Clinical Trials Register

Summary
EudraCT Number:	2021-003273-66
Sponsor's Protocol Code Number:	ENX-CL-02-002
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-09-15
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

Greece - EOF

A.2

EudraCT number

2021-003273-66

A.3

Full title of the trial

A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

Μελέτη Φάσης 2, Πολυκεντρική, Τυχαιοποιημένη, Ελεγχόμενη με Εικονικό Φάρμακο Προσδιορισμού Δόσης , για την Αξιολόγηση της Αποτελεσματικότητας, Ασφάλειας και Ανεκτικότητας σε Διαφορετικές Δόσεις και Σχήματα του Allocetra-OTS για τη Θεραπεία της Οργανικής Ανεπάρκειας σε Ενήλικες Ασθενείς με Σήψη

A.3.1

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

Phase 2 study, conducted in few medical centers, patients will be allocated randomly to receive active drug or placebo. The study will evaluate the efficacy and safety of different doses of the drug in patients with organ failure due to sepsis condition.

Μελέτη φάσης 2 που θα πραγματοποιηθεί σε λίγα ιατρικά κέντρα, οι ασθενείς θα κατανεμηθούν τυχαία και θα λάβουν το φάρμακο της μελέτης ή εικονικό φάρμακο. Η μελέτη θα αξιολογήσει την αποτελεσματικότητα και την ασφάλεια του φαρμάκου σε ασθενείς με οργανική ανεπάρκεια λόγω Σήψης.

A.4.1

Sponsor's protocol code number

ENX-CL-02-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04612413

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	Enlivex Therapeutics R&D Ltd.
B.1.3.4	Country	Israel
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	Enlivex Therapeutics R&D Ltd.
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Accelsiors CRO and Consultancy Services Ltd.
B.5.2	Functional name of contact point	Regulatory unit
B.5.3	Address:
B.5.3.1	Street Address	103 Háros Str
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1222
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3612990091
B.5.5	Fax number	+3812165 03 380
B.5.6	E-mail	regulatory@accelsiors.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	Allocetra-OTS cells in Ringer's Lactate Solution
D.3.4	Pharmaceutical form	Solution for 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.3.8	INN - Proposed INN	Allogeneic peripheral blood mononuclear cells induced to apoptotic state
D.3.9.2	Current sponsor code	Allocetra-OTS
D.3.9.3	Other descriptive name	Allogeneic peripheral blood mononuclear cells induced to an early apoptotic state
D.3.9.4	EV Substance Code	SUB199514
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5000000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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	Allocetra-OTS cells in Ringer's Lactate Solution
D.3.4	Pharmaceutical form	Solution for 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.3.8	INN - Proposed INN	Allogeneic peripheral blood mononuclear cells induced to apoptotic state
D.3.9.2	Current sponsor code	Allocetra-OTS
D.3.9.3	Other descriptive name	Allogeneic peripheral blood mononuclear cells induced to apoptotic state
D.3.9.4	EV Substance Code	SUB199514
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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 infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sepsis

Σήψη

E.1.1.1

Medical condition in easily understood language

Sepsis is a life-threatening, medical emergency caused by an infection in the blood stream that can affect different organs.

Η σήψη είναι μια απειλητική για τη ζωή, ιατρική κατάσταση έκτακτης ανάγκης που προκαλείται από λοίμωξη στο αίμα που μπορεί να επηρεάσει πολλαπλά όργανα στον οργανισμό.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10040047
E.1.2	Term	Sepsis
E.1.2	System Organ Class	10021881 - Infections and infestations

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 compare the safety and efficacy of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients

Η σύγκριση της ασφάλειας και της αποτελεσματικότητας διαφορετικών δόσεων και θεραπευτικών σχημάτων του Allocetra-OTS με αντίστοιχα του εικονικού φαρμάκου για τη θεραπεία της οργανικής ανεπάρκειας σε ενήλικες ασθενείς με σήψη

E.2.2

Secondary objectives of the trial

To compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients and assess long term safety follow up

Η σύγκριση άλλων κλινικών εκδηλώσεων διαφορετικών δόσεων και θεραπευτικών σχημάτων του Allocetra-OTS που σχετίζονται με την οργανική ανεπάρκεια σε ενήλικες ασθενείς με σήψη και η αξιολόγηση της μακροπρόθεσμης παρακολούθησης ασφαλείας

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Suspected, presumed or documented community-acquired pneumonia by imaging.
2. Meets Sepsis 3 criteria: the presence of organ dysfunction as identified by a total SOFA score ≥2 points above pre-admission SOFA.

1. Εικαζόμενη, πιθανολογούμενη ή τεκμηριωμένη πνευμονία της κοινότητας μέσω απεικόνισης.
2. Πληροί τα κριτήρια Σήψης 3: η παρουσία οργανικής δυσλειτουργίας όπως προσδιορίζεται από συνολικό SOFA σκορ ≥2 βαθμών από το SOFA σκορ προ της εισαγωγής.

