A Depot Formulation of Sunitinib Malate (GB-102) Compared to Aflibercept in Subjects With Wet AMD (ALTISSIMO)

• ClinicalTrials.gov Identifier: NCT03953079
• Recruitment Status: Recruiting
• First Posted: May 16, 2019
• Last Update Posted: November 21, 2019
• Sponsor: Graybug Vision
• Information provided by (Responsible Party): Graybug Vision

Study Description

Brief Summary:

Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of repeated IVT injections of 3 dose levels of GB‑102 compared with aflibercept.

Condition or disease	Intervention/treatment	Phase
Neovascular Age-Related Macular Degeneration	Drug: Drug: GB-102; Drug: Aflibercept	Phase 2

Detailed Description:

Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of the effect of GB-102, as measured by time to first rescue treatment across multiple dose levels of GB-102 administered every 6 months as compared to intravitreal (IVT) aflibercept administered every 2 months in subjects with neovascular (wet) age-related macular degeneration who have received prior induction with anti-vascular endothelial growth factor (VEGF)

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel-arm design
• Masking: Single (Outcomes Assessor)
• Masking Description: Visual examiner-masked
• Primary Purpose: Treatment
• Official Title: A Phase 2b Multicenter Dose-Ranging Study Evaluating the Safety and Efficacy of Sunitinib Malate Depot Formulation (GB-102) Compared to Aflibercept in Subjects With Neovascular (Wet) Age-related Macular Degeneration (ALTISSIMO Study)
• Actual Study Start Date: September 26, 2019
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: GB-102 Dose 2 (1 mg); Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline and Month 6 and sham at Months 2, 4, 8 and 10.	Drug: Drug: GB-102; Intravitreal injection of GB-102; Other Name: Sunitinib malate
Experimental: GB-102 Dose 3 (2 mg); Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline and Month 6 and sham at Months 2, 4, 8 and 10.	Drug: Drug: GB-102; Intravitreal injection of GB-102; Other Name: Sunitinib malate
Active Comparator: Aflibercept 2 mg Dose; Participants will receive intravitreal (IVT) aflibercept 2 mg in the study eye at Baseline, Months 2, 4, 6, 8 and 10.	Drug: Aflibercept; Intravitreal injection of aflibercept (2 mg dose); Other Name: Eylea

Outcome Measures

Primary Outcome Measures :

1. Kaplan-Meier analyses of the proportion of treated subjects remaining rescue-free through Month 10 [ Time Frame: Baseline through 10 months ]
   Assessment of the percentage of subjects remaining rescue free at Month 10

Secondary Outcome Measures :

1. Mean change from baseline in best corrected visual acuity (BCVA) as assessed using the early treatment of diabetic retinopathy (ETDRS) protocol (range, 0 [worst] to 100 [best]) to the average BCVA ETDRS letter score at Months 9 and 10 [ Time Frame: Baseline through 10 months ]
   Assessment of change in BCVA from baseline compared to the average BCVA scores (ETDRS) at Months 9 and 10
2. Mean change from baseline in BCVA (ETDRS letter score) to all visits [ Time Frame: Baseline through 12 months ]

   BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy

   BCVA ETDRS range = 0 (worst) to 100 (best)

   Assessment of change in BCVA (ETDRS letter score) from baseline at all visits

3. Mean change from baseline in central subfield thickness (CST [μm]) to the average of Months 9 and 10 scores [ Time Frame: Baseline through 10 months ]
   Assessment of change in CST (μm) measurement from baseline compared to the average OCT CST (μm) measurements at Months 9 and 10
4. Mean change from baseline in CST (μm) at all visits [ Time Frame: Baseline through 12 months ]

   CST = central subfield thickness

   Assessment of change in CST (μm) measurement from baseline at all visits

5. Mean change from thickest observed CST (μm) prior to enrollment (pre-enrollment baseline) at all visits [ Time Frame: Screening through 12 months ]

   CST = central subfield thickness

   Assessment of change from thickest observed CST (μm) prior to enrollment (pre-enrollment baseline) compared to CST (μm) at all visits

6. Time to rescue treatment [ Time Frame: Baseline through 12 months ]
   Assessment of time to rescue treatment over 12 months of treatment
7. Mean number of intravitreal injections [ Time Frame: Baseline through 12 months ]
   Assessment of the mean number of intravitreal injections over 12 months of treatment
8. Proportion of subjects with absence of exudation (intra-/sub-retinal fluid/cystoid edema) at Months 9 and 12 of treatment [ Time Frame: Baseline through 12 months ]
   Assessment of the percentage of subjects with absence of exudation (intra-/sub-retinal fluid/cystoid edema) at Months 9 and 12 of treatment
9. Proportion of subjects who gained ≥ 15 ETDRS letters at Months 9 and 12 of treatment [ Time Frame: Baseline through 12 months ]

   ETDRS = early treatment of diabetic

   Assessment of the proportion of subjects who gained ≥ 15 ETDRS letters at Months 9 and 12 of treatment

10. Proportion of subjects who lost ≥ 15 ETDRS letters at Months 9 and 12 of treatment [ Time Frame: Baseline through 12 months ]

    ETDRS = early treatment of diabetic

    Assessment of the percentage of subjects who lost ≥ 15 ETDRS letters at Months 9 and 12 of treatment

11. Proportion of subjects with BCVA worse than 20/200 (Snellen equivalent) at Months 9 and 12 of treatment [ Time Frame: Baseline through 12 months ]

    Assessment of the percentage of subjects with BCVA worse than 20/200 (Snellen equivalent) at Months 9 and 12 of treatment

    A vision score of 20/20 is considered normal. A vision score of 20/200 is considered legally blind.

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females ≥ 50 years of age
• Presence of a CNV lesion secondary to AMD treated with at least 3 prior IVT injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab).
• Demonstrated response to prior anti-VEGF treatment since diagnosis
• BCVA of 35 letters or better

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 or IOP
• Chronic renal disease
• Abnormal liver function
• Women who are pregnant or lactating

Contacts and Locations

Contacts

Contact: VP, Global Clinical Development Operations; (650) 487-2800; vsmith@graybug.com

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Sponsors and Collaborators

Graybug Vision

Investigators

• Study Director: Chief Medical Officer; Graybug Vision, Inc.

More Information

• Responsible Party: Graybug Vision
• ClinicalTrials.gov Identifier: NCT03953079 History of Changes
• Other Study ID Numbers: GBV-102-002
• First Posted: May 16, 2019
• Last Update Posted: November 21, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Graybug Vision:

Age-related macular degeneration; Choroidal neovascularization

Additional relevant MeSH terms:

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Sunitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action