Diabetic Macular Edema (DME), Neovascular Age-related Macular Degeneration (nAMD), Retinal Vein Occlusion (RVO)
Conditions
Keywords
GenSci148, Diabetic Macular Edema, DME, Retinal Vein Occlusion, RVO, Intravitreal injection, Anti-VEGF, Angiopoietin-2, Neovascular Age-related Macular Degeneration, nAMD
Brief summary
This is a Phase I, multicenter, open-label, dose-escalation study conducted in two parts to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GenSci148 administered via intravitreal (IVT) injection in participants with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Part 1 evaluates single ascending doses in nAMD participants. Part 2 evaluates multiple doses in nAMD, DME, and RVO participants. The study also assesses immunogenicity and explores preliminary efficacy.
Detailed description
This is a Phase I, multicenter, open-label, dose-escalation study conducted in 2 parts to evaluate the safety, tolerability, PK and PD profiles, and immunogenicity, as well as the preliminary efficacy of intravitreal injection of GenSci148 in participants with nAMD, DME and RVO. Part 1 (Single Ascending Dose, SAD): Conducted in participants with nAMD. Four dose levels (1 mg/eye, 3 mg/eye, 7 mg/eye, and 10 mg/eye) are planned, administered via a single IVT injection. Dose escalation is determined by the Safety Review Committee (SRC) based on safety, tolerability, PK, PD, and other available data. Part 2 (Multiple Ascending Dose, MAD): Conducted in participants with nAMD, DME, and RVO. Three dose levels (low, medium, and high) are planned. Participants will receive multiple IVT injections according to the study schedule. Disease activity assessment will be performed during follow-up, and participants meeting retreatment criteria may receive additional doses of GenSci148. Safety assessments include adverse events, physical examinations, laboratory tests, vital signs, ECG, and ophthalmic examinations (BCVA, IOP, slit-lamp examination, , etc.). PK/PD and immunogenicity samples are collected at predefined time points.
Interventions
DRUGGenSci148 Injection
GenSci148 is a fusion protein that simultaneously targets VEGF-A, VEGF-C, VEGF-D, and Ang-2.
Sponsors
Changchun GeneScience Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. No masking is applied. Participants, investigators, and study staff are aware of the treatment assignment.
Intervention model description
Single-arm, open-label, dose-escalation study. Part 1 (SAD) evaluates 4 dose levels of single IVT injection of GenSci148 in nAMD participants. Part 2 (MAD) evaluates 3 dose levels of multiple IVT injections in nAMD, DME, and RVO participants. Dose escalation is determined by SRC based on safety and tolerability.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Able to understand the study and provide written informed consent prior to any study-related procedures. * Willing and able to comply with scheduled visits, treatment plan, and study procedures. * Best corrected visual acuity (BCVA) of 24 to 78 letters (inclusive) in the study eye, and BCVA ≥ 24 letters in the fellow eye.
Exclusion criteria
* Prior or current contraindicated ophthalmic treatments in study or fellow eye per protocol. * Refractive error \> ±8.0 diopters in the study eye. * Anterior segment neovascularization or vitreous hemorrhage in the study eye.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | 43 days(Part 1) and 40 weeks (Part 2) | TEAEs include ocular and systemic adverse events, graded by severity and relationship to study drug. Safety assessments include physical examination, vital signs, laboratory tests, ECG, and ophthalmic examinations. |
Countries
China
Contacts
CONTACTGaohui Zhou
Outcome results
None listed