Clinical Trials Register

Summary
EudraCT Number:	2020-004202-60
Sponsor's Protocol Code Number:	CER-001-SEP_AKI_01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-08-31
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004202-60

A.3

Full title of the trial

A RAndomized pilot study comparing short-term CER-001 infusions at different doses to prevent Sepsis-induced acute kidney injury

Studio pilota, randomizzato, per valutare l'efficacia di differenti dosaggi infusivi a breve termine di CER-001, per la prevenzione del danno renale acuto indotto da sepsi

A.3.1

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

Clinical trial in which people are allocated by chance to receive one of several clinical treatments, different doses, to prevent sepsis-induced acute kidney injury

Studio clinico in cui le diverse opzioni di trattamento vengono assegnate in modo casuale, per identificare l’intervallo di dosi efficaci del farmaco CER-001 nel prevenire il danno renale acuto secondario a sepsi.

A.3.2

Name or abbreviated title of the trial where available

RACERS STUDY

A.4.1

Sponsor's protocol code number

CER-001-SEP_AKI_01

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	CERENIS THERAPEUTICS
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Consorzio per Valutazioni Biologiche e Farmacologiche
B.5.2	Functional name of contact point	Servizio Regolatorio
B.5.3	Address:
B.5.3.1	Street Address	Via Luigi Porta, 14
B.5.3.2	Town/ city	Pavia
B.5.3.3	Post code	27100
B.5.3.4	Country	Italy
B.5.4	Telephone number	038225075
B.5.5	Fax number	0382536544
B.5.6	E-mail	ricercaclinica@cvbf.net

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	CER-001
D.3.2	Product code	[1383435-67-3]
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CER-001
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	8
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	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	CER-001
D.3.2	Product code	[1383435-67-3]
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CER-001
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	8
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 3
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	CER-001
D.3.2	Product code	[1383435-67-3]
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CER-001
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	8
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Sepsis due to intra-abdominal cavity infection or urosepsis

Sepsi secondaria a peritonite o urosepsi

E.1.1.1

Medical condition in easily understood language

Systemic inflammatory response syndrome (SIRS) due to intra-abdominal cavity bacterial infection or SIRS due to bacterial infection of the urogenital tract

Risposta infiammatoria sistemica (SIRS) conseguente a un’infezione batterica secondaria a peritonite o SIRS conseguente a un’infezione batterica del tratto urogenitale

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10073462
E.1.2	Term	Injection site allergic reaction
E.1.2	System Organ Class	100000004867

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 investigate whether the use of CER-001 at different doses in combination with standard of care (SOC) treatment is safe and effective

Verificare se l'impiego di CER-001 a differenti dosaggi in combinazione con il trattamento standard (SOC) sia sicuro ed efficace

E.2.2

Secondary objectives of the trial

- providing new potential strategy to treat septic patients;
- reducing the inflammatory response and preventing the progression to AKI.

- fornire una nuova potenziale strategia di trattamento per i pazienti settici;
- ridurre la risposta infiammatoria e prevenire la progressione ad AKI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or non-pregnant female adult =18 years of age at time of enrollment;
2. Patients affected by sepsis sustained by Gram negative bacteria (positive body fluid cultures and/or documented endotoxin activity) on antibiotic treatment
3. Meets Sepsis 3 criteria, defined as an acute increase of at least 2 points in SOFA score relative to the SOFA score upon admission;
4. Endotoxin level (EEA™) >0.6;
5. Signed and dated informed consent by the patient itself or by a legal representative.

1. Maschi o femmine, non in gravidanza, di età =18 anni alla data della firma del modulo di CI;
2. Pazienti con sepsi sostenuta da batteri Gram negativi (obiettivata tramite una coltura positiva e/o una documentata attività endotossica) in trattamento antibiotico;
3. Pazienti che hanno una sepsi di grado 3, definita come un incremento acuto di almeno 2 punti dell’indice SOFA rispetto al basale;
4. Livelli di EEA>0.6 volte il limite superiore del range di normalità;
5. Pazienti in grado di fornire un'accettazione volontaria alla partecipazione firmando il Modulo di consenso informato (CI); nel caso di impossibilità da parte del paziente a formulare un assenso allo studio, il CI dovrà essere firmato dal rappresentante legale/tutore;

E.4

Principal exclusion criteria

1. Patients weighing more than 100 kg;
2. Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal;
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m2);
4. Patients who have AKI and have received nephrotoxic drugs since hospital admission that are known to cause acute tubular necrosis (e.g., vancomycin, aminoglycosides, IV immunoglobulin, mannitol), or with a history of hypovolemic conditions (vomiting, diarrhea, bleeding).
5. Leukocytes<2.0×10^9;
6. Pregnancy or breast feeding;
7. Undergone organ transplantation during the past one year;
8. Anticipated transfer to another hospital, which is not a study site within 72 hours;
9. Terminally ill, including metastases or hematological malignancy, with a life expectancy less than 30 days (as assessed by the attending physician) or have been classified as "Do Not Resuscitate";
10. Previous history of end stage chronic organ failure(s);
11. Diagnosed with HIV;
12. Uncontrolled hemorrhage within the last 24 h;
13. History of drug hypersensitivity, including history of adverse reactions to radiocontrast agents.
14. Patients who have used an investigational drug or device within 30 days of the first dose of CER-001.

