ICH GCP - EU Clinical trials Registry - 2022-004078-53 (NL)-ICH GCP

Summary
EudraCT Number:	2022-004078-53
Sponsor's Protocol Code Number:	83403
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-08-21
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

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2022-004078-53

A.3

Full title of the trial

Specifying the anti-inflammatory effects of ziltivekimab with diverse imaging modalities and in-depth cellular phenotyping

Specificeren van de anti-inflammatoire effecten van ziltivekimab met behulp van verschillende beeldvorming modaliteiten en diepgaand cellulaire fenotypering

A.3.1

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

Impact of inflammation lowering on plaques and systemic inflammation

Impact van ontsteking verlaging op plaques en systemische ontsteking

A.3.2

Name or abbreviated title of the trial where available

SPIDER

A.4.1

Sponsor's protocol code number

83403

A.7

Trial is part of a Paediatric Investigation Plan

No

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Academic Medical Center (AMC), department of Internal Medicine
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Academic Medical Center (AMC), department of Internal Medicine
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Academic Medical Center (AMC)
B.5.2	Functional name of contact point	Department of Internal Medicine
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 9
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105 AZ
B.5.3.4	Country	Netherlands
B.5.6	E-mail	e.s.stroes@amsterdamumc.nl

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	Ziltivekimab
D.3.2	Product code	NA
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ziltivekimab
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB204133
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

- Plaque characteristics
- Systemic inflammation

- Plaque karakteristieken
- Systemische inflammatie

E.1.1.1

Medical condition in easily understood language

- Plaque features
- Inflammation

- Aderverkalking kenmerken
- Ontsteking

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

No

E.2 Objective of the trial

E.2.1

Main objective of the trial

To study whether ziltivekimab therapy reduces arterial wall inflammation as assessed by imaging, and reduces the systemic inflammatory tone as assessed by circulating monocytes, inflammatory biomarkers and proteomics.

Te onderzoeken of ziltivekimab therapie de arteriële wandontsteking vermindert onderzocht met beeldvorming, en of ziltivekimab de systemische ontstekingstoon vermindert wat wordt geanalyseerd in circulerende monocyten, ontstekingsbiomarkers en proteomics.

E.2.2

Secondary objectives of the trial

Imaging:
• Difference in PCAT (CCTA derived) after ziltivekimab treatment.
• Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA.
• Difference in 68Ga-DOTATATE SUVmax of bone marrow and spleen after treatment.
• Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment.

Inflammation and proteomics:
• The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.
• The mean percentage change in plasmatic proteins before and after ziltivekimab treatment.
• The impact of ziltivekimab on inflammation in plasma cytokine and chemokine levels.

Beeldvorming:
- Verschil in PCAT (CCTA afgeleid) na ziltivekimab behandeling.
- Correlatie tussen veranderingen in coronaire 68Ga-DOTATATE opname en anatomische plaqueveranderingen op CCTA.
- Verschil in 68Ga-DOTATATE SUVmax van beenmerg en milt na behandeling.
- Verschil in 68Ga-DOTATATE TBRmax van de aorta ascendens na behandeling.

Inflammatie en proteomics:
- De impact van ziltivekimab op monocyt fenotype in transendotheliale migratie (TEM) capaciteit en transcriptoom profiel.
- De gemiddelde procentuele verandering in plasmatische eiwitten voor en na behandeling met ziltivekimab.
- Het effect van ziltivekimab op ontsteking in plasma cytokine en chemokine waardes.

E.2.3

Trial contains a sub-study

No

E.3

Principal inclusion criteria

- Aged 50 years and older.
- Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
- Serum hsCRP level ≥2 mg/L.

- 50 jaar en ouder.
- Multi-vessel coronaire hartziekte (gedefinieerd als CAD-RADS ≥2).
- Serum hsCRP waarde ≥2 mg/L.

E.4

Principal exclusion criteria

- Coronary stents in situ.
- Chronic or recent (<1 month) (serious) infections and/or clinical signs of acute (serious) infection.
- History of severe auto-immune diseases, or other (severe) (recurrent or chronic) inflammatory disorders.
- Untreated latent tuberculosis, active hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) or C, human immunodeficiency virus (HIV) not on stable antiretroviral regimen

- Coronaire stents in situ.
- Chronische of recente (<1 maand) (ernstige) infecties en/of klinische tekenen van acute (ernstige) infectie.
- Geschiedenis van ernstige auto-immuunziekten, of andere (ernstige) (terugkerende of chronische) ontstekingsaandoeningen.
- Onbehandelde latente tuberculose, actieve hepatitis B (positief HBsAg en/of positief anti-HBc met detecteerbaar HBV DNA) of C, humaan immunodeficiëntievirus (HIV) zonder stabiel antiretroviraal regime.

