Clinical Trials Register

Summary
EudraCT Number:	2018-003428-35
Sponsor's Protocol Code Number:	KSI-CL-102
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-10-10
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2018-003428-35

A.3

Full title of the trial

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)

Prospektívne, randomizované, dvojito maskované, multicentrické klinické skúšanie fázy 2b/3 kontrolované aktívnym komparátorom, za účelom zistiť účinnosť a bezpečnosť skúšaného produktu KSI-301 po opakovanom intravitreálnom podaní u pacientov s neovaskulárnou (vlhkou) vekom podmienenou degeneráciou makuly (DAZZLE)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Klinické skúšanie intravitreálneho podania KSI-301 u pacientov s neovaskulárnou (vlhkou) vekom podmienenou degeneráciou makuly

A.4.1

Sponsor's protocol code number

KSI-CL-102

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04049266

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Kodiak Sciences Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Kodiak Sciences Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Kodiak Sciences Inc
B.5.2	Functional name of contact point	KSI-CL-102 Trial Information
B.5.3	Address:
B.5.3.1	Street Address	1200 Page Mill Road
B.5.3.2	Town/ city	Palo, Alto, California
B.5.3.3	Post code	94304
B.5.3.4	Country	United States
B.5.6	E-mail	KSI-CL-102@kodiak.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	KSI-301 Drug Product
D.3.2	Product code	KSI-301
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OG1953
D.3.9.1	CAS number	2411896-53-0
D.3.9.2	Current sponsor code	OG1953
D.3.9.3	Other descriptive name	OG1953 Drug Substance
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Eylea
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AFLIBERCEPT
D.3.9.1	CAS number	862111-32-8
D.3.9.4	EV Substance Code	SUB26987
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Neovascular (Wet) Age-related Macular Degeneration

E.1.1.1

Medical condition in easily understood language

Neovascular (Wet) Age-related Macular Degeneration

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10067791
E.1.2	Term	Wet macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10015919
E.1.2	Term	Eye disorders
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10071129
E.1.2	Term	Neovascular age-related macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

•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.

E.2.3

Trial contains a sub-study

E.3

Principal 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 <30 mm2 (12 disc areas) of any CNV lesion subtype in the Study Eye.
4.Intra and/or subretinal fluid and/or SHRM (subretinal hyperreflective material) affecting the central subfield of the Study Eye on OCT at Screening.
5.BCVA ETDRS score between 80 and 25 letters (20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye at Screening and reconfirmed at Day 1.
6.Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wAMD.
7.Capable of understanding the informed consent, provides signed and dated informed consent, and agrees to comply with protocol requirements.

E.4

Principal 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.

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Weeks 48 and 52

E.5.2

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 baseline 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 over time
•Proportion of subjects without subretinal fluid on OCT from baseline 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 2
•Mean chance in area of leakage on FA from baseline at Year 2

For BCVA and OCT, Year 1 is defined as the average measurement at Weeks 48 and 52 and Year 2 is defined as the average measurement at Weeks 92 and 96.

A full list of secondary endpoints, including the delineation of key versus additional secondary endpoints, will be outlined in the SAP.

E.5.2.1

Timepoint(s) of evaluation of this end point

Year 1 and Year 2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study according to the protocol is defined as the last follow-up visit of the last subject enrolled or a Sponsor decision to terminate the study, whichever comes first.
Study data may be collected beyond the end of the study.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

495

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

550

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After subjects complete their final follow-up visit or discontinue from the study prematurely, all subjects will return to standard of care treatment at the discretion of their treating physician. The Sponsor will not provide continued access to study treatment following the end of the study or the end of each subject’s study treatment period.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-01-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-04-26

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