1. Pazienti con un peso superiore a 100 Kg;
2. Alanina transaminasi/aspartato transaminasi (ALT/AST) > 5 volte il limite superiore del range di normalità;
3. Stadio 4 di nefropatia cronica o soggetti in dialisi (estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m2);
4. Pazienti con insufficienza renale acuta che hanno ricevuto farmaci nefrotossici che causano necrosi tubulare acuta (vancomicina, aminoglicosidi, immunoglobulina IV, mannitolo) o pazienti con storia di ipovolemia (vomito, diarrea, episodi emorragici);
5. Leucociti <2.0×109;
6. Gravidanza o allattamento al seno;
7. Pazienti sottoposti a trapianto d’organo nell’ultimo anno;
8. Pazienti trasferiti da un altro ospedale che non è inserito nello studio nelle prime 72 ore dalla diagnosi;
9. Malati terminali, con metastasi o neoplasie ematologiche, con un'aspettativa di vita inferiore a 30 giorni (secondo la valutazione del medico curante) o che sono stati classificati come "Non rianimabili";
10. Insufficienza cronica d’organo allo stadio terminale;
11. Diagnosi di HIV;
12. Emorragia incontrollata nelle ultime 24h;
13. Nota ipersensibilità, incluse pregresse reazioni avverse ad agenti di radiocontrasto;
14. Pazienti che sono stati trattati con un altro farmaco sperimentale entro 30 giorni dalla prima dose di CER-001.

E.5 End points

E.5.1

Primary end point(s)

The co-primary end-points of the study are: 1. Determination of optimal dose of CER-001 in combination with standard of care based on safety. 2. Onset of AKI according to KDIGO criteria (serum creatinine in the first 6 hours >1.5–1.9 times baseline creatinine and/or urine output < 0.5 ml/kg/h for 6-12 hours; see Table 2) 3. Severity of AKI according to KDIGO (Stages 1, 2 or 3; see Table 2 for definitions).

Co-primary endpoints sono: 1. Definire il dosaggio ottimale di CER-001 in combinazione con terapie standard (standard of care, SOC) sulla base del profilo di rischio; 2. Insorgenza di insufficienza renale acuta in accordo ai criteri KDIGO (creatinina sierica > 1.5 - 1.9 volte il valore basale e/o diuresi < 0.5 ml/kg/h per 6-12 ore; 3. Severità dell’insufficienza renale acuta in accordo ai criteri KDIGO.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days from baseline

30 giorni dal basale

E.5.2

Secondary end point(s)

Mortality at Day 30; Change in endotoxin and IL-6 levels from baseline to Day 3, Day 6 and Day 9. Baseline will be defined as the last measurements taken prior to dosing on Day 1.; Change in the SOFA score(47) from baseline to Day 3, Day 6 and Day 9.; Changes to the key inflammatory markers (CRP, D-dimer, Ferritin, IL-8, GM-CSF, MCP 1 and TNF-a) from baseline to Day 3, Day 6 and Day 9.; Changes in AKI biomarkers.

Mortalità a 30 giorni; Valutazione della variazione dei livelli di endotossina e IL-6 dal basale al giorno 3, 6 e 9. Il bsale viene definito come l'ultima misurazine effettuata prima dell'assunzione del farmaco al giorno 1.; Valutazione del cambiamento dei criteri SOFA dal basale al giorno 3, 6 e 9.; Valutazione dell’inibizione della cascata infiammatoria (CRP, D-dimer, Ferritina, IL-8, GM-CSF, MCP 1 and TNF-a) dal basale al giorno 3, 6 e 9.; Valutazione del cambiamento dei biomarcatori per l’insufficienza renale acuta.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days; Day 3, 6 and 9; Day 3, 6 and 9; Day 3, 6 and 9; 30 days

30 giorni; Giorno 3,6 e 9; Giorno 3, 6 e 9; Giorno 3, 6 e 9; 30 giorni

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

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Terapia standard

Standard of care

E.8.2.4

Number of treatment arms in the trial

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

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

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:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2.2

In the whole clinical trial

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)

Not applicable

Non applicabile

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

2020-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-10-27

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