OCT

    Time frame: Through Week 108

    To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CPT as measured by SD-OCT

  9. Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  10. Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  11. Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  12. Proportion of participants that received 1 or 2 injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  13. Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  14. Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  15. Percent reduction in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  16. Supplemental anti-VEGF injection annualized rate through Week 54 (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  17. Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 108 relative to the year prior to study (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  18. Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  19. Time to first supplemental anti- VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  20. Time to first supplemental anti-VEGF injection after the Week 58 injection (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

  21. Mean change from Baseline in NEI VFQ-25 (composite score) at Week 54 and (control arm participants who cross over to ABBV-RGX-314) Week 108

    Time frame: Week 54 and Week 108

    To evaluate patient-reported visual function and treatment satisfaction using PRO questionnaires

  22. Mean change from Baseline in MacTSQ (composite score) at Week 54 and (control arm participants who cross over to ABBV-RGX-314) Week 108

    Time frame: Week 54 and Week 108

    To evaluate patient-reported visual function and treatment satisfaction using PRO questionnaires

  23. Aqueous humor ABBV-RGX-314 TP concentrations at Week -2, Week 14, Week 38, and Week 54 (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54

    To assess aqueous humor and serum TP concentrations prior to and after ABBV-RGX-314 administration

  24. Aqueous humor ABBV-RGX-314 TP concentrations at Week 54, Week 74, Week 90, and Week 108 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 108

    To assess aqueous humor and serum TP concentrations prior to and after ABBV-RGX-314 administration

  25. Serum ABBV-RGX-314 TP concentrations (at select sites)

    Time frame: Through Week 54

    To assess aqueous humor and serum TP concentrations prior to and after ABBV-RGX-314 administration

  26. Immunogenicity measurements (ABBV-RGX-314 randomized participants)

    Time frame: Week -2, Week 14, Week 38, and Week 54

    Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBVRGX- 314 TP)

  27. Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Week 54, Week 74, Week 90, and Week 108

    Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX- 314 TP)

  28. Bilateral Treatment Substudy: Incidence of nonocular AEs and any AESIs

    Time frame: Week 50

    To evaluate the safety and tolerability of bilateral treatment of ABBV-RGX-314 gene therapy

  29. Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed time points

    Time frame: Week 50

    BCVA measured by ETDRS

  30. Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed time points

    Time frame: Through Week 50

    Mean change in CRT as measured by SD-OCT

  31. Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate

    Time frame: Through Week 50

    Supplemental anti-VEGF injection annualized rate

  32. Bilateral Treatment Substudy: Mean number of supplemental anti-VEGF injections

    Time frame: Through Week 50

    Mean supplemental anti-VEGF injections

  33. Bilateral Treatment Substudy: Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections

    Time frame: Through Week 50

    Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections

  34. Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations

    Time frame: Week 26, Week 34, Week 50

    Aqueous humor and serum ABBV-RGX-314 TP concentrations

  35. Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum anti-AAV8 antibodies) and enzyme-linked immunospot at assessed time points

    Time frame: Week 50

    Immunogenicity measurements

Study contacts

Contact information is provided by the study sponsor or research team.

Patient Advocacy

CONTACT

[email protected]

1-833-711-0349

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • REGENXBIO Inc.

Registry information

Official study title

A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD

Acronym: ASCENT

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Jun 7, 2022
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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