Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO

A Phase 1/1b Open Label, Multi-center Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With Wet Age-Related Macular Degeneration (wAMD), Diabetic Macular Edema (DME) and Retinal Vein Occlusion (RVO)

This is a Phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at two dose levels: 2.5 mg and 5 mg

Study Overview

• Status: Terminated
• Conditions: Diabetic Macular Edema; Retinal Vein Occlusion; Wet Age-related Macular Degeneration
• Intervention / Treatment: Drug: KSI-301

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute, LLC
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford
  • Florida
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Associates of Florida
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Wet AMD Cohort

1. Treatment naïve wet age-related macular degeneration involving the fovea.
2. A lesion area <30 mm2 (12 disc areas) of any lesion type.
3. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
4. Decrease in vision in the study eye determined by the investigator to be primarily the result of wAMD.

DME Cohort

1. Treatment naïve diabetic macular edema.
2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
4. Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.

RVO Cohort

1. Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment.
2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
4. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible.
5. Decrease in vision in the study eye determined by the investigator to be primarily the result of macular edema secondary to RVO.

General Inclusion Criteria

• Adults ≥ 21 years.

Exclusion Criteria:

Wet AMD Cohort:

1. Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye.
2. Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye.
3. Prior intravitreal anti-VEGF therapy in the study eye.

DME Cohort:

1. Initial diagnosis of DME of more than 6 months from screening in the study eye.
2. Hard exudates in the fovea.
3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
4. Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye.
5. Fibrovascular proliferation or tractional retinal detachment in the posterior pole in the study eye. If traction is present outside the posterior pole, it should be considered not at risk of increasing and threatening the macula with the use of anti-VEGF injections, in the investigator's judgement.

RVO Cohort:

1. Initial diagnosis of RVO of more than 4 months from screening in the study eye.
2. Active retinal or iris neovascularization in the study eye.
3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.

For all phase 1b subjects:

1. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
2. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
3. Any history of uveitis in either eye.
4. Significant media opacities, including visually significant cataract, in the study eye that might interfere with visual acuity assessments, optical coherence tomography, fundus photography, or with examination of the eye for assessment of safety.
5. Prior vitrectomy surgery in the study eye.
6. Active retinal disease other than the conditions under investigation.
7. Active ocular or periocular infection or inflammation in either eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KSI-301 2.5 mg; KSI-301 2.5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria	Drug: KSI-301; Intravitreal injection
Experimental: KSI-301 5 mg; KSI-301 5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria	Drug: KSI-301; Intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of ocular (study eye) and systemic adverse events	Week 72

Other Outcome Measures

Outcome Measure	Time Frame
Mean change in central retinal thickness on optical coherence tomography	Baseline, Week 72
Mean change in best corrected visual acuity	Baseline, Week 72

Collaborators and Investigators

• Sponsor: Kodiak Sciences Inc
• Investigators: Study Director: Pablo Velazquez-Martin, MD, Kodiak Sciences Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2018
• Primary Completion (Actual): June 2, 2021
• Study Completion (Actual): June 9, 2022

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: December 31, 2018
• First Posted (Actual): January 2, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: RVO; DME; wAMD; KSI-301; Kodiak
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion
• Other Study ID Numbers: KSI-CL-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No