Home › Trials › NCT04704921

One-time gene therapy for wet age-related macular degeneration

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)

PHASE2; PHASE3 · AbbVie · NCT04704921

This study is testing a one-time gene therapy for people with wet age-related macular degeneration to see if it can improve their vision better than current treatments that require regular injections.

Quick facts

PhasePHASE2; PHASE3
Study typeInterventional
Enrollment540 (estimated)
Ages50 Years to 89 Years
SexAll
SponsorAbbVie (industry)
Drugs / interventionsranibizumab
Locations91 sites (Phoenix, Arizona and 90 other locations)
Trial IDNCT04704921 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates ABBV-RGX-314, a novel gene therapy administered via subretinal delivery for treating neovascular age-related macular degeneration (nAMD). The study is randomized and partially masked, comparing two dose levels of ABBV-RGX-314 against an active control, ranibizumab, to assess efficacy and safety. Approximately 540 participants aged 50 to 89 with a history of anti-VEGF treatment will be enrolled, and the primary outcome will measure changes in best-corrected visual acuity over 54 weeks. This approach aims to reduce the treatment burden associated with frequent injections required by current therapies.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 89 with a diagnosis of nAMD who have previously responded to anti-VEGF therapy.

Not a fit: Patients with other causes of choroidal neovascularization or significant retinal damage may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could significantly improve vision outcomes for patients with wet AMD while reducing the need for frequent injections.

How similar studies have performed: Other studies have shown promise with gene therapy approaches for retinal diseases, indicating potential for success with this novel treatment.

Eligibility criteria

Show full inclusion / exclusion 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, as determined by CRC
3. Any condition in the investigator's opinion that could limit VA improvement in the study eye
4. Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye
5. Advanced glaucoma or history of secondary glaucoma in the study eye
6. History of intraocular surgery in the study eye within 12 weeks prior to randomization
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

Where this trial is running

Phoenix, Arizona and 90 other locations

+41 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: AMD, nAMD, Wet Age-related Macular Degeneration, wAMD, Wet AMD, CNV, Neovascular AMD, Neovascular Age-related Macular Degeneration

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.