Clinical Trials Register

Summary
EudraCT Number:	2021-000225-27
Sponsor's Protocol Code Number:	KS301P107
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-07-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Latvia - SAM

A.2

EudraCT number

2021-000225-27

A.3

Full title of the trial

A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared with Intravitreal Aflibercept in Participants with Neovascular (Wet) Age-related Macular Degeneration (wAMD)

A.3.1

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

A Study to Evaluate the Efficacy and Safety of KSI-301 Compared to Aflibercept in Participants with Neovascular (Wet) Age-related Macular Degeneration (wAMD)

A.3.2

Name or abbreviated title of the trial where available

Daylight

A.4.1

Sponsor's protocol code number

KS301P107

A.5.4

Other Identifiers

Name:

IND Number

Number:

136167

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-105 Trial Information
B.5.3	Address:
B.5.3.1	Street Address	2631 Hanover Street
B.5.3.2	Town/ city	Palo Alto
B.5.3.3	Post code	CA 94304
B.5.3.4	Country	United States
B.5.6	E-mail	ksi301clinical@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	iridescimab vidros
D.3.9.1	CAS number	2411896-53-0
D.3.9.2	Current sponsor code	OG1953
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.3.9.3	Other descriptive name	AFLIBERCEPT
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 (wAMD)

E.1.1.1

Medical condition in easily understood language

Neovascular (Wet) Age-related Macular Degeneration (wAMD)

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	20.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10064930
E.1.2	Term	Age-related 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	LLT
E.1.2	Classification code	10075568
E.1.2	Term	Wet 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 the change in best
corrected visual acuity (BCVA) from Day 1 to Week 40.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg over the study duration by assessing visual parameters.

To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg over the study duration by assessing anatomical parameters.

To evaluate the safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg.

To assess the systemic pharmacokinetics (exposure) and immunogenicity of KSI-301.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

5.1.1 Ocular Inclusion Criteria

1. Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD, including
subfoveal, juxtafoveal, and extrafoveal lesions, or retinal angiomatous proliferations (RAP)
lesions with a CNV component that affects 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. The lesion area in the Study Eye must be <30 mm2 (12-disc areas) and can include any CNV
lesion subtype.
4. Intra- and/or subretinal fluid and/or subretinal hyperreflective material (SHRM) affecting the
central subfield of the Study Eye on OCT at Screening.
5. BCVA ETDRS score between 83 and 25 letters, 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.

In cases where both eyes are eligible, the eye with the worse BCVA at the Screening Visit will
be selected as the Study Eye. If both eyes are eligible and have the same BCVA, the decision of
which eye to select as the Study Eye will be made by the Investigator. Only one eye per participant can participate in the study.

5.1.2 General Inclusion Criteria
7. Capable of giving signed informed consent as described in Appendix 1, which includes
compliance with the protocols and restrictions listed in the informed consent form (ICF) and
in this protocol.
8. Male or female ≥50 years of age.
9. For women of childbearing potential: agreement to remain as abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per
year during the treatment period and for at least 90 days after the last dose of study drug.
Women of childbearing potential must have a negative urine pregnancy test result within 28
days prior to Day 1. If the urine pregnancy test is positive, it must be confirmed with a serum
pregnancy test.
A woman is considered of childbearing potential if she is postmenarcheal, has not
reached a postmenopausal state (≥12 months of amenorrhea with no identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus). The definition of childbearing potential may be adapted for
alignment with local guidelines or requirements.
b. Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization, established, proper use of hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and
copper intrauterine devices.
c. Contraception methods that do not result in a failure rate of <1% per year such as cap,
diaphragm, or sponge with spermicide, or male or female condom with or without
spermicide, are not acceptable.
d. The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the participant. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.

10. For men: agreement to remain abstinent or use contraceptive measures and agreement to
refrain from donating sperm, as defined below:
a. With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of <1% per year during the treatment period and for at least 30 days plus 90 days (a
spermatogenesis cycle) after the last dose of study drug. Men must refrain from
donating sperm during this same time period.
11. Ability and willingness to undertake all the scheduled visits and assessments.

