Ixoberogene Soroparvovec (Ixo-vec) Contralateral Dosing Study in Participants With Neovascular Age-related Macular Degeneration

Evaluation of the Safety and Tolerability of Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy in the Second (Contralateral) Eye of Participants With Bilateral Neovascular Age-related Macular Degeneration.

The purpose of this study is to evaluate safety, effectiveness and durability of a gene therapy called Ixo-vec (Ixoberogene soroparvovec) when administered to the contralateral (second) eye of adult participants (≥ 50 years of age) who have been diagnosed with bilateral neovascular (wet) age related macular degeneration (nAMD). The study will enroll adults with nAMD in both eyes, including participants who previously received Ixo-vec treatment in one (initial) eye and/or participants who will receive Ixo-vec treatment for the first time. This study focuses on how the treatment works when both eyes are treated at different times and how effective and long-lasting Ixo-vec treatment is in the second (contralateral) eye.

Participants will receive a single administration of Ixo-vec in the contralateral eye and will be followed for approximately 5 years to evaluate safety, efficacy and durability of contralateral treatment. Secondary objectives include assessments that will evaluate clinical activity, including visual and anatomic outcomes, as well as the need for supplemental anti-VEGF therapy.

The study is intended to provide additional information on the safety, tolerability, and use of Ixo-vec in bilateral treatment.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-Related Macular Degeneration (nAMD) Wet AMD
• Intervention / Treatment: Genetic: Ixo-vec

Detailed Description

This is a Phase 2, single-arm, open-label, multi-center study in participants who are ≥ 50 years old with a diagnosis of bilateral choroidal neovascularization (CNV) secondary to neovascular (wet) age related macular degeneration (nAMD). This study is designed to evaluate the safety, tolerability, and efficacy of Ixo-vec dosing in the contralateral (second) eye.

The study includes participants who have previously received Ixo-vec in one eye in a prior clinical study, as well as Ixo-vec-naïve participants eligible for sequential bilateral administration. The study will evaluate the use of Ixo-vec when both eyes are treated at different time points.

Neovascular AMD is a progressive retinal disease characterized by the growth of abnormal blood vessels originating from the choroid, which can lead to vision loss. Current standard of care includes repeated intravitreal (IVT) administration of anti-vascular endothelial growth factor (anti-VEGF) therapies.

Ixo-vec (also known as Ixoberogene soroparvovec, ADVM-022 or AAV.7m8-aflibercept) is an adeno-associated virus (AAV)-based gene therapy designed to enable sustained intraocular expression of an anti-VEGF protein following a single IVT administration.

The primary objective of this study is to assess the safety and tolerability of Ixo-vec administered to the contralateral eye. Secondary objectives include assessments that will evaluate clinical activity, including visual and anatomic outcomes, as well as the need for supplemental anti-VEGF therapy over time.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adverum Study Contact; Phone Number: 650-656-9323; Email: ADVM02214ClinOp@adverum.com

Study Locations

• United States
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Not yet recruiting
      • Adverum site 124
    • Fort Lauderdale, Florida, United States, 33308
      • Recruiting
      • Adverum site 176
    • Jacksonville, Florida, United States, 32216
      • Not yet recruiting
      • Adverum site 168
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Recruiting
      • Adverum site 122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

1. Male or female, aged ≥ 50 years at Screening Visit 1.
2. Must agree to use an acceptable form of contraception.
3. Have diagnosis of bilateral CNV secondary to nAMD.

4. Meet ETDRS BCVA letter score criteria:

   • For Ixo-vec-experienced participants: Contralateral eye has an ETDRS BCVA letter score within a protocol-defined range appropriate for nAMD clinical trials.
   • For Ixo-vec-naïve participants: Both the initial eye and contralateral eye have ETDRS BCVA letter score within a protocol-defined range appropriate for nAMD clinical trials
5. Have prior treatment history consistent with protocol-defined requirements, including prior anti-VEGF therapy and, where applicable, prior Ixo-vec exposure.
6. Demonstrate a meaningful anatomic response to anti-VEGF in the contralateral eye (all participants) and in the initial eye (Ixo-vec-naïve participants only). Meaningful anatomic response to prior anti-VEGF therapy as defined in the protocol.
7. Able to comply with study procedures according to the Investigator's judgment.

Other protocol-defined INCLUSION CRITERIA apply.

