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

Keywords

• AMD
• Wet-AMD
• suprachoroidal
• tyrosine kinase inhibitor
• Microinjector
• SCS

Lead sponsor

Clearside Biomedical, Inc. is the lead sponsor of 14 studies on the registry; none are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.

Study arms

• Experimental
  Cohort 1 (Low Dose)

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

  Drug: CLS-AX · Drug: Anti-VEGF

• Experimental
  Cohort 2 (Low-mid Dose)

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

  Drug: CLS-AX · Drug: Anti-VEGF

• Experimental
  Cohort 3 (High-mid Dose)

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

  Drug: CLS-AX · Drug: Anti-VEGF

• Experimental
  Cohort 4 (High Dose)

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

  Drug: CLS-AX · Drug: Anti-VEGF

Interventions

• DrugCLS-AX

  injectable suspension of small molecule tyrosine kinase inhibitor (TKI)

  Also known as: axitinib injectable suspension

• DrugAnti-VEGF

  Standard of care therapy used to block vascular endothelial growth factor

  Also known as: aflibercept (2mg)

Primary outcomes

1. 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.

   Time frame: Day 1 to Week 12

2. 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.

   Time frame: Day 1 to Week 12

Secondary outcomes

1. 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.

   Time frame: Weeks 4, 8 and 12.

2. 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.

   Time frame: From Day 1 to Week 12

3. 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.

   Time frame: Day 1 to Week 12

4. 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.

   Time frame: Weeks 4, 8 and 12

5. 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.

   Time frame: Weeks 4, 8 and 12

6. 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.

   Time frame: Day 1 to Week 12

Baseline characteristics

2 further baseline measures are reported on the registry.

Study documents

• Protocol and statistical analysis plan · Apr 15, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No