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

• ClinicalTrials.gov Identifier: NCT03790852
• Recruitment Status: Active, not recruiting
• First Posted: January 2, 2019
• Last Update Posted: July 2, 2020
• Sponsor: Kodiak Sciences Inc
• Information provided by (Responsible Party): Kodiak Sciences Inc

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Wet Age-related Macular Degeneration; Retinal Vein Occlusion; Diabetic Macular Edema	Drug: KSI-301	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: December 26, 2018
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: January 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of ocular (study eye) and systemic adverse events [ Time Frame: Week 72 ]

Other Outcome Measures:

1. Mean change in central retinal thickness on optical coherence tomography [ Time Frame: Baseline, Week 72 ]
2. Mean change in best corrected visual acuity [ Time Frame: Baseline, Week 72 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Kodiak Sciences Investigative Site

Phoenix, Arizona, United States, 85053

United States, California

Kodiak Sciences Investigative Site

Beverly Hills, California, United States, 90211

Kodiak Sciences Investigative Site

Mountain View, California, United States, 94040

Kodiak Sciences Investigative Site

Palo Alto, California, United States, 94303

Kodiak Sciences Investigative Site

San Francisco, California, United States, 94109

United States, Florida

Kodiak Sciences Investigative Site

Saint Petersburg, Florida, United States, 33711

United States, Nevada

Kodiak Sciences Investigative Site

Reno, Nevada, United States, 89502

United States, Pennsylvania

Kodiak Sciences Investigative Site

Philadelphia, Pennsylvania, United States, 19107

United States, South Carolina

Kodiak Sciences Investigative Site

Florence, South Carolina, United States, 29501

United States, Texas

Kodiak Sciences Investigative Site

Abilene, Texas, United States, 79606

Kodiak Sciences Investigative Site

Austin, Texas, United States, 78705

Kodiak Sciences Investigative Site

Houston, Texas, United States, 77030

Kodiak Sciences Investigative Site

The Woodlands, Texas, United States, 77384

Sponsors and Collaborators

Kodiak Sciences Inc

More Information

• Responsible Party: Kodiak Sciences Inc
• ClinicalTrials.gov Identifier: NCT03790852
• Other Study ID Numbers: KSI-CL-101
• First Posted: January 2, 2019
• Last Update Posted: July 2, 2020
• Last Verified: June 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kodiak Sciences Inc:

DME; wAMD; RVO; KSI-301; Kodiak

Additional relevant MeSH terms:

Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases