Clinical trial NCT05197270: 4D-150 in Patients with Neovascular (Wet) Age-Related Macular Degeneration
Official title: A Phase 1/2 Dose-Escalation and Randomized, Controlled, Masked Expansion Trial of Intravitreal 4D-150 Gene Therapy in Adults with Neovascular (Wet) Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neovascular (Wet) Age-Related Macular Degeneration
Keywords: Age-related macular degeneration
AMD
Exudative AMD
Exudative age-related macular degeneration
Neovascular AMD
Neovascular age-related macular degeneration
Wet age-related macular degeneration
Wet macular degeneration
Wet AMD
wAMD
Retinal gene therapy
Intravitreal gene therapy
Genetic Medicine
Ocular Gene Therapy
Lead sponsor: 4D Molecular Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-01-19
Enrollment: 215
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: In Dose Escalation, the safety and tolerability of multiple dose levels of 4D-150 will be examined following an open-label, 3+3 dose escalation design (n=3-5 per dose level). In Dose Expansion, subjects (n=50) will be randomized to receive one of 2 dose levels of 4D-150 (n=20 for each dose level) based on results from Dose Escalation, or aflibercept (n=10). In Steroid Optimization (n=up to 96) and Population Extension (n=up to 45) Cohorts, subjects will be assigned sequentially to receive 4D-150 at doses cleared by the DSMC.
Primary purpose: TREATMENT

Brief summary: Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment

Detailed description: 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 Population Extension Cohorts.

After receiving one time administration of 4D-150 by intravitreal injection, 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).

Eligibility criteria: Inclusion Criteria:

* ≥50 years of age
* Diagnosed with macular CNV secondary to AMD
* BCVA ETDRS Snellen equivalent for dose escalation between \~20/32 and \~20/320, or for dose expansion and population extension between \~20/25 and\~20/200, for steroid optimization between \~20/25 and \~20/640
* Currently receiving anti-VEGF treatment in the study eye and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening

Exclusion Criteria:

* Any condition preventing visual acuity improvement in the study eye
* Prior treatment with photodynamic therapy or retinal laser in the study eye
* History of uveitis in either eye
* Any other pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters
timeFrame: 52 weeks
Secondary outcomes:
measure: Time to receiving the first supplemental aflibercept injection
timeFrame: 52 weeks
measure: Percentage of subjects requiring supplemental aflibercept injections over 52 weeks
timeFrame: 52 weeks
measure: Number of supplemental aflibercept injections over 52 weeks
timeFrame: 52 weeks
measure: Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart
timeFrame: 52 weeks
measure: Change from baseline in central subfield thickness (CST) over time (up to 52 weeks) measured by spectral domain optical coherence tomography (SD-OCT)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barnet Delaney Perkins Eye Center
state: Arizona
city: Oxnard
country: United States
facility: California Retina Consultants
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Lakewood
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Deerfield Beach
country: United States
facility: Rand Eye Institute
state: Florida
city: Gainesville
country: United States
facility: Vitreo Retinal Associates
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Pensacola
country: United States
facility: Retinal Specialty Institute
state: Florida
city: Tampa
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Oak Forest
country: United States
facility: University Retina and Macula Associates
state: Illinois
city: Carmel
country: United States
facility: Retina Partners Midwest
state: Indiana
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston & Boston Eye Surgery and Laser Center
state: Massachusetts
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Asheville
country: United States
facility: Western Carolina Retinal Associates
state: North Carolina
city: Eugene
country: United States
facility: Verum Research, LLC
state: Oregon
city: Bethlehem
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center, LLC
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Retina
state: Tennessee
city: Austin
country: United States
facility: Austin Clinical Research
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, PA
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Bellevue
country: United States
facility: Pacific Northwest Retina LLC
state: Washington
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center, LLC
Study officials:
affiliation: 4D Molecular Therapeutics
name: Jennifer Lee, MD
role: STUDY_DIRECTOR
References: