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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Neovascular Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: GB-102
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Phase 1 - GB-102<br>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<br>* Intravitreal injection of GB-102<br>* Other names: Sunitinib malate;|
| Experimental: Experimental: Phase 2 - GB-102<br>Low dose or high dose injected every 6 months | Drug: GB-102<br>* Intravitreal injection of GB-102<br>* Other names: Sunitinib malate;|
| Active Comparator: Active Comparator: Phase 2 - Aflibercept<br>Aflibercept 2 mg injected every 2 months | Drug: Aflibercept<br>* Intravitreal injection of Aflibercept.<br>* Other names: Anti-VEGF;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related macular degeneration, Choroidal neovascularization