E.4

Principal exclusion criteria

5.2.1 Ocular Exclusion Criteria
Where applicable exclusion criteria will be confirmed or assessed by the independent, masked
image Reading Center.
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 Screening
or on 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. Retinal pigment epithelium tear or rip in the Study Eye at Screening or on Day 1.
8. Any approved or investigational treatment for neovascular AMD (other than oral vitamin
supplements) in the Study Eye at any time.
9. Prior macular laser (e.g., thermal laser or photodynamic therapy laser) in the Study Eye.
10. Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the
opinion of the Investigator could require either medical or surgical intervention or affect
macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal
membrane).
11. History of cataract surgery and/or minimally invasive glaucoma surgery (MIGS) in the Study
Eye within 2 months of screening.
12. History of Yttrium-Aluminum Garnet (YAG) laser capsulotomy in the Study Eye within 2
months of screening.
13. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with
antiglaucoma medication) in the Study Eye.
14. History of glaucoma-filtering surgery (trabeculectomy or tube shunt) in the Study Eye.
15. History of retinal detachment or treatment or surgery for retinal detachment in the Study Eye.
16. History of uveitis in either eye.
17. Significant media opacities, including cataract, in the Study Eye that might interfere with
visual acuity, assessment of safety, OCT or fundus photography.
18. Cataract in the Study Eye that in the judgment of the Investigator is expected to require
surgical extraction within 12 months of screening.
19. Aphakia in the Study Eye.
20. Prior vitrectomy in the Study Eye.
21. Prior intraocular or periocular steroids in the Study Eye.
22. Current vitreous hemorrhage or history of vitreous hemorrhage in the Study Eye within 3
months of Screening.
23. History of corneal transplant in the Study Eye.
5.2.2 General Exclusion Criteria
1. Women who are pregnant or lactating or intending to become pregnant during the study
2. Recent history (within the 6 months prior to screening) of myocardial infarction, stroke,
transient ischemic attack, acute congestive heart failure or any acute coronary event.
3. 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.
4. History of hypersensitivity to any component of KSI-301, aflibercept, ophthalmic dye
(fluorescein), dilating drops, or any of the anesthetic or antimicrobial preparations used
during the study, as assessed by the Investigator.
5. Participation in an investigational study within 30 days prior to the screening visit that
involved treatment with any investigational drug (excluding vitamins and minerals) or
device, except for non-therapeutic ophthalmic imaging devices.
24. Active cancer within the 12 months prior to Screening except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin cancer, and prostate cancer with a
Gleason score of <6 and stable prostate-specific antigen for >12 months.
25. Treatment with systemic anti-VEGF therapeutics within 90 days prior to Screening.
26. Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100
mmHg while at rest at Screening or on Day 1.
• If a participant’s initial blood pressure measurement exceeds these values, up to
two additional readings may be taken later the same day or on a different day
during the screening period. If a participant’s blood pressure is controlled by
antihypertensive medications, the participant must be on a stable medication
regimen continuously for 21 days prior to Day 1.

E.5 End points

E.5.1

Primary end point(s)

Mean change in BCVA from baseline (Day 1) to
Week 40, in Early Treatment Diabetic Retinopathy
Study (ETDRS) Letters.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint will be assessed using ETDRS data collected up to Week 40.

E.5.2

Secondary end point(s)

• Mean change in BCVA (ETDRS Letters) from baseline (Day 1) by visit over time.
• Proportion of participants who gain ≥5, ≥10 and ≥15 ETDRS letters from baseline
(Day 1) by visit over time.
• Proportion of participants who lose ≥5, ≥10 and ≥15 ETDRS letters from baseline
(Day 1) by visit over time.
• Proportion of participants with BCVA Snellen equivalent of 20/40 or better from baseline
(Day 1) over time.
• Proportion of participants with BCVA Snellen equivalent of 20/200 or worse from
baseline (Day 1) over time.
• Mean change in OCT CST from baseline (Day 1) to Week 40 and over time.
• Incidence of ocular and systemic AEs up to Week 44.
• Systemic anti-drug antibody status over time (in the ADA-evaluable population).
• Systemic pharmacokinetic profile (i.e., systemic exposure) over time (in the PK-evaluable population).

E.5.2.1

Timepoint(s) of evaluation of this end point

Key secondary endpoints will be assessed at Week 40 (for efficacy) or Week 44 (for safety)

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)

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

Hungary

Latvia

Poland

Slovakia

Spain

Czechia

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 is defined as the last follow-up visit of the last participant enrolled (i.e., the last enrolled participant’s final visit) or a Sponsor decision to terminate the study, whichever comes first.

A participant is considered to have completed the study if he/she has completed all phases of the study, including the Week 44 safety follow-up assessment.

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

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:

250

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

250

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

160

F.4.2.2

In the whole clinical trial

500

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)

All participants will return to standard of care treatment, at the discretion of their Treating Physician, after completion of their final follow-up visit or once they discontinue from the study prematurely. The Sponsor will not provide continued access to study treatment following the end of the study or the end of each participant’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

2021-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-08-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-04-06

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