Neovascular Age-Related Macular Degeneration (nAMD), Wet AMD
Conditions
Keywords
Ixoberogene soroparvovec, Ixo-vec, Aflibercept, Neovascular age-related macular degeneration, nAMD, ADVM, ADVM-022, Wet AMD, wAMD, Wet Age-related Macular Degeneration, CNV, Neovascular AMD, AAV, AAV vector, AAV.7m8-aflibercept, AAV.7m8, Gene therapy, Eye disease, Blindness, Adeno-associated viruses, ADVM-022-13
Brief summary
This is a multi-center, randomized, double-masked, active-comparator-controlled, Phase 3 study in a broad participant population (treatment-naïve and treatment-experienced) with neovascular (wet) age-related macular degeneration (nAMD). The study will evaluate a single intravitreal (IVT) injection of Ixo-vec compared to intravitreal aflibercept (active comparator). The primary endpoint of this study is the mean change in best corrected visual acuity (BCVA) of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56. Safety, tolerability, and efficacy will be evaluated throughout the study.
Detailed description
The primary objective of this study is to evaluate the non-inferiority in efficacy of a single IVT injection of Ixo-vec 6 x 10\^10 vector genome (vg)/eye compared to an active comparator. Non-inferiority will be evaluated using a pre-specified margin defined in the protocol. Neovascular AMD is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent IVT injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. Ixo-vec (also known as ADVM-022 or AAV.7m8-aflibercept) is an adeno-associated virus (AAV)-based gene therapy product being developed for the treatment of nAMD. Ixo-vec is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice. Safety, tolerability, and efficacy will be evaluated throughout this study. The primary endpoint of this study is the mean change in BCVA of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56 post-treatment. Due to the long duration of the Screening period, this study will be considered fully enrolled when randomization has been completed.
Interventions
GENETICIxo-vec
Ixo-vec will be administered intravitreally.
DRUGAflibercept
Aflibercept will be administered intravitreally.
Sponsors
Adverum Biotechnologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able and willing to provide informed consent (or have a legally authorized representative who is able and willing to provide informed consent) prior to any study assessments and procedures and comply with the study requirements and visits. 2. Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity at Screening Visit 1. 3. At least 50 years old at Screening Visit 1. 4. An ETDRS BCVA letter score of 35 - 78 (approximate Snellen equivalent of 20/200 to 20/32) in the study eye at Screening Visit 1. 5. Demonstrated a meaningful anatomic response to anti-VEGF therapy during screening. 6. Able to reliably use eye drops per protocol.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change from Baseline in BCVA Based on an Average at Weeks 52 and 56 | Baseline, Week 52 and Week 56 | BCVA will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Aflibercept IVT Injections Received | Week 4 through Week 56 | — |
| Percentage of Participants with Worsened BCVA | Through Week 56 | BCVA measured by ETDRS. |
| Percentage of Participants with Improved BCVA | Through Week 56 | BCVA measured by ETDRS. |
| Mean Change from Baseline in BCVA Over Time Based on an Average at Weeks 52 and 56 | Baseline Through Week 56 | BCVA measured by ETDRS. |
| Mean Change from Week 1 in BCVA Based on an Average at Weeks 52 and 56 | Week 1 through Week 56 | BCVA measured by ETDRS. |
| Percentage of Participants with BCVA of 73 Letters or More from Week 4 Through Week 56 | Week 4 through Week 56 | — |
| Mean Change in Central Subfield Thickness (CST) from Baseline Over Time Through Week 56 | Baseline Through Week 56 | CST as measured by spectral domain optical coherence tomography (SD-OCT). |
| Percentage of Participants with CST ≤ 300 μm Over Time Through Week 56 | Through Week 56 | CST will be assessed by a central reading center (CRC) using SD-OCT. |
| Mean Number of CST Fluctuations > 50 μm From Week 1 Over Time Through Week 56 | Week 1 through Week 56 | CST will be assessed by a CRC using SD-OCT images and the mean number of fluctuations with thickness of more than 50 μm will be summarized. |
| Percentage of Participants with CST Fluctuations > 50 μm from Week 1 Over Time Through Week 56 | Week 1 through Week 56 | CST will be assessed using SD-OCT. |
| Percent Reduction in Mean Rate of Annualized Anti-VEGF Injections | Through Week 56 | Percent reduction in mean rate of annualized anti-VEGF injections will be assessed relative to the reduction in mean rate of annualized anti-VEGF injections received in the year prior to screening in treatment-experienced participants. |
| Percentage of Participants Who Were Aflibercept Injection-free | Week 4 through Week 56 | — |
| Percentage of Participants Who Received 0 or 1 Aflibercept Injection | Week 4 through Week 56 | — |
| Mean Change in Area of Choroidal Neovascularization (CNV) Lesion from Baseline Over Time Through Week 56 | Baseline through Week 56 | CNV is the infiltration of abnormal blood vessels in the retina from the underlying choroid layer. It will be assessed by a CRC using SD-OCT. |
| Mean Change in Macular Volume from Baseline Over Time Through Week 56 | Baseline through Week 56 | Macular volume will be measured as part of the full ophthalmic examination. |
| Percentage of Participants Without Intraretinal Fluid (IRF) Over Time Through Week 56 | Through Week 56 | IRF will be assessed using SD-OCT. |
| Percentage of Participants Without Subretinal Fluid (SRF) Over Time Through Week 56 | Through Week 56 | SRF will be assessed using SD-OCT. |
| Percentage of Participants Without IRF and/or SRF Over Time Through Week 56 | Through Week 56 | IRF and SRF will be assessed using SD-OCT. |
| Time to Dry Retina | Through Week 56 | Dry retina is defined as no IRF or SRF (i.e., absence of both). IRF and SRF will be assessed using SD-OCT. |
| Time to Sustained Dry Retina | Through Week 56 | Sustained dry retina is defined as no IRF or SRF (i.e., absence of both) maintained for 2 consecutive visits. |
| Number of Participants Who Experienced Ocular Adverse Events | Through Week 56 | The number of participants who experience an ocular adverse event will be summarized. |
| Number of Participants Who Experienced Mild, Moderate or Severe Ocular Adverse Events | Through Week 56 | The number of participants who experience a mild, moderate or severe ocular adverse event will be summarized. |
| Number of Participants Who Experienced Non-ocular Adverse Events | Through Week 56 | The number of participants who experience a non-ocular adverse event will be summarized. |
| Number of Participants Who Experienced Mild, Moderate or Severe Non-ocular Adverse Events | Through Week 56 | The number of participants who experience a mild, moderate or severe non-ocular adverse event will be summarized. |
| Mean Change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Total and Subscale Scores | Day 1 to Week 28 and Week 56 | The NEI VFQ-25 measures vision-targeted patient-reported outcomes of individuals with chronic eye diseases. It comprises 25 questions. The assessment generates an overall composite score and includes the following subscales: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social functioning due to vision, role limitations due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral and color vision, and ocular pain. A decrease in the NEI VFQ-25 score represents an improvement in disease severity. |
| Mean Change in the 5-item Health-related Quality of Life Questionnaire (EQ-5D-5L) | Day 1 to Week 28 and Week 56 | The EQ-5D-5L is a concise, generic self-reported health questionnaire which is weighted to reflect the relevant importance to patients of various different health problems. In retinal disease, the questionnaire is used to assess quality of life in the context of vision loss. It measures five parameters; mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the EQ-5D-5L score represents an improvement in disease severity. |
Countries
United States
Contacts
CONTACTAdverum Study Contact
STUDY_DIRECTORAdam Turpcu, PhD
Adverum Biotechnologies, Inc.
Outcome results
None listed