EXCLUSION CRITERIA:

A/ General Exclusion Criteria

1. Have history of a medical condition (systemic disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding) giving reasonable suspicion of a condition that contraindicates the use of Ixo-vec, compromises the participant's ability to comply with the planned study assessments, or that might affect the interpretation of the results of the study or render the participant at high risk for treatment complications in the opinion of the Investigator. History of severe coronavirus disease of 2019 (COVID-19) infection may meet this exclusion criterion if, in the opinion of the Investigator, it is likely to lead to any of the complications listed above.
2. Received prior gene therapy (other than Ixo-vec, where applicable)
3. Currently receiving steroids at Screening Visit 1 in the previously treated eye (Ixo-vec-experienced participants) or in either eye (Ixo-vec-naïve participants).
4. Received any non-gene IMP or medical device in the contralateral eye (and/or initial eye for Ixo-vec-naïve participants) within 3 months of Screening Visit 1
5. Have history of allergy, hypersensitivity, or contraindications to the use of any product or its excipients administered as part of this study.
6. Have evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0%
7. Have history or evidence of cardiovascular diseases and ongoing bleeding disorders as defined by the protocol.
8. Use of systemic immunosuppressive therapy within a protocol-defined period.
9. Received systemic anti-VEGF therapy within a protocol-defined period.

10. Have history of malignancy within the 5 years prior to Screening Visit 1, except for adequately treated malignancies as defined by the protocol.

    B/Ocular Exclusion Criteria

11. Have any active ocular or periocular infection in the contralateral eye in the contralateral eye (all participants) or in the initial eye (Ixo-vec-naïve participants only).
12. Have any history or evidence of a concurrent intraocular condition in the contralateral eye (all participants) or in the initial eye (Ixo-vec-naïve participants only), including retinal diseases other than nAMD, that, in the judgment of the Investigator, could reduce the potential for visual improvement, confound assessment of the macula or require medical or surgical intervention during the study.
13. Have prior ocular surgery or treatment that may confound assessment or increase risk.
14. Have any history or evidence of retinal detachment (with or without repair) or retinal pigment epithelium rip/tear in the contralateral eye (all participants) or in the initial eye (Ixo-vec-naïve participants only), as determined by the Investigator.
15. Have uncontrolled ocular hypertension or glaucoma as defined by the protocol.
16. Have any history of inflammatory anterior chamber cell or vitreous cell ≥ 2+ in the initial eye, that, in the opinion of the Investigator and Sponsor, predisposes the contralateral eye to a heightened risk of intraocular inflammation. Enrollment of a participant with prior anterior chamber cell or vitreous cell ≥2+ in the initial eye requires discussion with the medical monitor.

Other protocol-defined EXCLUSION CRITERIA apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ixo-vec dosing in Contralateral Eye; Population of Ixo-vec-Experienced or Ixo-vec Naïve Participants.	Genetic: Ixo-vec; Ixo-vec (6 × 10^10 vg/eye) will be administered intravitreally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ocular adverse events (AEs)	The number of participants who experience an ocular adverse event will be summarized.	Baseline through Week 28
Incidence of ocular serious adverse events (SAEs).	The number of participants who experience ocular serious adverse event will be summarized.	Baseline through Week 28
Incidence of non-ocular serious adverse events (SAEs).	The number of participants who experience non-ocular serious adverse event will be summarized.	Baseline through Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in best corrected visual acuity (BCVA) over time through Week 28.	BCVA will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart.	Baseline through Week 28
Mean change from baseline in central subfield thickness (CST) over time through Week 28.	CST as measured by spectral domain optical coherence tomography (SD-OCT).	Baseline through Week 28
Mean number of supplemental aflibercept IVT injections received from Week 4 through Week 28	Efficacy will be measured by the number of supplemental aflibercept injections post Ixo-vec administration.	Week 4 through Week 28
Percentage of participants who are supplemental aflibercept injection-free through Week 28.	Efficacy will be measured as the percentage of participants who will not received supplemental aflibercept injections post Ixo-vec administration.	Baseline through Week 28

Collaborators and Investigators

• Sponsor: Adverum Biotechnologies, Inc.
• Investigators: Study Director: Adam Turpcu, PhD, Adverum Biotechnologies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: macular degeneration; AMD; gene therapy; Neovascular AMD; Aflibercept; AAV; Neovascular age-related macular degeneration; wet AMD; CNV; Blindness; ADVM-022; AAV.7m8; AAV.7m8-aflibercept; Eye disease; wAMD; nAMD; AAV vector; ADVM; Wet Age-related Macular Degeneration; Ixoberogene soroparvovec; Ixo-vec; Adeno-associated viruses; neovascular macular degeneration; contralateral; ADVM-022-14
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Vision Disorders; Sensation Disorders; Retinal Diseases; Retinal Degeneration; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Eye Diseases; Macular Degeneration; Blindness
• Other Study ID Numbers: ADVM-022-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Adverum is committed to transparency. Appropriately de-identified participant-level data and supporting documents may be shared under appropriate conditions (e.g. when contractually permitted and when participants provide appropriate consent). Individual patient-level data would only be shared following completion of this study (and any associated studies), completion of applicable regulatory submissions, and in accordance with applicable regulations and laws, as well as criteria established by Adverum, our collaborators and/or industry best practices. Shared datasets and/or documents may be de-identified and/or redacted to protect participant identity and to protect sensitive and confidential information. For inquiries, please contact us at datasharing@adverum.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No