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. (DAZZLE)

A Phase 2b/3, Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center Study to Investigate the Efficacy and Safety of Repeated Intravitreal Administration of KSI-301 in Subjects With Neovascular (Wet) Age-related Macular Degeneration.

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).

Study Overview

• Status: Terminated
• Conditions: Wet Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept; Drug: KSI-301; Other: Sham Procedure

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. At Week 52 patients on the aflibercept treatment arm will be re-randomized 1:1 into KSI-301 5 mg and aflibercept 2 mg.

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia, 150 00
    • Axon Clinical, s.r.o.
• Germany
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Köln, Germany, 50937
    • Uniklinik Köln
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, 1038
    • Riga Eastern Clinical University Hospital Clinic Bikernieki
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Sp. z o.o.
  • Katowice, Poland, 40-760
    • Gabinet Okulistyczny prof. E. Wylegala
  • Warszawa, Poland, 01-364
    • Retina Okulistyka Sp. z o.o. Sp. km.
• Slovakia
  • Bratislava, Slovakia, 821 01
    • Univerzitna nemocnica Bratislava
  • Trebišov, Slovakia, 075 01
    • Nemocnica Trebisov - SVET ZDRAVIA - PPDS
  • Trenčín, Slovakia, 911 01
    • Fakultna nemocnica Trencin
  • Žilina, Slovakia, 012 07
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Barcelona, Spain, 08022
    • Institut de la Macula i la retina
  • Barcelona, Spain, 08025
    • Hospital Dos de Maig
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute, LLC
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Northwest Arkansas Retina Associates
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates
    • Fresno, California, United States, 93720
      • Eye Medical Center of Fresno
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • La Jolla, California, United States, 92037
      • UCSD Jacobs Retina Center
    • Laguna Hills, California, United States, 92653
      • Retina Associates of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Poway, California, United States, 92064
      • Retina Consultants of San Diego
    • Sacramento, California, United States, 95819
      • Retinal Consultants Medical Group Inc
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Maria, California, United States, 93454
      • California Retina Consultants
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina Associates PC
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Fort Myers, Florida, United States, 33907
      • Retina Health Center
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Saint Petersburg, Florida, United States, 33703
      • Retina Vitreous Associates of Florida
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates PA
    • Wichita, Kansas, United States, 67214
      • Vitreo Retinal Consultants and Surgeons
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants PC
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • New England Retina Consultants
    • Worcester, Massachusetts, United States, 01603
      • Vitreo Retinal Associates PC
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Foundation for Vision Research
    • Royal Oak, Michigan, United States, 78073
      • Associated Retinal Consultants PC
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Vitreoretinal Surgery PA
  • Missouri
    • Springfield, Missouri, United States, 62703
      • Springfield Clinic LLP
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07017
      • The Retina Center of New Jersey
    • Teaneck, New Jersey, United States, 07605
      • NJ Retina
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Retina Associates of Cleveland
    • Cleveland, Ohio, United States, 44130
      • Retina Associates of Cleveland
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation, Cole Eye Institute
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Retina and Vitreous Center of Southern Oregon PC
    • Eugene, Oregon, United States, 97401
      • Cascade Medical Research Institute
    • Portland, Oregon, United States, 97210
      • Retina Northwest
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Hospital
  • South Carolina
    • Florence, South Carolina, United States, 29501
      • Palmetto Retina Center
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Institute
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Southeastern Retina Associates PC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Clinical Research, LLC
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Katy, Texas, United States, 77494
      • Retina Consultants of Texas (Katy)
    • Plano, Texas, United States, 75075
      • Texas Retina Associates
    • Round Rock, Texas, United States, 78681
      • Austin Retina Associates (Round Rock)
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas (Woodlands)
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KSI-301 5 mg; Drug: 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.	Drug: KSI-301; Intravitreal Injection; Other: 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.
Active Comparator: Aflibercept 2 mg; Drug: 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.	Drug: Aflibercept; Intravitreal Injection; Other Names: Eylea; Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in Best Corrected Visual Acuity (BCVA) from Day 1.	BCVA is measured using ETDRS visual acuity charts.	Year 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects on a Q12W, Q16W or Q20W dosing regimen of KSI-301.	Year 1
Proportion of subjects who gain ≥ 5, ≥10 and ≥15 letters from Day 1.	Year 1
Proportion of subjects who lose ≥ 5, ≥10 and ≥15 letters from Day 1.	Year 1
Proportion of subjects with BCVA Snellen equivalent of 20/40 or better.	Year 1
Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse.	Year 1
Mean change in OCT central subfield retinal thickness (CST) from Day 1.	Year 1
Mean change in OCT intraretinal fluid volume from Day 1.	Year 1
Mean change in OCT subretinal fluid volume from Day 1.	Year 1
Proportion of subjects without intraretinal fluid on OCT.	Year 1
Proportion of subjects without subretinal fluid on OCT.	Year 1
Mean change in CNV total lesion area on FA from baseline.	Year 1
Mean chance in area of leakage on FA from baseline.	Year 1

Collaborators and Investigators

• Sponsor: Kodiak Sciences Inc
• Investigators: Study Director: Jason Ehrlich, MD, PhD, Kodiak Sciences Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): November 17, 2021
• Study Completion (Actual): April 26, 2022

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: VEGF; Eye Diseases; AMD; Vascular endothelial growth factor; Wet AMD; Aflibercept; Retinal Diseases; Macular Degeneration; Anti-VEGF; Retinal Degeneration; KSI-301; Kodiak; Antibody biopolymer conjugate; Vision Disorders; Vision, low; Wet Macular Degeneration; choroidal neovascularization secondary to age-related macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: KSI-CL-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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