E.4

Principal exclusion criteria

1. Invasive ventilated patient and PaO2/FiO2 < 100 mmHg
2. SOFA score ≥ 10 at screening (Day -1).
3. Patients with septic shock; requiring persisting hypotension treated with vasopressors to maintain MAP ≥65 mmHg AND having a serum lactate level >4 mmol/L (36 mg/dL) despite adequate volume resuscitation at screening and on Day 1 prior to IP administration
4. Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or chronic viral infections, such as, hepatitis B virus (HBV) or hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other chronic infections.
5. Chronic respiratory disease requiring home oxygen therapy on a regular basis for > 6 h/day.

1. Ασθενής με επεμβατικό αερισμό και PaO2/FiO2 < 100 mmHg
2. Σκορ SOFA ≥ 10 κατά τη διαλογή (Ημέρα -1).
3. Ασθενείς με Σηπτικό σοκ, για το οποίο απαιτείται επίμονη υπόταση υπό θεραπεία με αγγειοσυσπαστικά για τη διατήρηση της MAP ≥65 mmHg ΚΑΙ με γαλακτικό ορό > 4 mmol/L (36 mg/dL) παρά την επαρκή αποκατάσταση όγκου κατά τη διαλογή και την Ημέρα 1 πριν από την χορήγηση του ΥΕΠ.
4. Γνωστές ενεργές λοιμώξεις κορονοϊού που προκαλεί σοβαρό οξύ αναπνευστικό σύνδρομο τύπου 2 (SARS-CoV-2) ή χρόνιες ιογενείς λοιμώξεις, όπως ιός ηπατίτιδας Β (HBV) ή ο ιός ηπατίτιδας C (HCV), ο ιός της ανθρώπινης ανοσοανεπάρκειας (HIV) ή άλλες χρόνιες λοιμώξεις.
5. Χρόνια αναπνευστική νόσος για την οποία χρειάζεται οξυγονοθεραπεία στο σπίτι σε τακτική βάση για > 6 ώρες/ημέρα.

E.5 End points

E.5.1

Primary end point(s)

Efficacy: Change from baseline in SOFA score throughout 28 days.
Safety: Number and severity of AEs and Serious Adverse Events (SAEs) throughout 28 days follow up period.

Αποτελεσματικότητα: Μεταβολή από την τιμή αναφοράς στο SOFA σκορ καθ‘ όλη τη διάρκεια των 28 ημερών.
Ασφάλεια: Αριθμός και βαρύτητα των Ανεπιθύμητων Συμβάντων(ΑΣ) και των Σοβαρών Ανεπιθύμητων Συμβάντων (ΣΑΣ) καθ‘ όλη τη διάρκεια της περιόδου παρακολούθησης των 28 ημερών.

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days

28 ημέρες

E.5.2

Secondary end point(s)

Ventilator-free days over 28 days
Vasopressor-free days over 28 days
All-cause mortality at Day 28 following first dose
Days without renal replacement therapy (dialysis) (evaluation up to 12 months)
Time in ICU and time in hospital (evaluation up to 12 months)
Number of days with creatinine ≤ Baseline levels +20% (evaluation up to 12 months)
Changes from baseline in C-reactive protein (CRP) levels (evaluation up to 12 months)
Detection of autoimmune and human leukocyte antigen (HLA) antibodies (evaluation up to 12 months)
Number and severity of AEs and SAEs throughout 12 months follow-up period (evaluation up to 12 months)

• Αριθμός Ημερών χωρίς αναπνευστήρα κατά τις 28 ημέρες
• Αριθμός Ημερών χωρίς αγγειοσυσπαστικά κατά τις 28 ημέρες
• Αριθμός Ημερών χωρίς θεραπεία νεφρικής υποκατάστασης (αιμοκάθαρση)
• Χρόνος στη ΜΕΘ και χρόνος νοσηλείας
• Αριθμός ημερών με κρεατινίνη ≤ Επίπεδα αναφοράς +20%
• Θνησιμότητα από κάθε αιτία την Ημέρα 28 μετά την πρώτη δόση
• Μεταβολές από την τιμή αναφοράς στα επίπεδα C-αντιδρώσας πρωτεΐνης (CRP)
• Αριθμός και βαρύτητα των ΑΣ και ΣΑΣ καθ’ όλη τη διάρκεια της περιόδου παρακολούθησης 12 μηνών
• Ανίχνευση αυτοάνοσων και αντισωμάτων ανθρώπινων αντιγόνων λευκοκυττάρων (HLA)

E.5.2.1

Timepoint(s) of evaluation of this end point

28 days and throughout 12 months follow-up period

28 και καθ’ όλη τη διάρκεια παρακολούθησης 12 μηνών

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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

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

Israel

Spain

Germany

Greece

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

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

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Some subjects may be in a medical condition where they cannot give consent. Legal rep. may provide consent on their behalf, or a delayed consenting will be performed, in a matter that fully complies with local competent authority requirements.

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

160

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)

No additional treatment or follow up is planned following study end.

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

2021-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-21

P. End of Trial
P.	End of Trial Status	Completed

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