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A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration.

Phase 2
Terminated
Conditions
Wet Macular Degeneration
Interventions
Other: Sham Procedure
Registration Number
NCT04049266
Lead Sponsor
Kodiak Sciences Inc
Brief Summary

This study will evaluate the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

Detailed Description

This study is divided into a 3-week screening period, a 92-week treatment period, and a final 4-week follow-up period. At baseline patients will be randomized 1:1 into two treatment arms: KSI-301 5 mg and aflibercept 2 mg.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
559
Inclusion Criteria
  • Signed informed consent prior to participation in the study.
  • Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD.
  • BCVA ETDRS score between 80 and 25 letters (Snellen equivalent of 20/25 to 20/320), inclusive.
  • Other protocol-specified inclusion criteria may apply
Exclusion Criteria
  • CNV secondary to other causes in the Study Eye.
  • Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid.
  • Any history or evidence of a concurrent intraocular condition in the Study Eye that, in the judgment of the Investigator, could require either medical or surgical intervention during the study to prevent or treat visual loss.
  • Active ocular or periocular infection or inflammation.
  • Prior administration of any approved or investigational treatment for neovascular AMD in the Study Eye.
  • Uncontrolled glaucoma in the Study Eye.
  • Women who are pregnant or lactating or intending to become pregnant during the study.
  • Stroke or myocardial infarction in the 6-month period prior to Day 1.
  • Uncontrolled blood pressure defined as a systolic value > 180 mmHg or diastolic value ≥100 mmHg while at rest.
  • 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.
  • Other protocol-specified exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
KSI-301 5 mgSham ProcedureDrug: KSI-301 5 mg. KSI-301 5 mg will be administered by intravitreal injection into the study eye at 12, 16, and 20 weeks intervals as specified in the study protocol. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Aflibercept 2 mgAfliberceptDrug: Aflibercept 2 mg. Aflibercept 2 mg will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Aflibercept 2 mgSham ProcedureDrug: Aflibercept 2 mg. Aflibercept 2 mg will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
KSI-301 5 mgKSI-301Drug: KSI-301 5 mg. KSI-301 5 mg will be administered by intravitreal injection into the study eye at 12, 16, and 20 weeks intervals as specified in the study protocol. Drug: Sham Procedure. The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48 and 52, Full Analysis Set Year 1Year 1

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
Percentage of Subjects on KSI-301 Arm With a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment IntervalYear 1

Percentage of subjects on KSI-301 arm achieving a Once Every 12-Weeks, 16-Weeks or 20-Weeks Treatment Interval based on individualized treatment response

Percentage of Subjects Gaining ≥ 5, ≥10 and ≥15 Letters in BCVA From Baseline in the Study Eye, Full Analysis Set Year 1Year 1

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

Percentage of Subjects Who Achieving BCVA Snellen Equivalent of 20/40 or Better in the Study Eye at Year 1Year 1

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. BCVA Snellen equivalent of 20/40 was defined as ≥69 ETDRS letters

Percentage of Subjects With BCVA Snellen Equivalent of 20/200 or Worse in the Study Eye at Year 1Year 1

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. BCVA Snellen equivalent of 20/200 or Worse was defined as BCVA ≤ 38 ETDRS Letters.

Mean Change in OCT Central Subfield Retinal Thickness (CST) From Day 1Year 1

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 (73)

