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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Outcomes Assessor)
  • Study Primary Completion Date: September 13, 2018

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.

Interventions

  • Drug: GB-102
    • Intravitreal injection of GB-102
  • Drug: Aflibercept
    • Intravitreal injection of Aflibercept.

Arms, Groups and Cohorts

  • 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.
  • Experimental: Experimental: Phase 2 – GB-102
    • Low dose or high dose injected every 6 months
  • Active Comparator: Active Comparator: Phase 2 – Aflibercept
    • Aflibercept 2 mg injected every 2 months

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • Phase 1: Change from baseline in BCVA by ETDRS
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 8 months
    • Assessment of retinal fluid by SD-OCT
  • Phase 1: Change from baseline in total lesion area by FA/CFP
    • Time Frame: 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
    • Time Frame: 8 months
    • CNV lesion area by FA/CFP
  • Phase 1: Change from baseline in fluorescein leakage area by FA/CFP
    • Time Frame: 8 months
    • Area of fluorescein leakage by FA/CFP
  • Phase 1: Rescue medication
    • Time Frame: 8 months
    • Proportion of subjects receiving rescue medication and median time to rescue medication
  • Phase 1: Systemic exposure to sunitinib measured in plasma level
    • Time Frame: 8 months
    • Plasma levels of sunitinib (ng/mL)
  • Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height
    • Time Frame: 8 months
    • Subretinal hyper reflective material (SHRM) height
  • Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT
    • Time Frame: 12 months
    • Assessment of retinal fluid by SD-OCT
  • Phase 2: Proportion of subjects with < 15 BCVA letter loss by ETDRS
    • Time Frame: 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
    • Time Frame: 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)
    • Time Frame: 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
    • Time Frame: 12 months
    • Mean change from baseline in mean BCVA measured by early treatment
  • Phase 2: Systemic exposure to sunitinib measured in plasma level
    • Time Frame: 12 months
    • Plasma levels of sunitinib (ng/mL)
  • Phase 2: Change from baseline in sub-retinal thickness
    • Time Frame: 12 months
    • Mean change from baseline in sub-retinal thickness (microns) by SD-OCT
  • Phase 2: Rescue medication
    • Time Frame: 12 months
    • Proportion of subjects receiving rescue medication and median time to rescue medication

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Graybug Vision
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Charles P. Semba, MD, Study Director, Graybug Vision, Inc.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.