A Depot Formulation of Sunitinib Malate (GB-102) in Subjects With Diabetic Macular Edema and Retinal Vein Occlusion

• Sponsor: Graybug Vision (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04085341
• Collaborator: (none)
• Enrollment: 21
• Locations: 6
• Arms: 2
• Actual Duration (Months): 8.8
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Phase 2a multicenter, open-label, parallel-arm design study to evaluate the safety, tolerability and pharmacodynamics of a single intravitreal injection comparing 2 dose levels of GB-102 on subjects with Diabetic Macular Edema and Retinal Vein Occlusion

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema; Retina Vein Occlusion	Drug: GB-102	Phase 2

Detailed Description

Phase 2a multicenter, open-label, parallel-arm design study to evaluate the safety, tolerability and pharmacodynamics of a single intravitreal injection comparing 2 dose levels (1 mg and 2 mg) of GB-102 on subjects with Diabetic Macular Edema and Retinal Vein Occlusion who have received prior treatment with anti-vascular endothelial growth factor (VEGF)

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel-arm designParallel-arm design
• Masking: None (Open Label)
• Masking Description: Open-label study design
• Primary Purpose: Treatment
• Official Title: A Phase 2a Multicenter Study Evaluating the Safety, Tolerability, and Pharmacodynamics of Sunitinib Malate Depot Formulation (GB-102) in Subjects With Diabetic Macular Edema (DME) and Retinal Vein Occlusion (RVO)
• Actual Study Start Date: Sep 11, 2019
• Actual Primary Completion Date: Jun 5, 2020
• Actual Study Completion Date: Jun 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GB-102 Dose 1 (1 mg) Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline.	Drug: GB-102; Intravitreal injection of GB-102; Other Names: Sunitinib malate
Experimental: GB-102 Dose 2 (2 mg) Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline.	Drug: GB-102; Intravitreal injection of GB-102; Other Names: Sunitinib malate

Outcome Measures

Primary Outcome Measures

1. Occurrence of Adverse Events (AEs) Across All Study Visits [Baseline through Month 6]

   Number of subjects with an adverse event across all study visits

Secondary Outcome Measures

1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) (ETDRS) at All Study Visits [Baseline to Month 6]

   BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA = 0 (worst) to 100 (best) Assessment of change in BCVA (ETDRS letter score) from baseline at all visits

2. Mean Change From Baseline in Central Subfield Thickness (CST) (SD-OCT) at All Study Visits [Baseline to Month 6]

   CST = central subfield thickness SD-OCT = spectral domain-optical coherence tomography Assessment of change in CST (μm) measurement from baseline at all visits

3. Time to Rescue Treatment [Baseline through Month 6]

   Assessment of time to rescue treatment over 6 months of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females ≥ 21 years of age

• Known diagnosis of macular edema secondary to diabetic macular edema or retinal vein occlusion 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 31 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute	Phoenix	Arizona	United States	85053
2	Southern Retina	Savannah	Georgia	United States	31405
3	Eye Care Institute	Louisville	Kentucky	United States	40206
4	Boston Retina	Boston	Massachusetts	United States	02482
5	Sierra Eye Associates	Reno	Nevada	United States	89502
6	Texoma Retina Center	Denison	Texas	United States	75020

Sponsors and Collaborators

• Graybug Vision

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2019
• Statistical Analysis Plan - Sep 18, 2020

More Information

Publications

None provided.

• Responsible Party: Graybug Vision
• ClinicalTrials.gov Identifier: NCT04085341
• Other Study ID Numbers: GBV-102-003
• First Posted: Sep 11, 2019
• Last Update Posted: Nov 22, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Graybug Vision: Macular Edema
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Sunitinib

Study Results

Participant Flow

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
Period Title: Overall Study
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)	Total
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (13.83)	65.1 (10.5)	64.9 (11.88)
Sex: Female, Male (Count of Participants)
Female	3 30%	4 36.4%	7 33.3%
Male	7 70%	7 63.6%	14 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%	0 0%	2 9.5%
Not Hispanic or Latino	8 80%	11 100%	19 90.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 18.2%	2 9.5%
White	10 100%	9 81.8%	19 90.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	11 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Adverse Events (AEs) Across All Study Visits
Description	Number of subjects with an adverse event across all study visits
Time Frame	Baseline through Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
Measure Participants	10	11
Count of Participants [Participants]	7 70%	10 90.9%

2. Secondary Outcome

Title	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) (ETDRS) at All Study Visits
Description	BCVA = best corrected visual acuity; ETDRS = early treatment of diabetic retinopathy BCVA = 0 (worst) to 100 (best) Assessment of change in BCVA (ETDRS letter score) from baseline at all visits
Time Frame	Baseline to Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
Measure Participants	10	11
Mean (Full Range) [letters]	-10.4	-16.7

3. Secondary Outcome

Title	Mean Change From Baseline in Central Subfield Thickness (CST) (SD-OCT) at All Study Visits
Description	CST = central subfield thickness SD-OCT = spectral domain-optical coherence tomography Assessment of change in CST (μm) measurement from baseline at all visits
Time Frame	Baseline to Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
Measure Participants	10	10
Mean (Full Range) [micrometers]	131.0	-37.4

