ADVM-022 Intravitreal Gene Therapy for Wet AMD (OPTIC)

• ClinicalTrials.gov Identifier: NCT03748784
• Recruitment Status: Completed
• First Posted: November 21, 2018
• Last Update Posted: August 8, 2023
• Sponsor: Adverum Biotechnologies, Inc.
• Information provided by (Responsible Party): Adverum Biotechnologies, Inc.

Tracking Information

• First Submitted Date: November 19, 2018
• First Posted Date: November 21, 2018
• Last Update Posted Date: August 8, 2023
• Actual Study Start Date: November 14, 2018
• Actual Primary Completion Date: June 22, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2019)

Type, severity, and incidence of ocular and systemic adverse events (AEs) [ Time Frame: 104 weeks ]

Type, severity, and incidence of ocular and systemic adverse events (AEs)

Original Primary Outcome Measures (submitted: November 19, 2018)

Type, severity, and incidence of ocular and systemic adverse events (AEs) [ Time Frame: 24 weeks ]

Type, severity, and incidence of ocular and systemic adverse events (AEs)

Current Secondary Outcome Measures (submitted: October 11, 2019)

• Change in best corrected visual acuity (BCVA) [ Time Frame: 104 weeks ]
  Change in best corrected visual acuity (BCVA)
• Change in central subfield thickness (CST) and macular volume measured by SD-OCT [ Time Frame: 104 weeks ]
  Change in central subfield thickness (CST) and macular volume measured by SD-OCT
• Percentage of subjects requiring anti-VEGF injections over time [ Time Frame: 104 weeks ]
  Percentage of subjects requiring anti-VEGF injections over time
• Mean number of anti-VEGF injections over time [ Time Frame: 104 weeks ]
  Mean number of anti-VEGF injections over time
• Percentage of subjects without intraretinal fluid over time [ Time Frame: 104 weeks ]
  Percentage of subjects without intraretinal fluid over time
• Percentage of subjects without subretinal fluid over time [ Time Frame: 104 weeks ]
  Percentage of subjects without subretinal fluid over time

Original Secondary Outcome Measures (submitted: November 19, 2018)

• Change in best corrected visual acuity (BCVA) [ Time Frame: 24 weeks ]
  Change in best corrected visual acuity (BCVA)
• Change in central retinal thickness (CRT measured by SD-OCT) [ Time Frame: 24 weeks ]
  Change in central retinal thickness (CRT measured by SD-OCT)
• Percentage of subjects requiring anti-VEGF injections through 104 weeks [ Time Frame: 104 weeks ]
  Percentage of subjects requiring anti-VEGF injections through 104 weeks
• Mean number of anti-VEGF injections through 104 weeks [ Time Frame: 104 weeks ]
  Mean number of anti-VEGF injections through 104 weeks

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ADVM-022 Intravitreal Gene Therapy for Wet AMD
• Official Title: An Open Label Phase 1 Study of ADVM-022 (AAV.7m8-aflibercept) in Neovascular (Wet) Age-Related Macular Degeneration
• 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment

Condition

• Wet Age-related Macular Degeneration
• Neovascular Age-related Macular Degeneration

Intervention

Biological: ADVM-022

ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept

Other Name: AAV.7m8-aflibercept

Study Arms

• Experimental: Dose 1
  6E11 vg of ADVM-022
  Intervention: Biological: ADVM-022
• Experimental: Dose 2
  2E11 vg of ADVM-022
  Intervention: Biological: ADVM-022

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 11, 2019): 30
• Original Estimated Enrollment (submitted: November 19, 2018): 18
• Actual Study Completion Date: June 22, 2022
• Actual Primary Completion Date: June 22, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03748784
• Other Study ID Numbers: ADVM-022-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Adverum Biotechnologies, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Adverum Biotechnologies, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: OPTIC Medical Monitor; Adverum Biotechnologies, Inc.

• PRS Account: Adverum Biotechnologies, Inc.
• Verification Date: August 2023