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

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

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.

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: GB-102; Drug: Aflibercept

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85296
      • Retinal Consultants of Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • New York
    • Lynbrook, New York, United States, 11563
      • Ophthalmic Consultants of Long Island
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Research Center, PLLC
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: GB-102; Intravitreal injection of GB-102; Other Names: Sunitinib malate
EXPERIMENTAL: Experimental: Phase 2 - GB-102; Low dose or high dose injected every 6 months	Drug: GB-102; Intravitreal injection of GB-102; Other Names: Sunitinib malate
ACTIVE_COMPARATOR: Active Comparator: Phase 2 - Aflibercept; Aflibercept 2 mg injected every 2 months	Drug: Aflibercept; Intravitreal injection of Aflibercept.; Other Names: Anti-VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Occurrence of ocular and nonocular adverse events (AEs)	Number of adverse events in total and number of subjects with an adverse event	8 months
Phase 2: Change from baseline in best corrected visual acuity by ETDRS	Mean change from Baseline at Day 270 (Month 9) in best corrected visual acuity (BCVA) measured by early treatment diabetic retinopathy (ETDRS)	Baseline, Month 9

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Graybug Vision
• Investigators: Study Director: Charles P. Semba, MD, Graybug Vision, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 29, 2017
• Primary Completion (ACTUAL): September 13, 2018
• Study Completion (ACTUAL): January 16, 2019

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (ACTUAL): August 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Age-related macular degeneration; Choroidal neovascularization
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Aflibercept
• Other Study ID Numbers: GBV-102-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No