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NCT Number: NCT04704921

Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD

ABBV-RGX-314 (also known as RGX-314) is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD or nAMD). 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 (anti-VEGF) therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to maintain or prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every 4 to 16 weeks in frequency, to maintain efficacy. Due to the burden of these treatments, patients often experience a decline in vision with reduced frequency of treatment over time.

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Key information

Conditions

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

Age range

50 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Retinal Research Institute /ID# 256019, Phoenix, Arizona, United States

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About this study

This randomized, partially masked, active-controlled, Phase 2b/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 ABBV-RGX-314 relative to an active comparator. The primary endpoint of this study is the mean change from baseline in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to ranibizumab at Week 54. Approximately 630 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), and 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 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, as determined by CRC
  • Any condition in the investigator's opinion that could limit VA improvement in the study eye
  • Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye
  • Advanced glaucoma or history of secondary glaucoma in the study eye
  • 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 product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1
  • Prior treatment with gene therapy
  • Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months

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
  • Active or history of retinal detachment, or current retinal tear that cannot be treated 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 (Week -2)
  • History of intravitreal therapy in either eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening
  • Prior treatment with gene therapy (*) For previously treated crossover participants, criteria apply to the eye not treated in the main study only.

Treatment and study plan

ABBV-RGX-314

Genetic

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

Other names: surabgene lomparvovec, RGX-314

Ranibizumab (LUCENTIS®)

Biological

0.5 mg (0.05 mL of 10 mg/mL solution) administered by intravitreal injection approximately every 28 days

Other names: Ranibizumab (anti-VEGF agent)

Primary outcomes

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

    Time frame: At Week 54

    BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)

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

    Time frame: Week 50

    Incidence of ocular AEs and any SAEs

Secondary outcomes

  1. Incidences of ocular and overall AEs over 54 weeks

    Time frame: Through Week 54

    AEs over 54 weeks

  2. Incidences of ocular and overall AEs over 98 weeks

    Time frame: Through Week 98

    AEs over 98 weeks

  3. Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score

    Time frame: Week 98

    BCVA measured by ETDRS

  4. Proportion of participants with worsened BCVA

    Time frame: Week 54; Week 98

    Proportion with worsened BCVA

  5. Proportion of participants with improved BCVA

    Time frame: Week 54; Week 98

    Proportion with improved BCVA

  6. Proportion of participants (1) gaining > 0 letters; (2) losing > 0 letters; maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA

    Time frame: Week 54; Week 98

    Proportion gaining or losing > 0 letters based on ETDRS score; proportion maintaining vision

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

    Time frame: Week 54; Week 98

    Mean change in BCVA based on ETDRS score for participants who received 0 or more supplemental anti-VEGF injection

  8. Mean change from Week 54 to Week 98 in BCVA (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Week 54 to Week 98

    Mean change in BCVA based on ETDRS score

  9. Mean change from baseline in CRT as measured by SD-OCT

    Time frame: Week 54; (ABBV-RGX-314 randomized participants) Week 98

    Mean change in CRT as measured by SD-OCT

  10. Mean change from Week 54 to Week 98 in CRT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314)

    Time frame: from Week 54 to Week 98

    Mean change in CRT as measured by SD-OCT

  11. Mean change from baseline in CPT as measured by SD-OCT

    Time frame: Week 54; (ABBV-RGX-314 randomized participants) Week 98

    Mean change in CPT as measured by SD-OCT

  12. Mean change from Week 54 to Week 98 in CPT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314)

    Time frame: from Week 54 to Week 98

    Mean change in CPT as measured by SD-OCT

  13. Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 98

    Mean number of supplemental anti-VEGF injections

  14. Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 98

    Proportion of participants with 0, 1, 2, and 3 supplemental injections

  15. Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 98

    Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections

  16. Proportion of participants that received 1 or 2 injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Through Week 98

    In the subset of participants who were given supplemental anti-VEGF injections, proportion of participants that received 1 or 2 injections

  17. Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 98

    Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate

  18. Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 98

    Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate

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

    Time frame: Through Week 54 and Week 98

    Supplemental anti-VEGF injection annualized rate

  20. Supplemental anti-VEGF injection annualized rate through Week 54 and Week 98 (ABBV-RGX-314 randomized participants)

    Time frame: Through Week 54 and Week 98

    Supplemental anti-VEGF injection annualized rate

  21. Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 98 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX-314)

    Time frame: After Week 58 through Week 98

    Percent reduction in anti-VEGF injection annualized rate

  22. Supplemental anti-VEGF injection annualized rate after Week 58 through Week 98 (control arm participants who cross over to ABBV-RGX-314)

    Time frame: After Week 58 to Week 98

    Supplemental anti-VEGF injection annualized rate

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

    Time frame: Week 98

    Time to first supplemental anti-VEGF injection

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

    Time frame: After Week 58 to Week 98

    Time to first supplemental anti-VEGF injection

  25. Mean change from baseline in NEI-VFQ-25 (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98

    Time frame: Week 54; Week 98

    Mean change in NEI VGQ-25 (composite score) at week 54 (control arm participants who cross over to ABBV-RGX-314)

  26. Mean change from baseline in MacTSQ (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98

    Time frame: Week 54; Week 98

    Mean change from baseline in MacTSQ (composite score) at week 54 and (control arm participants who cross over to ABBV-RGX-314) at Week 98

  27. Aqueous ABBV-RGX-314 TP concentrations (ABBV-RGX-314 randomized participants)

    Time frame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98

    Aqueous ABBV-RGX-314 TP concentration

  28. Aqueous ABBV-RGX-314 TP concentrations (control arm participants who cross over to ABBV-RGX-314)

    Time frame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98

    Aqueous ABBV-RGX-314 TP concentration

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

    Time frame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98

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

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

    Time frame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98

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

  31. Bilateral Treatment Substudy: Incidence of nonocular AEs and any AEs of special interest

    Time frame: Week 50

    Nonocular AEs and AEs of Special interest

  32. Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed timepoints

    Time frame: Through Week 50

    BCVA measured by ETDRS

  33. Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed timepoints

    Time frame: Through Week 50

    Mean change in CRT as measured by SD-OCT

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

    Time frame: Through Week 50

    Supplemental anti-VEGF injection annualized rate

  35. Bilateral Treatement Substudy: Mean number of supplemental anti-VEGF injections

    Time frame: Through Week 50

    Mean supplemental anti-VEGF injections

  36. 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

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

    Time frame: Wk 26, Wk 34, Wk 50

    Aqueous humor and serum ABBV-RGX-314 TP Concentrations

  38. 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: Wk 18, Wk 34, Wk 50

    Immunogenicity measurements

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • REGENXBIO Inc.

Registry information

Official study 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)

Acronym: ATMOSPHERE

Important dates

Study start
2020
Primary completion
2026
Study completion
2027
First posted
Jan 12, 2021
Registry last updated
Apr 28, 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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