Clinical Trials Register

Summary
EudraCT Number:	2020-000942-32
Sponsor's Protocol Code Number:	IZD334-002
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-06-10
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

Netherlands - Competent Authority

A.2

EudraCT number

2020-000942-32

A.3

Full title of the trial

A 12-week, multi-center, double-blinded, parallel-group, randomized, placebo-controlled phase IIb study to evaluate the safety, tolerability and efficacy of IZD334 to reduce CRP in cardiovascular high-risk patients

A.3.1

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

A study investigating the safety, tolerability and efficacy of IZD334 in patients with high cardiovascular risk

A.4.1

Sponsor's protocol code number

IZD334-002

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	Inflazome Ireland Ltd.
B.1.3.4	Country	Ireland
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	Inflazome Ltd.
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Inflazome UK Ltd.
B.5.2	Functional name of contact point	Director Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Unit 6 Grain House, Mill Court, Great Shelford
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB22 5LD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+41792025755
B.5.6	E-mail	c.berger@inflazome.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	IZD334
D.3.2	Product code	IZD334
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	selective NLRP3 inhibitor
D.3.9.1	CAS number	2260969-36-4
D.3.9.2	Current sponsor code	IZD334
D.3.9.3	Other descriptive name	IZD334
D.3.9.4	EV Substance Code	SUB207117
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	54.85
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.IMP: 2
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	IZD334
D.3.2	Product code	IZD334
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	selective NLRP3 inhibitor
D.3.9.1	CAS number	2260969-36-4
D.3.9.2	Current sponsor code	IZD334
D.3.9.3	Other descriptive name	IZD334
D.3.9.4	EV Substance Code	SUB207117
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	164.55
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	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with stable coronary artery disease and high cardiovascular risk

E.1.1.1

Medical condition in easily understood language

Patients with high cardiovacular risk

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

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	10011078
E.1.2	Term	Coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac 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

• Investigate the safety and tolerability of oral IZD334 in patients with high cardiovascular risk
• Evaluate the percent change from baseline of 450mg IZD334 compared to placebo in plasma C-reactive protein (CRP) after 12 weeks of treatment

E.2.2

Secondary objectives of the trial

• Evaluate the percent change from baseline of 150mg IZD334 compared to placebo in plasma CRP after 12 weeks of treatment
• Evaluate the percent change from baseline of 50mg IZD334 compared to placebo in plasma CRP after 12 weeks of treatment
• Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 450mg IZD334 compared to placebo after 12 weeks of treatment
• Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 150mg IZD334 compared to placebo after 12 weeks of treatment
• Evaluate the percentage of participants achieving a reduction from baseline in plasma CRP to <2 mg/L with 50mg IZD334 compared to placebo after 12 weeks of treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed and dated informed consent form obtained before any study assessment is performed
2. Male or female patients aged ≥18 years
3. Stable coronary artery disease (CAD) where stable coronary artery disease refers to any of the following:
a. a reversible supply/demand mismatch related to ischemia or
b. a history of myocardial infarction (minimum 30 days prior to
randomization) or
c. the presence of coronary artery plaque of any severity
documented by cardiac catheterization or computed tomography angiography.
Patients are considered stable if they are asymptomatic or their symptoms are adequately controlled by medications or revascularization.
4. Elevated plasma CRP level of ≥ 2 mg/L at screening visit 1 (local lab) and confirmed at screening visit 2 by central lab
5. Negative pregnancy test for females of child-bearing potential (premenopausal, ˂ 2 years post-menopausal, not surgically sterile)
6. Stable concomitant medication for at least 4 weeks prior to randomization
7. Patients with creatinine clearance ˃ 30 mL/min/1.73m2 by the MDRD (modification of diet in renal disease) equation may be included

E.4

Principal exclusion criteria

1. Any use of NSAIDs or steroids or cholchicine or anti-IL-1 inhibitors within 4 weeks prior to randomization (ASS 100mg as part of SOC treatment is allowed / topical, inhaled, local steroid use in doses that are not considered to cause systemic effects are permitted)
2. Any investigational drugs or participation in a clinical trial within 4 weeks or five half-lives (whichever is longer) prior to randomization
3. Active systemic infections (other than common cold) during the two weeks prior to randomization
4. Positive test for hepatitis B virus surface antigen (HBsAg) or Hepatitis C virus RNA at screening
5. Positive test for HIV at screening
6. History of severe hypersensitivity according to the investigator’s judgement to previous drugs of similar chemical classes
7. Any severe, progressive or uncontrolled medical condition at baseline that in the judgment of the investigator prevents the patient from participating in the study including uncontrolled hypertension, uncontrolled diabetes and severe hepatic disease
8. Symptomatic patients with Class IV heart failure (HF) (New York Heart Association)
9. Planned Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Grafting (CABG)
10. Any clinically significant abnormal laboratory tests at screening
11. A history of alcohol and/or substance abuse that could interfere with the conduct of the trial
12. Inability or unwillingness to undergo repeated venipunctures (e.g., due to poor tolerability or lack of access to veins)
13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (HCG) laboratory test (> 5 mIU/mL)
14. Women of childbearing potential unwilling or unable to practice effective method of contraception

E.5 End points

E.5.1

Primary end point(s)

Mean change in CRP at 12 weeks of 450mg IZD334 compared to placebo

E.5.1.1

Timepoint(s) of evaluation of this end point

At Week 12 (End of treatment visit)

E.5.2

Secondary end point(s)

• Measurement of reduction of CRP in % from baseline to week 12 of 150mg IZD334 treatment
• Measurement of reduction of CRP in % from baseline to week 12 of 50mg IZD334 treatment
• Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 450mg IZD334 treatment
• Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 150mg IZD334 treatment
• Determination of % of patients achieving a reduction of plasma CRP < 2mg/L from baseline to week 12 of 50mg IZD334 treatment
• Determination of other inflammatory biomarkers at week 12 compared to baseline as markers for elevated risk for MACE. The following biomarkers are investigated: IL-6, IL-18, caspase-1, IL-1b, ASC and TNFa

E.5.2.1

Timepoint(s) of evaluation of this end point

At Week 12 (End of treatment visit)

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

• Evaluation of biomarkers levels in plasma (such as IL-6 IL-1b, IL-18, ASC, caspase-1, NLRP3 and TNFα)
• Exploring markers of cardiac damage, glucose and lipid metabolism
• Exploring responder analysis based on IL-1b genetic pattern

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)

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)

E.8.2.2

Placebo

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LPLV

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

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:

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

132

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

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

2020-06-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-10-07

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