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A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD)

Phase 3
Completed
Conditions
Wet Age-related Macular Degeneration
Interventions
Other: Sham Procedure
Registration Number
NCT04964089
Lead Sponsor
Kodiak Sciences Inc
Brief Summary

This Phase 3 study will evaluate the efficacy and safety of KSI-301 compared to aflibercept, in participants with neovascular (wet) age-related macular degeneration (wAMD)

Detailed Description

This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with visual impairment due to treatment-naïve neovascular (wet) age-related macular degeneration (wAMD)

The primary endpoint will be assessed as an average of Weeks 40, 44, and 48; additional secondary endpoints for efficacy will be assessed by visit over time

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
557
Inclusion Criteria
  • Signed informed consent prior to participation in the study.
  • Treatment-naïve choroidal neovascularization (CNV) secondary to AMD.
  • BCVA ETDRS score between 83 and 25 letters, inclusive, in the Study Eye.
  • Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wAMD.
  • Other protocol-specified inclusion criteria may apply
Exclusion Criteria
  • BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular).
  • Active or suspected ocular or periocular infection or inflammation.
  • CNV secondary to other causes in the Study Eye.
  • Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or affect macular edema or alter visual acuity during the study.
  • Uncontrolled glaucoma in the Study Eye.
  • Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT or fundus photography.
  • Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening.
  • Women who are pregnant or lactating or intending to become pregnant during the study.
  • Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
  • History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
  • Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100 mmHg while at rest.
  • Other protocol-specified exclusion criteria may apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Aflibercept (Treatment Group B)Sham ProcedureIntravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered.
KSI-301 (Treatment Group A)KSI-301Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44.
Aflibercept (Treatment Group B)AfliberceptIntravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered.
Primary Outcome Measures
NameTimeMethod
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to the Average of Non-missing BCVA Values of Weeks 40, 44 and 48.Day 1 to Week 48

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.

Secondary Outcome Measures
NameTimeMethod
Proportion of Participants With BCVA Snellen Equivalent of 20/200 or Worse Over Time (≤38 ETDRS Letters)Day 1 to Week 48

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.

Proportion of Patients Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over TimeDay 1 to Week 48

Categorical improvements in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Mean Change in Best Corrected Visual Acuity (BCVA) by Visit Over TimeDay 1 to Week 48

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.

Proportion of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters)Day 1 to Week 48

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.

Proportion of Patients Who Lost ≥ 5, ≥10 and ≥15 Letters From Baseline Over TimeDay 1 to Week 48

Categorical worsening in Best Corrected Visual Acuity (BCVA) of clinically relevant BCVA measurements corresponding to 1, 2 and 3 lines of the ETDRS vision testing chart

Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline to the Average of Weeks 40, 44 and 48 and Over TimeDay 1 to Week 48

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) as assessed by a central reading center.

Trial Locations

Locations (66)

Ophthalmic Consultants of Boston

🇺🇸

Boston, Massachusetts, United States

Retina Consultants of Texas

🇺🇸

Houston, Texas, United States

Medical Center Ophthalmology Associates

🇺🇸

San Antonio, Texas, United States

Tennessee Retina PC

🇺🇸

Nashville, Tennessee, United States

Retina Northwest

🇺🇸

Portland, Oregon, United States

Retina Associates of Orange County

🇺🇸

Laguna Hills, California, United States

Northwest Arkansas Retina Associates

🇺🇸

Springdale, Arkansas, United States

Eye Medical Center of Fresno

🇺🇸

Fresno, California, United States

Retina Consultants of Southern California

🇺🇸

Redlands, California, United States

Colorado Retina Associates PC

🇺🇸

Lakewood, Colorado, United States

Retina Group of New England

🇺🇸

Waterford, Connecticut, United States

Florida Eye Microsurgical Institute

🇺🇸

Boynton Beach, Florida, United States

Retina Specialty Institute

🇺🇸

Pensacola, Florida, United States

National Ophthalmic Research Institute

🇺🇸

Fort Myers, Florida, United States

Retina Vitreous Associates of Florida

🇺🇸

Saint Petersburg, Florida, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Talley Eye

