OASIS: Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD

Sponsor

Clearside Biomedical, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04626128

Collaborator

(none)

Enrollment

Locations

Arms

21.5

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of suprachoroidally administered CLS-AX following intravitreal anti-VEGF therapy in subjects with neovascular age-related macular degeneration (AMD)

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration	Drug: CLS-AX Drug: Anti-VEGF	Phase 1/Phase 2

Detailed Description

Multi-center, open-label, dose-escalation, phase 1/2a, safety and tolerability study to evaluate four dose groups of suprachoroidally administered CLS-AX following intravitreal anti-VEGF therapy in up to a maximum of 25 subjects with neovascular age-related macular degeneration

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Four groups of approximately 5 participants are assigned to receive interventions in sequential dose escalation fashion based on prior milestones being reached.Four groups of approximately 5 participants are assigned to receive interventions in sequential dose escalation fashion based on prior milestones being reached.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

OASIS: Open-label, Dose-escalation, Phase 1/2a Study of the Safety and Tolerability of Suprachoroidally Administered CLS-AX Following Intravitreal Anti-VEGF Therapy in Subjects With Neovascular Age-related Macular Degeneration

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (Low Dose) Subjects will receive a low dose of 0.03 mg CLS-AX	Drug: CLS-AX injectable suspension of small molecule tyrosine kinase inhibitor (TKI) Other Names: axitinib injectable suspension Drug: Anti-VEGF Standard of care therapy used to block vascular endothelial growth factor Other Names: aflibercept (2mg)
Experimental: Cohort 2 (Low-mid Dose) Subjects will receive a low-mid dose of 0.10 mg CLS-AX	Drug: CLS-AX injectable suspension of small molecule tyrosine kinase inhibitor (TKI) Other Names: axitinib injectable suspension Drug: Anti-VEGF Standard of care therapy used to block vascular endothelial growth factor Other Names: aflibercept (2mg)
Experimental: Cohort 3 (High-mid Dose) Subjects will receive a high-mid dose of 0.50 mg CLS-AX	Drug: CLS-AX injectable suspension of small molecule tyrosine kinase inhibitor (TKI) Other Names: axitinib injectable suspension Drug: Anti-VEGF Standard of care therapy used to block vascular endothelial growth factor Other Names: aflibercept (2mg)
Experimental: Cohort 4 (High Dose) Subjects will receive a high-mid dose of 1.0 mg CLS-AX	Drug: CLS-AX injectable suspension of small molecule tyrosine kinase inhibitor (TKI) Other Names: axitinib injectable suspension Drug: Anti-VEGF Standard of care therapy used to block vascular endothelial growth factor Other Names: aflibercept (2mg)

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs) [Day 1 to Week 12]
The number subject experiencing adverse events will be based on the Safety Population and will be limited to TEAEs. A TEAE is any adverse event occurring on or after the date and time of the SC injection of CLS-AX administration at Baseline (Visit 2, Day 1) or worsening relative to the pre CLS-AX state.
Incidence of serious adverse events [Day 1 to Week 12]
The number of subjects experiencing serious adverse events (SAEs). Serious adverse events are defined as a serious event that emerges following treatment with CLS-AX (administered at Visit 2 (Baseline, Day 1)), having been absent pre-treatment or worsens relative to the pre-treatment state

Secondary Outcome Measures

Change from baseline in pre injection Intraocular Pressure (IOP) [Day 1 to Week 12]
Changes from Baseline (Visit 2) pre injection IOP values in the study eye
Incidence of subjects receiving additional intravitreal (IVT) aflibercept injections [Day 1 to Week 12]
Number of subjects receiving additional intravitreal aflibercept injections during the course of the study
Incidence of subjects qualifying to receive additional intravitreal (IVT) aflibercept injections [Day 1 to Week 12]
Number of subjects qualifying to receive additional intravitreal aflibercept injections during the course of the study
Change from Baseline (Visit 2) in central subfield retinal thickness (CST) in the study eye [Day 1 to Week 12]
Mean change from Baseline (Visit 2) values in CST during the course of the study
Change from Baseline (Visit 2) in best corrected visual acuity (BCVA) letter score in the study eye [Day 1 to Week 12]
Mean change from Baseline (Visit 2) values in BCVA during the course of the study.
Maximum plasma concentration [Cmax] of axitinib [Day 1 to Week 12]
Maximum (or peak) plasma concentration of axitinib during the course of the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of neovascular age-related macular degeneration in the study eye.
Active subfoveal choroidal neovascularization (CNV) secondary to AMD
Two or more prior anti-VEGF intravitreal injections
EDTRS BCVA score ≤ 75 and ≥ 20 letters

Exclusion Criteria:

Any active ocular disease, ocular disorders or conditions, prior ocular surgery or infection in the study eye other than nAMD
Other than IVT anti-VEGF treatments, no topical ocular or intraocular or periocular corticosteroid, or other treatments for CNV
IOP ≥ 25mmHg or cup-to-disc ratio >0.8
Uncontrolled systemic disease (high risk or evidence of arterial and venous thromboembolism, CVA or stroke, unstable cardiovascular disease, uncontrolled hyperthyroidism, poor glycemic control, gastrointestinal bleed and/or high risk of GI perforation or fistula formation) or any other condition or therapy that would make the participant unsuitable for the study
Currently enrolled in an investigational drug or device study or has used an investigational drug or device within 30 days or the Screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona	Phoenix	Arizona	United States	85014
2	California Retina Consultants	Bakersfield	California	United States	93309
3	Northern California Retina Vitreous Associates Medical Group, LLC	Mountain View	California	United States	94040
4	Retinal Consultants Medical Group	Sacramento	California	United States	95825
5	Center for Retina and Macular Disease	Winter Haven	Florida	United States	33880
6	Southeast Retina Center	Augusta	Georgia	United States	30909
7	Cumberland Valley Retina Consultants	Hagerstown	Maryland	United States	21740
8	Austin Retina Associates	Austin	Texas	United States	78705
9	Retina Consultants of Texas	Bellaire	Texas	United States	77401
10	Retina Consultants of Texas	San Antonio	Texas	United States	78240
11	Retina Consultants of Texas	The Woodlands	Texas	United States	77384