A Depot Formulation of Sunitinib Malate (GB-102) in Subjects With Neovascular (Wet) Age-related Macular Degeneration

Phase 1

Completed

• Conditions: Neovascular Age-Related Macular Degeneration
• Interventions: Drug: GB-102; Drug: Aflibercept

• Registration Number: NCT03249740
• Lead Sponsor: Graybug Vision

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.

Study Timeline

• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-08-10
• Study First Posted: 2017-08-15
• Study Start: 2017-08-29
• Primary Completion: 2018-09-13
• Study Completion: 2019-01-16
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-18
• Last Update Posted: 2019-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Males or females of any race, ≥ 50 years of age
2. 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)
3. Evidence of increased vascular permeability and/or loss of visual acuity

Key

Exclusion Criteria

1. 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
2. Uncontrolled hypertension, diabetes mellitus, IOP, hypothyroidism, or hyperthyroidism
3. Chronic renal disease
4. Abnormal liver function
5. Women who are pregnant or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: Phase 1 - GB-102	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.
Experimental: Phase 2 - GB-102	GB-102	Low dose or high dose injected every 6 months
Active Comparator: Phase 2 - Aflibercept	Aflibercept	Aflibercept 2 mg injected every 2 months

Primary Outcome Measures

Name	Time	Method
Phase 1: Occurrence of ocular and nonocular adverse events (AEs)	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	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 Outcome Measures

Name	Time	Method
Phase 1: Systemic exposure to sunitinib measured in plasma level	8 months	Plasma levels of sunitinib (ng/mL)
Phase 2: Proportion of subjects with < 15 BCVA letter loss by ETDRS	12 months	Proportion of subjects with \< 15 letters lost in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12
Phase 2: Proportion of subjects with ≥ 15 BCVA letters gained by ETDRS	12 months	Proportion of subjects with ≥ 15 letters gained in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12
Phase 2: Change from baseline in BCVA by ETDRS	12 months	Mean change from baseline in mean BCVA measured by early treatment
Phase 1: Change from baseline in BCVA by ETDRS	8 months	Mean change from baseline in mean BCVA measured by early treatment diabetic retinopathy (ETDRS) method
Phase 2: Occurrence of ocular and nonocular adverse events (AEs)	12 months	Number of adverse events in total and number of subjects with an adverse event
Phase 2: Systemic exposure to sunitinib measured in plasma level	12 months	Plasma levels of sunitinib (ng/mL)
Phase 2: Change from baseline in sub-retinal thickness	12 months	Mean change from baseline in sub-retinal thickness (microns) by SD-OCT
Phase 2: Rescue medication	12 months	Proportion of subjects receiving rescue medication and median time to rescue medication
Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT	12 months	Assessment of retinal fluid by SD-OCT
Phase 1: Change from baseline in sub-retinal thickness	8 months	Mean change from baseline in sub-retinal thickness (microns) by spectral domain - optical coherence tomography (SD-OCT)
Phase 1: Change from baseline in retinal fluid by SD-OCT	8 months	Assessment of retinal fluid by SD-OCT
Phase 1: Change from baseline in total lesion area by FA/CFP	8 months	Lesion area (total) by fluorescein angiography/color fundus photography (FA/CFP)
Phase 1: Change from baseline in CNV lesion area by FA/CFP	8 months	CNV lesion area by FA/CFP
Phase 1: Rescue medication	8 months	Proportion of subjects receiving rescue medication and median time to rescue medication
Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height	8 months	Subretinal hyper reflective material (SHRM) height
Phase 1: Change from baseline in fluorescein leakage area by FA/CFP	8 months	Area of fluorescein leakage by FA/CFP

Trial Locations

Locations (8)

Midwest Eye Institute; 🇺🇸 Indianapolis, Indiana, United States

Retina Research Center, PLLC; 🇺🇸 Austin, Texas, United States

Retinal Consultants of Arizona; 🇺🇸 Gilbert, Arizona, United States

Retina-Vitreous Associates Medical Group; 🇺🇸 Beverly Hills, California, United States

Texas Retina Associates; 🇺🇸 Arlington, Texas, United States

Medical Center Ophthalmology Associates; 🇺🇸 San Antonio, Texas, United States

Ophthalmic Consultants of Long Island; 🇺🇸 Lynbrook, New York, United States

Retina Research Institute of Texas; 🇺🇸 Abilene, Texas, United States