🇺🇸

Evansville, Indiana, United States

Springfield Clinic LLP

🇺🇸

Springfield, Illinois, United States

Retina Associates PA

🇺🇸

Lenexa, Kansas, United States

Retina Associates of Kentucky

🇺🇸

Lexington, Kentucky, United States

Wolfe Eye Clinic

🇺🇸

West Des Moines, Iowa, United States

Cumberland Valley Retina Consultants PC

🇺🇸

Hagerstown, Maryland, United States

Retina Group of Washington

🇺🇸

Chevy Chase, Maryland, United States

New England Retina Consultants

🇺🇸

Springfield, Massachusetts, United States

Vitreo Retinal Associates PC

🇺🇸

Worcester, Massachusetts, United States

Foundation for Vision Research

🇺🇸

Grand Rapids, Michigan, United States

Vitreoretinal Surgery PA

🇺🇸

Edina, Minnesota, United States

NJ Retina

🇺🇸

Teaneck, New Jersey, United States

Retina Associates of Western NY

🇺🇸

Rochester, New York, United States

Sierra Eye Associates

🇺🇸

Reno, Nevada, United States

Western Carolina Retinal Associate PA

🇺🇸

Asheville, North Carolina, United States

Retina Associates of Cleveland

🇺🇸

Cleveland, Ohio, United States

MidAtlantic Retina

🇺🇸

Philadelphia, Pennsylvania, United States

Cascade Medical Research Institute

🇺🇸

Springfield, Oregon, United States

Black Hills Regional Eye Institute

🇺🇸

Rapid City, South Dakota, United States

Retina Research Institute of Texas

🇺🇸

Abilene, Texas, United States

Retina Consultants of Texas-(Katy)

🇺🇸

Katy, Texas, United States

Texas Retina Associates

🇺🇸

Plano, Texas, United States

Strategic Clinical Research Group, LLC

🇺🇸

Willow Park, Texas, United States

Retina Consultants of Texas - (Woodlands)

🇺🇸

The Woodlands, Texas, United States

Emanuelli Research & Development Center LLC

🇵🇷

Arecibo, Puerto Rico

Spokane Eye

🇺🇸

Spokane, Washington, United States

Retina Health Center

🇺🇸

Fort Myers, Florida, United States

Florida Eye Associates

🇺🇸

Melbourne, Florida, United States

Associated Retinal Consultants PC

🇺🇸

Royal Oak, Michigan, United States

The Retina Center of New Jersey

🇺🇸

Bloomfield, New Jersey, United States

Retina Consultants of Orange County

🇺🇸

Fullerton, California, United States

Northern California Retina Vitreous Associates

🇺🇸

Mountain View, California, United States

Retina Consultants of San Diego

🇺🇸

Poway, California, United States

Austin Retina Associates (Round Rock)

🇺🇸

Round Rock, Texas, United States

Retina Consultants, LLC

🇺🇸

Salem, Oregon, United States

Rand Eye Institute

🇺🇸

Deerfield Beach, Florida, United States

California Retina Consultants

🇺🇸

Bakersfield, California, United States

UCSD Jacobs Retina Center

🇺🇸

La Jolla, California, United States

Orange County Retina Medical Group

🇺🇸

Santa Ana, California, United States

Southeast Retina Center

🇺🇸

Augusta, Georgia, United States

Retina-Vitreous Surgeons of Central NY

🇺🇸

Liverpool, New York, United States

Charleston Neuroscience Institute

🇺🇸

Ladson, South Carolina, United States

Cleveland Clinic Foundation, Cole Eye Institute

🇺🇸

Cleveland, Ohio, United States

Austin Retina Associates

🇺🇸

Austin, Texas, United States

Southeastern Retina Associates PC

🇺🇸

Knoxville, Tennessee, United States

Retinal Research Institute, LLC

🇺🇸

Phoenix, Arizona, United States

Palmetto Retina Center

🇺🇸

West Columbia, South Carolina, United States

Retina Research of Beaufort

🇺🇸

Beaufort, South Carolina, United States

Retinal Consultants Medical Group Inc

🇺🇸

Sacramento, California, United States

Retina Associates of Florida

🇺🇸

Tampa, Florida, United States

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