Clinical trial NCT05930561: 4D-150 in Patients With Diabetic Macular Edema
Official title: A Phase 2 Randomized, Active-Controlled, Double-masked Trial of Intravitreal 4D-150 Gene Therapy in Adults With Diabetic Macular Edema (SPECTRA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Macular Edema
Diabetic Retinopathy
Keywords: Retinal gene therapy
Intravitreal gene therapy
DME
SPECTRA
Lead sponsor: 4D Molecular Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-05
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In Dose Confirmation (Part 1), subjects (n=12-18) will be sequentially assigned to one of two open-label dose levels of 4D-150 (n=6-9 per dose level). In Dose Expansion (Part 2), subjects (n=54) will be randomized to receive one of two dose levels of 4D-150 (n=18 per dose level) based on results from Dose Confirmation, or aflibercept control (n=18). Subjects will be masked to treatment arm in Dose Expansion (Part 2).
Primary purpose: TREATMENT

Brief summary: Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).

Detailed description: This Phase 2 trial is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of 4D-150 in adults with DME. The trial will be conducted in two parts: Dose Confirmation and Dose Expansion.

Eligibility criteria: Inclusion Criteria:

* ≥18 years of age
* Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening
* Demonstrate clinical response to on-study aflibercept injection in the study eye.
* Decreased visual acuity attributable primarily to DME
* BCVA in the study eye between 25 and 83 ETDRS letters, inclusive (\~20/320 and 20/25, respectively) at Screening
* Study eye amenable to IVT injection
* Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures
* Provide written informed consent

Exclusion Criteria:

* Macular edema in the study eye considered to be secondary to a cause other than DME
* Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation
* Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months
* Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1)
* Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye
* Any concurrent ocular condition in the study eye that is likely to require surgical intervention (e.g. cataract surgery) during the 2 year (104 week) study duration

Note: Other inclusion/exclusion criteria apply.

Primary outcomes:
measure: Annualized number of aflibercept injections in the study eye
timeFrame: 52 weeks
Secondary outcomes:
measure: Mean cumulative number of aflibercept injections over time
timeFrame: 52 weeks
measure: Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart
timeFrame: 104 weeks
measure: Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT)
timeFrame: 104 weeks
measure: Percentage of subjects with a ≥2 and ≥3-Step Diabetic Retinopathy Severity (DRS) improvement from baseline on the ETDRS-DRSS
timeFrame: 104 weeks
Other outcomes:
measure: Incidence and severity of treatment-emergent adverse events and serious adverse events, including clinically significant changes in safety parameters
timeFrame: 104 weeks
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute LLC
state: Arizona
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado
state: Colorado
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Carmel
country: United States
facility: Raj K Maturi MD PC
state: Indiana
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Albuquerque
country: United States
facility: Vision Research Center Eye Associates of New Mexico
state: New Mexico
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: Erie
country: United States
facility: Erie Retina Research
state: Pennsylvania
city: Austin
country: United States
facility: Austin Clinical Research
state: Texas
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center
Study officials:
affiliation: 4D Molecular Therapeutics
name: Schonmei Lee, MD
role: STUDY_DIRECTOR
References: