A Phase 1/2 Multicenter Study Evaluating the Safety, Tolerability, and Efficacy of an Intravitreal Depot Formulation of Sunitinib Malate (GB-102) in Subjects With Neovascular Age-related Macular Degeneration
Overview
- Phase
- Phase 1
- Intervention
- GB-102
- Conditions
- Neovascular Age-Related Macular Degeneration
- Sponsor
- Graybug Vision
- Enrollment
- 32
- Locations
- 8
- Primary Endpoint
- Phase 1: Occurrence of ocular and nonocular adverse events (AEs)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of single and repeated intravitreal injections of GB-102 in subjects with neovascular (wet) age-related macular degeneration.
Detailed Description
In this 2-part study, Part 1 is a multicenter, open-label, safety, tolerability, and systemic exposure evaluation to Sunitinib in escalating doses of a single IVT injection of GB-102, while Part 2 is a multicenter, double-masked, randomized (1:1:1), parallel-group, safety, and efficacy evaluation of repeated IVT injections of 2 dose levels of GB-102 compared with aflibercept.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or females of any race, ≥ 50 years of age
- •Presence of an active CNV lesion secondary to AMD treated with at least 3 monthly injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab)
- •Evidence of increased vascular permeability and/or loss of visual acuity
Exclusion Criteria
- •History, within 6 months prior to screening, of any of the following: myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke
- •Uncontrolled hypertension, diabetes mellitus, IOP, hypothyroidism, or hyperthyroidism
- •Chronic renal disease
- •Abnormal liver function
- •Women who are pregnant or lactating
Arms & Interventions
Experimental: Phase 1 - GB-102
Subjects will be assigned to 1 of 4 cohorts to receive a single intravitreal injection of up to 2.0 mg (50 μL) GB-102.
Intervention: GB-102
Experimental: Phase 2 - GB-102
Low dose or high dose injected every 6 months
Intervention: GB-102
Active Comparator: Phase 2 - Aflibercept
Aflibercept 2 mg injected every 2 months
Intervention: Aflibercept
Outcomes
Primary Outcomes
Phase 1: Occurrence of ocular and nonocular adverse events (AEs)
Time Frame: 8 months
Number of adverse events in total and number of subjects with an adverse event
Phase 2: Change from baseline in best corrected visual acuity by ETDRS
Time Frame: Baseline, Month 9
Mean change from Baseline at Day 270 (Month 9) in best corrected visual acuity (BCVA) measured by early treatment diabetic retinopathy (ETDRS)
Secondary Outcomes
- Phase 1: Systemic exposure to sunitinib measured in plasma level(8 months)
- Phase 2: Proportion of subjects with < 15 BCVA letter loss by ETDRS(12 months)
- Phase 2: Proportion of subjects with ≥ 15 BCVA letters gained by ETDRS(12 months)
- Phase 2: Change from baseline in BCVA by ETDRS(12 months)
- Phase 1: Change from baseline in BCVA by ETDRS(8 months)
- Phase 2: Occurrence of ocular and nonocular adverse events (AEs)(12 months)
- Phase 2: Systemic exposure to sunitinib measured in plasma level(12 months)
- Phase 2: Change from baseline in sub-retinal thickness(12 months)
- Phase 2: Rescue medication(12 months)
- Phase 1: Change from baseline in sub-retinal thickness(8 months)
- Phase 1: Change from baseline in retinal fluid by SD-OCT(8 months)
- Phase 1: Change from baseline in total lesion area by FA/CFP(8 months)
- Phase 1: Change from baseline in CNV lesion area by FA/CFP(8 months)
- Phase 1: Rescue medication(8 months)
- Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height(8 months)
- Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT(12 months)
- Phase 1: Change from baseline in fluorescein leakage area by FA/CFP(8 months)