Neovascular Age-Related Macular Degeneration (nAMD) Wet AMD
Conditions
Keywords
macular degeneration, AMD, neovascular macular degeneration, gene therapy, contralateral, Ixoberogene soroparvovec, Ixo-vec, Aflibercept, Neovascular age-related macular degeneration, nAMD, wAMD, ADVM, ADVM-022, wet AMD, Wet Age-related Macular Degeneration, CNV, Neovascular AMD, AAV, AAV vector, AAV.7m8-aflibercept, AAV.7m8, Eye disease, Blindness, Adeno-associated viruses, ADVM-022-14
Brief summary
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.
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.
Interventions
GENETICIxo-vec
Ixo-vec (6 × 10\^10 vg/eye) will be administered intravitreally
Sponsors
Adverum Biotechnologies, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants previously treated in one eye (initial eye) and/or treatment-naive participants will receive sequential bilateral administration, with dosing in the contralateral eye.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of ocular adverse events (AEs) | Baseline through Week 28 | The number of participants who experience an ocular adverse event will be summarized. |
| Incidence of ocular serious adverse events (SAEs). | Baseline through Week 28 | The number of participants who experience ocular serious adverse event will be summarized. |
| Incidence of non-ocular serious adverse events (SAEs). | Baseline through Week 28 | The number of participants who experience non-ocular serious adverse event will be summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in best corrected visual acuity (BCVA) over time through Week 28. | Baseline through Week 28 | BCVA will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. |
| Mean change from baseline in central subfield thickness (CST) over time through Week 28. | Baseline through Week 28 | CST as measured by spectral domain optical coherence tomography (SD-OCT). |
| Mean number of supplemental aflibercept IVT injections received from Week 4 through Week 28 | Week 4 through Week 28 | Efficacy will be measured by the number of supplemental aflibercept injections post Ixo-vec administration. |
| Percentage of participants who are supplemental aflibercept injection-free through Week 28. | Baseline through Week 28 | Efficacy will be measured as the percentage of participants who will not received supplemental aflibercept injections post Ixo-vec administration. |
Countries
United States
Contacts
CONTACTAdverum Study Contact
STUDY_DIRECTORAdam Turpcu, PhD
Adverum Biotechnologies, Inc.
Outcome results
None listed