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

Primary Purpose

Neovascular Age-related Macular Degeneration

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CLS-AX
Anti-VEGF
Sponsored by
Clearside Biomedical, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration focused on measuring AMD, Wet-AMD, suprachoroidal, tyrosine kinase inhibitor, Microinjector, SCS

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Retinal Consultants of Arizona
  • California Retina Consultants
  • Northern California Retina Vitreous Associates Medical Group, LLC
  • Retinal Consultants Medical Group
  • Center for Retina and Macular Disease
  • Southeast Retina Center
  • Cumberland Valley Retina Consultants
  • Austin Retina Associates
  • Retina Consultants of Texas
  • Retina Consultants of Texas
  • Retina Consultants of Texas

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1 (Low Dose)

Cohort 2 (Low-mid Dose)

Cohort 3 (High-mid Dose)

Cohort 4 (High Dose)

Arm Description

Subjects will receive a low dose of 0.03 mg CLS-AX

Subjects will receive a low-mid dose of 0.10 mg CLS-AX

Subjects will receive a high-mid dose of 0.50 mg CLS-AX

Subjects will receive a high-mid dose of 1.0 mg CLS-AX

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit.
Number of Participants With Serious Adverse Events
Number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit.

Secondary Outcome Measures

Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
Intraocular pressure (IOP) is a diagnostic measurement of the fluid pressure, measured in millimeters of mercury, inside the eye. IOP was measured using Goldmann applanation tonometry or by use of a Tonopen tonometer. Normal eye pressure is usually considered to be between 10 and 20 mmHg (AAO.org). Untreated elevated eye pressure is a risk factor for glaucoma.
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Number of participants receiving additional intravitreal aflibercept injections during the course of the study for nAMD. Participants qualified to receive additional IVT aflibercept injections based on protocol-defined criteria, including 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness >75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye. Additionally, a participant could receive additional IVT aflibercept injections in the study eye for reasons beyond the protocol-defined criteria if it was in the participant's best interest per the Investigator's judgment following best medical practice.
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Number of participants qualifying to receive additional intravitreal aflibercept injections during the course of the study. Criteria included 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness >75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye.
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A central reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. Only images that were gradable by the central reading center were included in the analysis.
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
BCVA measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting test distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Maximum Plasma Concentration [Cmax] of Axitinib
Maximum (or peak) plasma concentration of axitinib during the course of the study. Plasma samples were collected pre-dose at Baseline, 60 minutes post-dose at Baseline, and at Weeks 4 and 12. Peak quantifiable levels, based on a lower level of quantitation (LLOQ) of 0.01 ng/mL, were included in the analysis.

Full Information

First Posted
November 2, 2020
Last Updated
August 28, 2023
Sponsor
Clearside Biomedical, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04626128
Brief Title
Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD
Acronym
OASIS
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 15, 2020 (Actual)
Primary Completion Date
October 13, 2022 (Actual)
Study Completion Date
October 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clearside Biomedical, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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)
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-related Macular Degeneration
Keywords
AMD, Wet-AMD, suprachoroidal, tyrosine kinase inhibitor, Microinjector, SCS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
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)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (Low Dose)
Arm Type
Experimental
Arm Description
Subjects will receive a low dose of 0.03 mg CLS-AX
Arm Title
Cohort 2 (Low-mid Dose)
Arm Type
Experimental
Arm Description
Subjects will receive a low-mid dose of 0.10 mg CLS-AX
Arm Title
Cohort 3 (High-mid Dose)
Arm Type
Experimental
Arm Description
Subjects will receive a high-mid dose of 0.50 mg CLS-AX
Arm Title
Cohort 4 (High Dose)
Arm Type
Experimental
Arm Description
Subjects will receive a high-mid dose of 1.0 mg CLS-AX
Intervention Type
Drug
Intervention Name(s)
CLS-AX
Other Intervention Name(s)
axitinib injectable suspension
Intervention Description
injectable suspension of small molecule tyrosine kinase inhibitor (TKI)
Intervention Type
Drug
Intervention Name(s)
Anti-VEGF
Other Intervention Name(s)
aflibercept (2mg)
Intervention Description
Standard of care therapy used to block vascular endothelial growth factor
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
Number of participants with treatment-emergent adverse events (TEAEs) reported between the administration of CLS-AX and study exit.
Time Frame
Day 1 to Week 12
Title
Number of Participants With Serious Adverse Events
Description
Number of participants with serious adverse events (SAEs) reported between the administration of CLS-AX and study exit.
Time Frame
Day 1 to Week 12
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Pre Injection Intraocular Pressure (IOP)
Description
Intraocular pressure (IOP) is a diagnostic measurement of the fluid pressure, measured in millimeters of mercury, inside the eye. IOP was measured using Goldmann applanation tonometry or by use of a Tonopen tonometer. Normal eye pressure is usually considered to be between 10 and 20 mmHg (AAO.org). Untreated elevated eye pressure is a risk factor for glaucoma.
Time Frame
Weeks 4, 8 and 12.
Title
Number of Participants Receiving Additional Intravitreal (IVT) Aflibercept Injections
Description
Number of participants receiving additional intravitreal aflibercept injections during the course of the study for nAMD. Participants qualified to receive additional IVT aflibercept injections based on protocol-defined criteria, including 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness >75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye. Additionally, a participant could receive additional IVT aflibercept injections in the study eye for reasons beyond the protocol-defined criteria if it was in the participant's best interest per the Investigator's judgment following best medical practice.
Time Frame
From Day 1 to Week 12
Title
Number of Participants Qualifying to Receive Additional Intravitreal (IVT) Aflibercept Injections
Description
Number of participants qualifying to receive additional intravitreal aflibercept injections during the course of the study. Criteria included 1) loss of 10 or more letters in BCVA compared to the best prior study-assessed BCVA in the study eye that was attributed to intra- or sub-retinal fluid, 2) increase in central subfield thickness >75 microns from Baseline in the study eye, or 3) presence of vision-threatening hemorrhage due to AMD in the study eye.
Time Frame
Day 1 to Week 12
Title
Mean Change From Baseline (Visit 2) in Central Subfield Thickness (CST) in the Study Eye
Description
Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A central reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. Only images that were gradable by the central reading center were included in the analysis.
Time Frame
Weeks 4, 8 and 12
Title
Mean Change From Baseline (Visit 2) in Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Description
BCVA measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting test distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Time Frame
Weeks 4, 8 and 12
Title
Maximum Plasma Concentration [Cmax] of Axitinib
Description
Maximum (or peak) plasma concentration of axitinib during the course of the study. Plasma samples were collected pre-dose at Baseline, 60 minutes post-dose at Baseline, and at Weeks 4 and 12. Peak quantifiable levels, based on a lower level of quantitation (LLOQ) of 0.01 ng/mL, were included in the analysis.
Time Frame
Day 1 to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Coultas, PhD
Organizational Affiliation
Clearside Biomedical, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Retinal Consultants of Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85014
Country
United States
Facility Name
California Retina Consultants
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Northern California Retina Vitreous Associates Medical Group, LLC
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Retinal Consultants Medical Group
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Center for Retina and Macular Disease
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Southeast Retina Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
Cumberland Valley Retina Consultants
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Austin Retina Associates
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Retina Consultants of Texas
City
Bellaire
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
Facility Name
Retina Consultants of Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Retina Consultants of Texas
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77384
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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