Cleveland Clinic Foundation, Cole Eye Institute

🇺🇸

Cleveland, Ohio, United States

Medical Center Ophthalmology Associates

🇺🇸

San Antonio, Texas, United States

Vitreoretinal Surgery PA

🇺🇸

Edina, Minnesota, United States

Retinal Research Institute, LLC

🇺🇸

Phoenix, Arizona, United States

Retina Consultants of Orange County

🇺🇸

Fullerton, California, United States

Retina Vitreous Associates

🇺🇸

Beverly Hills, California, United States

Northwest Arkansas Retina Associates

🇺🇸

Springdale, Arkansas, United States

Eye Medical Center of Fresno

🇺🇸

Fresno, California, United States

UCSD Jacobs Retina Center

🇺🇸

La Jolla, California, United States

Northern California Retina Vitreous Associates

🇺🇸

Mountain View, California, United States

Retina Consultants of San Diego

🇺🇸

Poway, California, United States

Retinal Consultants Medical Group Inc

🇺🇸

Sacramento, California, United States

Rand Eye Institute

🇺🇸

Deerfield Beach, Florida, United States

Orange County Retina Medical Group

🇺🇸

Santa Ana, California, United States

Colorado Retina Associates PC

🇺🇸

Lakewood, Colorado, United States

Florida Eye Microsurgical Institute

🇺🇸

Boynton Beach, Florida, United States

Retina Health Center

🇺🇸

Fort Myers, Florida, United States

National Ophthalmic Research Institute

🇺🇸

Fort Myers, Florida, United States

Retina Specialty Institute

🇺🇸

Pensacola, Florida, United States

Retina Vitreous Associates of Florida

🇺🇸

Saint Petersburg, Florida, United States

Southeast Retina Center

🇺🇸

Augusta, Georgia, United States

Retina Associates PA

🇺🇸

Lenexa, Kansas, United States

Retina Associates of Kentucky

🇺🇸

Lexington, Kentucky, United States

Cumberland Valley Retina Consultants PC

🇺🇸

Hagerstown, Maryland, United States

New England Retina Consultants

🇺🇸

Springfield, Massachusetts, United States

Vitreo Retinal Associates PC

🇺🇸

Worcester, Massachusetts, United States

Associated Retinal Consultants PC

🇺🇸

Royal Oak, Michigan, United States

Springfield Clinic LLP

🇺🇸

Springfield, Missouri, United States

The Retina Center of New Jersey

🇺🇸

Bloomfield, New Jersey, United States

Sierra Eye Associates

🇺🇸

Reno, Nevada, United States

NJ Retina

🇺🇸

Teaneck, New Jersey, United States

Retina Associates of Cleveland

🇺🇸

Cleveland, Ohio, United States

Retina and Vitreous Center of Southern Oregon PC

🇺🇸

Ashland, Oregon, United States

Retina Northwest

🇺🇸

Portland, Oregon, United States

Wills Eye Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Cascade Medical Research Institute

🇺🇸

Eugene, Oregon, United States

Palmetto Retina Center

🇺🇸

Florence, South Carolina, United States

Retina Research Institute of Texas

🇺🇸

Abilene, Texas, United States

Tennessee Retina PC

🇺🇸

Nashville, Tennessee, United States

Charleston Neuroscience Institute

🇺🇸

Ladson, South Carolina, United States

Retina Consultants of Texas

🇺🇸

Bellaire, Texas, United States

Austin Retina Associates

🇺🇸

Austin, Texas, United States

Retina Consultants of Texas (Katy)

🇺🇸

Katy, Texas, United States

Texas Retina Associates

🇺🇸

Plano, Texas, United States

Austin Retina Associates (Round Rock)

🇺🇸

Round Rock, Texas, United States

Strategic Clinical Research Group, LLC

🇺🇸

Willow Park, Texas, United States

Axon Clinical, s.r.o.

🇨🇿

Praha, Czechia

Universitätsklinikum Bonn

🇩🇪

Bonn, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Uniklinik Köln

🇩🇪

Köln, Germany

Pauls Stradins Clinical University Hospital

🇱🇻

Riga, Latvia

Universitatsklinikum Leipzig

🇩🇪

Leipzig, Germany

Oftalmika Sp. z o.o.

🇵🇱

Bydgoszcz, Poland

Riga Eastern Clinical University Hospital Clinic Bikernieki

🇱🇻

Riga, Latvia

Gabinet Okulistyczny prof. E. Wylegala

🇵🇱

Katowice, Poland

Univerzitna nemocnica Bratislava

🇸🇰

Bratislava, Slovakia

Retina Okulistyka Sp. z o.o. Sp. km.

🇵🇱

Warszawa, Poland

Institut de La Macula i La Retina

🇪🇸

Barcelona, Spain

Hospital dos de Maig

🇪🇸

Barcelona, Spain

Retina Associates of Florida

🇺🇸

Tampa, Florida, United States

Austin Clinical Research, LLC

🇺🇸

Austin, Texas, United States

California Retina Consultants

🇺🇸

Santa Maria, California, United States

Retina Associates of Orange County

🇺🇸

Laguna Hills, California, United States

Florida Eye Associates

🇺🇸

Melbourne, Florida, United States

Wolfe Eye Clinic

🇺🇸

West Des Moines, Iowa, United States

Vitreo Retinal Consultants and Surgeons

🇺🇸

Wichita, Kansas, United States

Retina Consultants of Texas (Woodlands)

🇺🇸

The Woodlands, Texas, United States

Foundation for Vision Research

🇺🇸

Grand Rapids, Michigan, United States

Southeastern Retina Associates PC

🇺🇸

Knoxville, Tennessee, United States

Black Hills Regional Eye Institute

🇺🇸

Rapid City, South Dakota, United States

Nemocnica Trebisov - SVET ZDRAVIA - PPDS

🇸🇰

Trebišov, Slovakia

Fakultna nemocnica s poliklinikou Zilina

🇸🇰

Žilina, Slovakia

Fakultna nemocnica Trencin

🇸🇰

Trenčín, Slovakia

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