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

Sponsor

Graybug Vision (Industry)

Overall Status

Completed

CT.gov ID

NCT03249740

Collaborator

(none)

Enrollment

Locations

Arms

16.6

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-Related Macular Degeneration	Drug: GB-102 Drug: Aflibercept	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase 1: open-label GB-102 dose cohorts are initiated sequentially Phase 2: assignment to and initiation of cohorts occur in parallel - not completed in this study. Separate protocol (GBV-102-002) implemented for Phase 2.Phase 1: open-label GB-102 dose cohorts are initiated sequentially Phase 2: assignment to and initiation of cohorts occur in parallel - not completed in this study. Separate protocol (GBV-102-002) implemented for Phase 2.

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

Masking is relevant to Phase 2 only

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 29, 2017

Actual Primary Completion Date :

Sep 13, 2018

Actual Study Completion Date :

Jan 16, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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 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: Change from baseline in fluorescein leakage area by FA/CFP [8 months]
Area of fluorescein leakage by FA/CFP
Phase 1: Rescue medication [8 months]
Proportion of subjects receiving rescue medication and median time to rescue medication
Phase 1: Systemic exposure to sunitinib measured in plasma level [8 months]
Plasma levels of sunitinib (ng/mL)
Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height [8 months]
Subretinal hyper reflective material (SHRM) height
Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT [12 months]
Assessment of retinal fluid by SD-OCT
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: 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: Change from baseline in BCVA by ETDRS [12 months]
Mean change from baseline in mean BCVA measured by early treatment
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key 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

Key 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona	Gilbert	Arizona	United States	85296
2	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
3	Midwest Eye Institute	Indianapolis	Indiana	United States	46290
4	Ophthalmic Consultants of Long Island	Lynbrook	New York	United States	11563
5	Retina Research Institute of Texas	Abilene	Texas	United States	79606
6	Texas Retina Associates	Arlington	Texas	United States	76012
7	Retina Research Center, PLLC	Austin	Texas	United States	78705
8	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240