E.5 End points

E.5.1

Primary end point(s)

The main outcome is the mean percentage change in coronary arteries target to background ratio (TBRmax) and monocyte activation marker protein expression between the treatment and placebo group, at the primary analysis time point of 20 weeks, compared to baseline.

De primaire uitkomst is de gemiddelde procentuele verandering in de TBRmax van de kransslagaders en de expressie van monocytenactiveringsmarkers en eiwitten tussen de behandelde en de placebogroep, op het primaire analysetijdstip van 20 weken, vergeleken met baseline.

E.5.1.1

Timepoint(s) of evaluation of this end point

22 weeks

22 weken

E.5.2

Secondary end point(s)

Imaging:
• Difference in PCAT (CCTA derived) after ziltivekimab treatment.
• Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA.
• Difference in 68Ga-DOTATATE SUVmax of bone marrow and spleen after treatment.
• Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment.

Inflammation and proteomics:
• The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.
• The mean percentage change in plasmatic proteins before and after ziltivekimab treatment.
• The impact of ziltivekimab on inflammation in plasma cytokine and chemokine levels.

Beeldvorming:
- Verschil in PCAT (CCTA afgeleid) na ziltivekimab behandeling.
- Correlatie tussen veranderingen in coronaire 68Ga-DOTATATE opname en anatomische plaqueveranderingen op CCTA.
- Verschil in 68Ga-DOTATATE SUVmax van beenmerg en milt na behandeling.
- Verschil in 68Ga-DOTATATE TBRmax van de aorta ascendens na behandeling.

Inflammatie en proteomics:
- De impact van ziltivekimab op monocyt fenotype in transendotheliale migratie (TEM) capaciteit en transcriptoom profiel.
- De gemiddelde procentuele verandering in plasmatische eiwitten voor en na behandeling met ziltivekimab.
- Het effect van ziltivekimab op ontsteking in plasma cytokine en chemokine waardes.
Omschrijving en inschatting van belasting en risico (indien van toepassing):

E.5.2.1

Timepoint(s) of evaluation of this end point

22 weeks

22 weken

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

No

E.6.2

Prophylaxis

No

E.6.3

Therapy

Yes

E.6.4

Safety

No

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

No

E.6.7

Pharmacodynamic

No

E.6.8

Bioequivalence

No

E.6.9

Dose response

No

E.6.10

Pharmacogenetic

No

E.6.11

Pharmacogenomic

No

E.6.12

Pharmacoeconomic

No

E.6.13

Others

No

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

No

E.7.1.1

First administration to humans

No

E.7.1.2

Bioequivalence study

No

E.7.1.3

Other

No

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

No

E.7.4

Therapeutic use (Phase IV)

No

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

No

E.8.1.2

Open

No

E.8.1.3

Single blind

No

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

No

E.8.1.6

Cross over

No

E.8.1.7

Other

No

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

No

E.8.2.2

Placebo

Yes

E.8.2.3

Other

No

E.8.2.4

Number of treatment arms in the trial

2

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

No

E.8.5

The trial involves multiple Member States

No

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

No

E.8.6.2

Trial being conducted completely outside of the EEA

No

E.8.7

Trial has a data monitoring committee

No

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

4

E.8.9.1

In the Member State concerned months

0

E.8.9.1

In the Member State concerned days

0

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

No

F.1.1.1

In Utero

No

F.1.1.2

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

No

F.1.1.3

Newborns (0-27 days)

No

F.1.1.4

Infants and toddlers (28 days-23 months)

No

F.1.1.5

Children (2-11years)

No

F.1.1.6

Adolescents (12-17 years)

No

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

20

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

20

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

No

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

No

F.3.3.1

Women of childbearing potential not using contraception

No

F.3.3.2

Women of child-bearing potential using contraception

No

F.3.3.3

Pregnant women

No

F.3.3.4

Nursing women

No

F.3.3.5

Emergency situation

No

F.3.3.6

Subjects incapable of giving consent personally

No

F.3.3.7

Others

No

F.4 Planned number of subjects to be included

F.4.1

In the member state

40

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)

None

Geen

G. Investigator Networks to be involved in the Trial

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

N.

Competent Authority Decision

Authorised

N.

Date of Competent Authority Decision

2023-08-22

N.

Ethics Committee Opinion of the trial application

Favourable

N.

Ethics Committee Opinion: Reason(s) for unfavourable opinion

N.

Date of Ethics Committee Opinion

2023-07-27

P. End of Trial
P.	End of Trial Status	Ongoing

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