4. Secondary Outcome

Title	Time to Rescue Treatment
Description	Assessment of time to rescue treatment over 6 months of treatment
Time Frame	Baseline through Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GB-102 Dose 1 (1 mg)	GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102	Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
Measure Participants	10	11
Median (95% Confidence Interval) [days]	90	120

Adverse Events

Time Frame	Adverse events (AEs) were collected from baseline for the duration of a subject's participation in the study (up to 180 days). AEs are reported as treatment-emergent.
Adverse Event Reporting Description	An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. Ocular AEs are presented for both study eye and non-study eye combined.
Arm/Group Title	GB-102 Dose 1 (1 mg)		GB-102 Dose 2 (2 mg)
Arm/Group Description	Participants will receive intravitreal (IVT) GB-102 (1 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102		Participants will receive intravitreal (IVT) GB-102 (2 mg) in the study eye at Baseline. GB-102: Intravitreal injection of GB-102
All Cause Mortality
	GB-102 Dose 1 (1 mg)		GB-102 Dose 2 (2 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Serious Adverse Events
	GB-102 Dose 1 (1 mg)		GB-102 Dose 2 (2 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		2/11 (18.2%)
Cardiac disorders
Acute Myocardial Infarction	1/10 (10%)	1	0/11 (0%)	0
Eye disorders
Corneal Oedema	0/10 (0%)	0	1/11 (9.1%)	1
Visual Impairment	0/10 (0%)	0	1/11 (9.1%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/10 (0%)	0	1/11 (9.1%)	2
Other (Not Including Serious) Adverse Events
	GB-102 Dose 1 (1 mg)		GB-102 Dose 2 (2 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		10/11 (90.9%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)	0	1/11 (9.1%)	1
Eye disorders
Blepharitis	1/10 (10%)	2	0/11 (0%)	0
Cataract	0/10 (0%)	0	1/11 (9.1%)	2
Posterior Capsule Opacification	0/10 (0%)	0	1/11 (9.1%)	2
Retinal Aneurysm	0/10 (0%)	0	1/11 (9.1%)	1
Eye Pain	2/10 (20%)	2	3/11 (27.3%)	3
Visual Acuity Reduced	2/10 (20%)	2	3/11 (27.3%)	3
Vitreous Floaters	2/10 (20%)	2	3/11 (27.3%)	3
Macular Edema	4/10 (40%)	4	0/11 (0%)	0
Vision Blurred	2/10 (20%)	2	1/11 (9.1%)	1
Visual Impairment	1/10 (10%)	1	1/11 (9.1%)	2
Iridocyclitis	0/10 (0%)	0	2/11 (18.2%)	2
Swelling of Eyelid	1/10 (10%)	1	1/11 (9.1%)	1
Cataract Nuclear	0/10 (0%)	0	1/11 (9.1%)	1
Conjunctival Irritation	0/10 (0%)	0	1/11 (9.1%)	1
Corneal Edema	0/10 (0%)	0	1/11 (9.1%)	1
Eye Irritation	0/10 (0%)	0	1/11 (9.1%)	1
Eye Edema	0/10 (0%)	0	1/11 (9.1%)	1
Iritis	0/10 (0%)	0	1/11 (9.1%)	1
Lacrimation Increased	0/10 (0%)	0	1/11 (9.1%)	1
Ocular Hyperaemia	1/10 (10%)	2	0/11 (0%)	0
Pterygium	1/10 (10%)	1	0/11 (0%)	0
Punctate Keratitis	1/10 (10%)	1	0/11 (0%)	0
Pupils Unequal	0/10 (0%)	0	1/11 (9.1%)	1
Gastrointestinal disorders
Diverticulum	0/10 (0%)	0	1/11 (9.1%)	1
Gastrointestinal Vascular Malformation Haemorrhagic	0/10 (0%)	0	1/11 (9.1%)	1
Infections and infestations
Chorioretinitis	0/10 (0%)	0	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Procedural Pain	0/10 (0%)	0	1/11 (9.1%)	1
Investigations
Blood Potassium Decreased	0/10 (0%)	0	1/11 (9.1%)	1
Product Residue Present	2/10 (20%)	2	6/11 (54.5%)	8
Intraocular Pressure Increased	0/10 (0%)	0	2/11 (18.2%)	4
Vital Dye Staining Cornea Present	0/10 (0%)	0	1/11 (9.1%)	1
Metabolism and nutrition disorders
Hyperkalaemia	0/10 (0%)	0	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	0/10 (0%)	0	1/11 (9.1%)	1
Renal and urinary disorders
Nephropathy	0/10 (0%)	0	1/11 (9.1%)	1
Vascular disorders
Peripheral Arterial Occlusive Disease	0/10 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

Too few subject numbers divided across multiple indications. The trial was conducted in 21 subjects with Diabetic Macular Edema, Branch Retinal Vein Occlusion and Central Retinal Vein Occlusion divided between two doses. Subjects had variable disease control and duration prior to entry.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any investigator wishing to publish or present any study finding must present a manuscript or abstract to Graybug Vision 120 days prior to submission for publication or presentation to provide Graybug Vision an opportunity for review and comment.