DAZZLE: 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.

Sponsor

Kodiak Sciences Inc (Industry)

Overall Status

Terminated

CT.gov ID

NCT04049266

Collaborator

(none)

558

Enrollment

Locations

Arms

30.9

Actual Duration (Months)

7.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Wet Macular Degeneration	Drug: KSI-301 Drug: Aflibercept Other: Sham Procedure	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

558 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

A masked evaluating investigator will be responsible for subject care except the injections and the safety assessment following the injections. An unmasked treating investigator will perform the injections and assess patient safety following the injections.

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Sep 30, 2019

Actual Primary Completion Date :

Nov 17, 2021

Actual Study Completion Date :

Apr 26, 2022

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Mean change in Best Corrected Visual Acuity (BCVA) from Day 1. [Year 1]
BCVA is measured using ETDRS visual acuity charts.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85014
2	Northwest Arkansas Retina Associates	Springdale	Arkansas	United States	72762
3	California Retina Consultants	Bakersfield	California	United States	93309
4	Retina Vitreous Associates	Beverly Hills	California	United States	90211
5	Eye Medical Center of Fresno	Fresno	California	United States	93720
6	Retina Consultants of Orange County	Fullerton	California	United States	92835
7	UCSD Jacobs Retina Center	La Jolla	California	United States	92037
8	Retina Associates of Orange County	Laguna Hills	California	United States	92653
9	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
10	Retina Consultants of San Diego	Poway	California	United States	92064
11	Retinal Consultants Medical Group Inc	Sacramento	California	United States	95819
12	Orange County Retina Medical Group	Santa Ana	California	United States	92705
13	California Retina Consultants	Santa Maria	California	United States	93454
14	Colorado Retina Associates PC	Lakewood	Colorado	United States	80228
15	Florida Eye Microsurgical Institute	Boynton Beach	Florida	United States	33426
16	Rand Eye Institute	Deerfield Beach	Florida	United States	33064
17	Retina Health Center	Fort Myers	Florida	United States	33907
18	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
19	Florida Eye Associates	Melbourne	Florida	United States	32901
20	Retina Specialty Institute	Pensacola	Florida	United States	32503
21	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33703
22	Retina Associates of Florida	Tampa	Florida	United States	33609
23	Southeast Retina Center	Augusta	Georgia	United States	30909
24	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
25	Retina Associates PA	Lenexa	Kansas	United States	66215
26	Vitreo Retinal Consultants and Surgeons	Wichita	Kansas	United States	67214
27	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
28	Cumberland Valley Retina Consultants PC	Hagerstown	Maryland	United States	21740
29	New England Retina Consultants	Springfield	Massachusetts	United States	01103
30	Vitreo Retinal Associates PC	Worcester	Massachusetts	United States	01603
31	Foundation for Vision Research	Grand Rapids	Michigan	United States	49525
32	Associated Retinal Consultants PC	Royal Oak	Michigan	United States	78073
33	Vitreoretinal Surgery PA	Edina	Minnesota	United States	55435
34	Springfield Clinic LLP	Springfield	Missouri	United States	62703
35	Sierra Eye Associates	Reno	Nevada	United States	89502
36	The Retina Center of New Jersey	Bloomfield	New Jersey	United States	07017
37	NJ Retina	Teaneck	New Jersey	United States	07605
38	Retina Associates of Cleveland	Beachwood	Ohio	United States	44122
39	Retina Associates of Cleveland	Cleveland	Ohio	United States	44130
40	Cleveland Clinic Foundation, Cole Eye Institute	Cleveland	Ohio	United States	44195
41	Retina and Vitreous Center of Southern Oregon PC	Ashland	Oregon	United States	97520
42	Cascade Medical Research Institute	Eugene	Oregon	United States	97401
43	Retina Northwest	Portland	Oregon	United States	97210
44	Wills Eye Hospital	Philadelphia	Pennsylvania	United States	19107
45	Palmetto Retina Center	Florence	South Carolina	United States	29501
46	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
47	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
48	Southeastern Retina Associates PC	Knoxville	Tennessee	United States	37909
49	Tennessee Retina PC	Nashville	Tennessee	United States	37203
50	Retina Research Institute of Texas	Abilene	Texas	United States	79606
51	Austin Clinical Research, LLC	Austin	Texas	United States	78705
52	Austin Retina Associates	Austin	Texas	United States	78705
53	Retina Consultants of Texas	Bellaire	Texas	United States	77401
54	Retina Consultants of Texas (Katy)	Katy	Texas	United States	77494
55	Texas Retina Associates	Plano	Texas	United States	75075
56	Austin Retina Associates (Round Rock)	Round Rock	Texas	United States	78681
57	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
58	Retina Consultants of Texas (Woodlands)	The Woodlands	Texas	United States	77384
59	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
60	Axon Clinical, s.r.o.	Praha		Czechia	150 00
61	Universitätsklinikum Bonn	Bonn		Germany	53127
62	Medizinische Hochschule Hannover	Hannover		Germany	30625
63	Uniklinik Köln	Köln		Germany	50937
64	Universitatsklinikum Leipzig	Leipzig		Germany	04103
65	Pauls Stradins Clinical University Hospital	Riga		Latvia	1002
66	Riga Eastern Clinical University Hospital Clinic Bikernieki	Riga		Latvia	1038
67	Oftalmika Sp. z o.o.	Bydgoszcz		Poland	85-631
68	Gabinet Okulistyczny prof. E. Wylegala	Katowice		Poland	40-760
69	Retina Okulistyka Sp. z o.o. Sp. km.	Warszawa		Poland	01-364
70	Univerzitna nemocnica Bratislava	Bratislava		Slovakia	821 01
71	Nemocnica Trebisov - SVET ZDRAVIA - PPDS	Trebišov		Slovakia	075 01
72	Fakultna nemocnica Trencin	Trenčín		Slovakia	911 01
73	Fakultna nemocnica s poliklinikou Zilina	Žilina		Slovakia	012 07
74	Institut de La Macula i La Retina	Barcelona		Spain	08022
75	Hospital dos de Maig	Barcelona		Spain	08025