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
Primary Purpose
Wet Age-related Macular Degeneration, Retinal Vein Occlusion, Diabetic Macular Edema
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KSI-301
Sponsored by
About this trial
This is an interventional treatment trial for Wet Age-related Macular Degeneration focused on measuring DME, wAMD, RVO, KSI-301, Kodiak
Eligibility Criteria
Inclusion Criteria:
Wet AMD Cohort
- Treatment naïve wet age-related macular degeneration involving the fovea.
- A lesion area <30 mm2 (12 disc areas) of any lesion type.
- BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
- Decrease in vision in the study eye determined by the investigator to be primarily the result of wAMD.
DME Cohort
- Treatment naïve diabetic macular edema.
- BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
- Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
- Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.
RVO Cohort
- Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment.
- BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
- Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
- Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible.
- 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:
- Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye.
- Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye.
- Prior intravitreal anti-VEGF therapy in the study eye.
DME Cohort:
- Initial diagnosis of DME of more than 6 months from screening in the study eye.
- Hard exudates in the fovea.
- Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
- Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye.
- 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:
- Initial diagnosis of RVO of more than 4 months from screening in the study eye.
- Active retinal or iris neovascularization in the study eye.
- Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
For all phase 1b subjects:
- Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
- History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
- Any history of uveitis in either eye.
- 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.
- Prior vitrectomy surgery in the study eye.
- Active retinal disease other than the conditions under investigation.
- Active ocular or periocular infection or inflammation in either eye.
Sites / Locations
- Retinal Research Institute, LLC
- Retina Vitreous Associates Medical Group
- Northern California Retina Vitreous Associates
- Byers Eye Institute at Stanford
- Retina Vitreous Associates of Florida
- Sierra Eye Associates
- Mid Atlantic Retina
- Retina Research Institute of Texas
- Austin Clinical Research
- Retina Consultants of Texas
- Retina Consultants of Texas Woodlands
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
KSI-301 2.5 mg
KSI-301 5 mg
Arm Description
KSI-301 2.5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
KSI-301 5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
Outcomes
Primary Outcome Measures
Incidence of ocular (study eye) and systemic adverse events
Secondary Outcome Measures
Full Information
NCT ID
NCT03790852
First Posted
December 27, 2018
Last Updated
November 1, 2022
Sponsor
Kodiak Sciences Inc
1. Study Identification
Unique Protocol Identification Number
NCT03790852
Brief Title
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
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
All patients past planned primary endpoint; decision by Sponsor to wind down open-label follow-up activities.
Study Start Date
December 26, 2018 (Actual)
Primary Completion Date
June 2, 2021 (Actual)
Study Completion Date
June 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kodiak Sciences Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wet Age-related Macular Degeneration, Retinal Vein Occlusion, Diabetic Macular Edema
Keywords
DME, wAMD, RVO, KSI-301, Kodiak
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KSI-301 2.5 mg
Arm Type
Experimental
Arm Description
KSI-301 2.5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
Arm Title
KSI-301 5 mg
Arm Type
Experimental
Arm Description
KSI-301 5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
Intervention Type
Drug
Intervention Name(s)
KSI-301
Intervention Description
Intravitreal injection
Primary Outcome Measure Information:
Title
Incidence of ocular (study eye) and systemic adverse events
Time Frame
Week 72
Other Pre-specified Outcome Measures:
Title
Mean change in central retinal thickness on optical coherence tomography
Time Frame
Baseline, Week 72
Title
Mean change in best corrected visual acuity
Time Frame
Baseline, Week 72
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Wet AMD Cohort
Treatment naïve wet age-related macular degeneration involving the fovea.
A lesion area <30 mm2 (12 disc areas) of any lesion type.
BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
Decrease in vision in the study eye determined by the investigator to be primarily the result of wAMD.
DME Cohort
Treatment naïve diabetic macular edema.
BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.
RVO Cohort
Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment.
BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible.
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:
Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye.
Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye.
Prior intravitreal anti-VEGF therapy in the study eye.
DME Cohort:
Initial diagnosis of DME of more than 6 months from screening in the study eye.
Hard exudates in the fovea.
Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye.
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:
Initial diagnosis of RVO of more than 4 months from screening in the study eye.
Active retinal or iris neovascularization in the study eye.
Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
For all phase 1b subjects:
Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
Any history of uveitis in either eye.
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.
Prior vitrectomy surgery in the study eye.
Active retinal disease other than the conditions under investigation.
Active ocular or periocular infection or inflammation in either eye.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Ehrlich, MD, PhD
Organizational Affiliation
Kodiak Sciences Inc
Official's Role
Study Director
Facility Information:
Facility Name
Retinal Research Institute, LLC
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85053
Country
United States
Facility Name
Retina Vitreous Associates Medical Group
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Northern California Retina Vitreous Associates
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Byers Eye Institute at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Retina Vitreous Associates of Florida
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33711
Country
United States
Facility Name
Sierra Eye Associates
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Mid Atlantic Retina
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Retina Research Institute of Texas
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Austin Clinical Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78750
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 Woodlands
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77384
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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