Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment. Substudies will evaluate the safety and tolerability of 4D-150 contralateral eye dosing and characterize vector shedding.
This Phase 1/2 trial is a prospective, multicenter, Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment who have demonstrated a clinical response consistent with anti-VEGF activity. The trial consists of Dose Escalation, Dose Expansion, Steroid Optimization, and\[DD1.1\]\[JA1.2\] Population Extension Cohorts. After receiving one time administration of 4D-150 by intravitreal injection (IVT), subjects will undergo assessments at monthly intervals for 24 months to assess safety and efficacy outcomes. Only subjects that received 4D-150 will then enter a long-term follow-up (LTFU) period to assess long-term safety of 4D-150 gene therapy and duration of clinical activity through year 5 (60 months). Eligible subjects who received 4D-150 in the study eye may participate in a sub-study to evaluate one-time IVT administration of 4D-150 to the contralateral ("fellow") eye. Additional subjects will be enrolled in a separate sub-study to characterize the vector shedding profile of one-time administration of IVT 4D-150. In both sub-studies, subjects will undergo regular assessments to assess safety and tolerability through Week 52 and then will enter long-term follow-up for safety evaluation through year 5 (60 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
215
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept
Commercially available Active Comparator Other Name: Eylea
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters
Time frame: 52 weeks
Time to receiving the first supplemental aflibercept injection
Time frame: 52 weeks
Percentage of subjects requiring supplemental aflibercept injections over 52 weeks
Time frame: 52 weeks
Number of supplemental aflibercept injections over 52 weeks
Time frame: 52 weeks
Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart
Time frame: 52 weeks
Change from baseline in central subfield thickness (CST) over time (up to 52 weeks) measured by spectral domain optical coherence tomography (SD-OCT)
Time frame: 52 weeks
Percent Change in Annualized Mean Number of anti-VEGF IVT injections before and after the 4D-150 injection
Percent change in annualized mean number of anti-VEGF IVT injections before and after the 4D-150 injection (or Day 1 for the aflibercept only arm)
Time frame: Before and after the 4D-150 injection (or Day 1 for the aflibercept only arm)
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