ADVM-022 Intravitreal Gene Therapy for Wet AMD (OPTIC)
Primary Purpose
Wet Age-related Macular Degeneration, Neovascular Age-related Macular Degeneration
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ADVM-022
Sponsored by
About this trial
This is an interventional treatment trial for Wet Age-related Macular Degeneration focused on measuring Choroidal Neovascularizatio, ADVM-022, CNV, ADVM-022-01, AAV.7m8, Anti-VEGF therapy, Blindness, Gene therapy, Aflibercept (Eylea), Age-Related Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, AAV Vector, Adverum, wAMD, AMD, wet AMD
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 50
- Diagnosis of neovascular (wet) AMD
- BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320 for each cohort
- Subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening
- Demonstrated a meaningful response to anti-VEGF therapy
- Willing and able to provide consent
Exclusion Criteria:
- History of retinal disease in the study eye other than wet AMD
- Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement
- History of retinal detachment (with or without repair) in the study eye
- History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye
- Uncontrolled glaucoma in the study eye
- Any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye
- Any previous intraocular or periocular surgery on the study eye within 6 months
- Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months
- Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg
Sites / Locations
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
- Adverum Clinical Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose 1
Dose 2
Arm Description
6E11 vg of ADVM-022
2E11 vg of ADVM-022
Outcomes
Primary Outcome Measures
Type, severity, and incidence of ocular and systemic adverse events (AEs)
Type, severity, and incidence of ocular and systemic adverse events (AEs)
Secondary Outcome Measures
Change in best corrected visual acuity (BCVA)
Change in best corrected visual acuity (BCVA)
Change in central subfield thickness (CST) and macular volume measured by SD-OCT
Change in central subfield thickness (CST) and macular volume measured by SD-OCT
Percentage of subjects requiring anti-VEGF injections over time
Percentage of subjects requiring anti-VEGF injections over time
Mean number of anti-VEGF injections over time
Mean number of anti-VEGF injections over time
Percentage of subjects without intraretinal fluid over time
Percentage of subjects without intraretinal fluid over time
Percentage of subjects without subretinal fluid over time
Percentage of subjects without subretinal fluid over time
Full Information
NCT ID
NCT03748784
First Posted
November 19, 2018
Last Updated
August 4, 2023
Sponsor
Adverum Biotechnologies, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03748784
Brief Title
ADVM-022 Intravitreal Gene Therapy for Wet AMD
Acronym
OPTIC
Official Title
An Open Label Phase 1 Study of ADVM-022 (AAV.7m8-aflibercept) in Neovascular (Wet) Age-Related Macular Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 14, 2018 (Actual)
Primary Completion Date
June 22, 2022 (Actual)
Study Completion Date
June 22, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adverum Biotechnologies, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition and the leading cause of blindness in the elderly. The available therapies for treating wet AMD require life-long intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A one-time IVT administration of ADVM-022 has the potential to treat wet AMD by providing durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and maintaining the vision of patients. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with wet AMD receiving anti-VEGF therapy in clinical practice.
Detailed Description
This open-label, multicenter, dose-ranging study will evaluate 2 dose levels in up to 30 subjects (15 per dose) with active choroidal neovascularization (CNV) secondary to AMD. Subjects who are under active anti-VEGF treatment and have demonstrated a meaningful response to anti-VEGF therapy will be considered for participation in this study. The primary endpoint for this study is safety and tolerability of ADVM-022. All subjects will continue to be assessed for 104 weeks following treatment with ADVM-022.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wet Age-related Macular Degeneration, Neovascular Age-related Macular Degeneration
Keywords
Choroidal Neovascularizatio, ADVM-022, CNV, ADVM-022-01, AAV.7m8, Anti-VEGF therapy, Blindness, Gene therapy, Aflibercept (Eylea), Age-Related Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, AAV Vector, Adverum, wAMD, AMD, wet AMD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose 1
Arm Type
Experimental
Arm Description
6E11 vg of ADVM-022
Arm Title
Dose 2
Arm Type
Experimental
Arm Description
2E11 vg of ADVM-022
Intervention Type
Biological
Intervention Name(s)
ADVM-022
Other Intervention Name(s)
AAV.7m8-aflibercept
Intervention Description
ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
Primary Outcome Measure Information:
Title
Type, severity, and incidence of ocular and systemic adverse events (AEs)
Description
Type, severity, and incidence of ocular and systemic adverse events (AEs)
Time Frame
104 weeks
Secondary Outcome Measure Information:
Title
Change in best corrected visual acuity (BCVA)
Description
Change in best corrected visual acuity (BCVA)
Time Frame
104 weeks
Title
Change in central subfield thickness (CST) and macular volume measured by SD-OCT
Description
Change in central subfield thickness (CST) and macular volume measured by SD-OCT
Time Frame
104 weeks
Title
Percentage of subjects requiring anti-VEGF injections over time
Description
Percentage of subjects requiring anti-VEGF injections over time
Time Frame
104 weeks
Title
Mean number of anti-VEGF injections over time
Description
Mean number of anti-VEGF injections over time
Time Frame
104 weeks
Title
Percentage of subjects without intraretinal fluid over time
Description
Percentage of subjects without intraretinal fluid over time
Time Frame
104 weeks
Title
Percentage of subjects without subretinal fluid over time
Description
Percentage of subjects without subretinal fluid over time
Time Frame
104 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 50
Diagnosis of neovascular (wet) AMD
BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320 for each cohort
Subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening
Demonstrated a meaningful response to anti-VEGF therapy
Willing and able to provide consent
Exclusion Criteria:
History of retinal disease in the study eye other than wet AMD
Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement
History of retinal detachment (with or without repair) in the study eye
History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye
Uncontrolled glaucoma in the study eye
Any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye
Any previous intraocular or periocular surgery on the study eye within 6 months
Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months
Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
OPTIC Medical Monitor
Organizational Affiliation
Adverum Biotechnologies, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Adverum Clinical Site
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Adverum Clinical Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Adverum Clinical Site
City
Golden
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
Adverum Clinical Site
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33064
Country
United States
Facility Name
Adverum Clinical Site
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Adverum Clinical Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Adverum Clinical Site
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Adverum Clinical Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Adverum Clinical Site
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Adverum Clinical Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Adverum Clinical Site
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77384
Country
United States
12. IPD Sharing Statement
Learn more about this trial
ADVM-022 Intravitreal Gene Therapy for Wet AMD
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