Study of Intravitreal KSI-301 in Patients With Neovascular (Wet) Age-related Macular Degeneration

A Phase 2b/3, Prospective, Randomised, 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 (DAZZLE)

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-003428-35-LV

Enrollment

550

Registered

2019-09-10

Start date

2020-01-03

Completion date

Unknown

Last updated

2022-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neovascular (Wet) Age-related Macular Degeneration MedDRA version: 20.1 Level: LLT Classification code 10067791 Term: Wet macular degeneration System Organ Class: 10015919 - Eye disorders MedDRA version: 20.0 Level: SOC Classification code 10015919 Term: Eye disorders System Organ Class: 10015919 - Eye disorders MedDRA version: 20.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders

Interventions

Product Name: KSI-301 Drug Product Product Code: KSI-301 Pharmaceutical Form: Solution for injection INN or Proposed INN: OG1953 CAS Number: 2411896-53-0 Current Sponsor code: OG1953 Other descriptive

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD, including subfoveal, juxtafoveal and extrafoveal lesions or retinal angiomatous proliferation (RAP) lesions with a CNV component that affect the central subfield as evidenced by FA or OCT in the Study Eye at Screening. 2.The CNV area in the Study Eye must be at least 50% of total lesion size at Screening. 3.A lesion area =65 years) yes F.1.3.1 Number of subjects for this age range 495

Exclusion criteria

Exclusion criteria: 1.BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular). 2.Active or suspected ocular or periocular infection or inflammation in either eye at Day 1. 3.CNV secondary to other causes in the Study Eye, including pathologic myopia, angioid streaks, prior trauma, ocular histoplasmosis, or others. 4.Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid, such as central serous chorioretinopathy. 5.Fibrosis or atrophy of >50% of the lesion size and/or involving the foveal center of the Study Eye at Screening 6.Subretinal blood affecting the foveal center of the Study Eye and/or more than 50% of the lesion size at Screening. 7.Any approved or investigational treatment for neovascular AMD (other than oral vitamin supplements) in the Study Eye at any time. 8.Prior macular laser (e.g., thermal laser or photodynamic therapy laser) in the Study Eye.

Design outcomes

Primary

Measure	Time frame
Main Objective: To demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA) from Day 1 to Year 1. Year 1 is defined as the mean of the Week 48 and 52 measurements. ;Secondary Objective: •To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg from Day 1 to Week 96 by assessing visual and anatomical parameters. •To evaluate the proportion of subjects maintained on a Q12W, Q16W, or Q20W dosing regimen of KSI-301 over the duration of the first 52 weeks. •To evaluate the safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg. •To assess the systemic pharmacokinetics and immunogenicity of KSI-301.;Primary end point(s): The primary endpoint of this study will be the mean change in BCVA from Day 1 to Year 1, comparing subjects receiving KSI-301 to aflibercept at a non-inferiority margin of 4 letters. Year 1 is defined as the mean BCVA at Weeks 48 and 52. ;Timepoint(s) of evaluation of this end point: Weeks 48 and 52	—

Measure

Time frame

Main Objective: To demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA) from Day 1 to Year 1. Year 1 is defined as the mean of the Week 48 and 52 measurements. ;Secondary Objective: •To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg from Day 1 to Week 96 by assessing visual and anatomical parameters. •To evaluate the proportion of subjects maintained on a Q12W, Q16W, or Q20W dosing regimen of KSI-301 over the duration of the first 52 weeks. •To evaluate the safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg. •To assess the systemic pharmacokinetics and immunogenicity of KSI-301.;Primary end point(s): The primary endpoint of this study will be the mean change in BCVA from Day 1 to Year 1, comparing subjects receiving KSI-301 to aflibercept at a non-inferiority margin of 4 letters. Year 1 is defined as the mean BCVA at Weeks 48 and 52. ;Timepoint(s) of evaluation of this end point: Weeks 48 and 52

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Secondary

Measure	Time frame
Secondary end point(s): At Year 1: •Proportion of subjects on a Q12W, Q16W or Q20W dosing regimen of KSI-301 at Week 52 •Proportion of subjects who gain = 5, =10 and =15 letters from baseline over time •Proportion of subjects who lose = 5, =10 and =15 letters from baseline over time •Mean change from baseline in BCVA from baseline to Week 12, Week 16, and over time •Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time •Mean change in OCT CST from baseline to Week 12, Week 16, and over time •Mean change in OCT intraretinal fluid volume from baseline to Week 12, Week 16, and over time •Mean change in OCT subretinal fluid volume from baseline to Week 12, Week 16, and over time •Proportion of subjects without intraretinal fluid on OCT from baseline to Week 12, Week 16 and over time •Proportion of subjects without subretinal fluid on OCT from baseline to Week 12, Week 16 and over time •Proportion of subjects without pigment epithelial detachments on OCT from baseline over time •Mean change in CNV total lesion area on FA from baseline at Year 1 •Mean chance in area of leakage on FA from baseline at Year 1 •Number of study drug injections received in the KSI-301 and aflibercept groups through Year 1 •For the KSI-301 group, the predictability of being on Q12W, Q16W, or Q20W dosing at the end of Year 1 on the basis of the first set of Disease Activity Assessments (at Weeks 20 and 24). At Year 2: •Proportion of subjects who gain = 5, =10 and =15 letters from baseline over time •Proportion of subjects who lose = 5, =10 and =15 letters from baseline over time •Mean change from baseline in BCVA from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time •Mean change in OCT CST from b	—

Measure

Time frame

Secondary end point(s): At Year 1: •Proportion of subjects on a Q12W, Q16W or Q20W dosing regimen of KSI-301 at Week 52 •Proportion of subjects who gain = 5, =10 and =15 letters from baseline over time •Proportion of subjects who lose = 5, =10 and =15 letters from baseline over time •Mean change from baseline in BCVA from baseline to Week 12, Week 16, and over time •Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time •Mean change in OCT CST from baseline to Week 12, Week 16, and over time •Mean change in OCT intraretinal fluid volume from baseline to Week 12, Week 16, and over time •Mean change in OCT subretinal fluid volume from baseline to Week 12, Week 16, and over time •Proportion of subjects without intraretinal fluid on OCT from baseline to Week 12, Week 16 and over time •Proportion of subjects without subretinal fluid on OCT from baseline to Week 12, Week 16 and over time •Proportion of subjects without pigment epithelial detachments on OCT from baseline over time •Mean change in CNV total lesion area on FA from baseline at Year 1 •Mean chance in area of leakage on FA from baseline at Year 1 •Number of study drug injections received in the KSI-301 and aflibercept groups through Year 1 •For the KSI-301 group, the predictability of being on Q12W, Q16W, or Q20W dosing at the end of Year 1 on the basis of the first set of Disease Activity Assessments (at Weeks 20 and 24). At Year 2: •Proportion of subjects who gain = 5, =10 and =15 letters from baseline over time •Proportion of subjects who lose = 5, =10 and =15 letters from baseline over time •Mean change from baseline in BCVA from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time •Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time •Mean change in OCT CST from b

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Countries

Czech Republic, Germany, Italy, Latvia, Poland, Slovakia, Spain, United Kingdom, United States

Contacts

Public ContactKSI-CL-102 Trial Information

Kodiak Sciences Inc

KSI-CL-102@kodiak.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026