Diabetic Macular Edema, Diabetic Retinopathy
Conditions
Keywords
Retinal gene therapy, Intravitreal gene therapy, DME, SPECTRA
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.
Interventions
BIOLOGICAL4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
BIOLOGICALAflibercept IVT
Commercially available Active Comparator
Sponsors
4D Molecular Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
No masking in Dose Confirmation (Part 1). In Dose Expansion (Part 2), participants and outcomes assessors will be masked to the treatment arm for the duration of the trial.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * CST ≥ 350 μm (Spectralis SD-OCT) in the study eye at Screening, confirmed by the independent reading center * 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1) | 60 months |
| Annualized number of aflibercept injections in the study eye (Part 2) | 52 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Mean cumulative number of aflibercept injections over time | 52 weeks |
| Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart at Weeks 52 and 104 | 104 weeks |
| Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) at Weeks 104 | 104 weeks |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORJulie Clark, MD
4D Molecular Therapeutics
Outcome results
None listed