Clinical Trials Register

Summary
EudraCT Number:	2020-001513-20
Sponsor's Protocol Code Number:	DEFI-VID19
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:	2020-06-24
Trial results	View 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

2020-001513-20

A.3

Full title of the trial

Use of Defibrotide to reduce progression of acute respiratory failure rate in
patients with COVID-19 pneumonia

Uso di Defibrotide in infusione intravenosa per ridurre la progressione dell'insufficienza respiratoria in pazienti con polmonite severa da COVID-19

A.3.1

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

Use of Defibrotide to reduce progression of acute respiratory failure rate in
patients with COVID-19 pneumonia

Uso di Defibrotide in infusione intravenosa per ridurre la progressione dell'insufficienza respiratoria in pazienti con polmonite severa da COVID-19

A.3.2

Name or abbreviated title of the trial where available

Defibrotide in COVID19

A.4.1

Sponsor's protocol code number

DEFI-VID19

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04335201

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	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Ospedale San Raffaele
B.5.2	Functional name of contact point	URC-SCP
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.4	Telephone number	0226434289
B.5.6	E-mail	urc.scp@hsr.it

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	Yes
D.2.1.1.1	Trade name	DEFITELIO - 80 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) 2,5 ML - 10 FLACONCINI
D.2.1.1.2	Name of the Marketing Authorisation holder	GENTIUM S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Defibrotide
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for 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	DEFIBROTIDE (DI ORIGINE SUINA)
D.3.9.2	Current sponsor code	NA
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	80
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe COVID-19 pneumonia

Polmonite severa da COVID-19

E.1.1.1

Medical condition in easily understood language

Severe COVID-19 pneumonia

Polmonite severa da COVID-19

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	PT
E.1.2	Classification code	10051905
E.1.2	Term	Coronavirus infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10035737
E.1.2	Term	Pneumonia viral
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 demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia

Dimostrare che la somministrazione di Defibrotide per via endovenosa in pazienti con polmonite da COVID-19 é in grado di ridurre la progressione della insufficienza respiratoria, l’evoluzione verso intubazione orotracheale e ventilazione meccanica

E.2.2

Secondary objectives of the trial

• To evaluate the safety of Defibrotide in the cohort of patients treated (incidence of adverse events)
• To evaluate the duration of hospitalization for patients enrolled
• To evaluate the overall survival at day+28 after start treatment with Defibrotide
• To evaluate the change in biological features of systemic inflammation (PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3) at day +7 and +14 after start of treatment with Defibrotide

• Valutare la safety di Defibrotide e l’incidenza di reazioni avverse
• Valutare la sopravvivenza globale a giorno+28 e dall'inizio del trattamento
• Valutare la durata complessiva del ricovero
• Valutare l’evoluzione dei parametri biologici di infiammazione sistemica a giorno+7 e +14 dall'inizio del trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Documented COVID-19 pneumonia: defined as upper respiratory tract swab positive for COVID-19 and/or imaging at computed tomography scan
suggestive of COVID-19 pneumonia
• SaO2 of 92% or less without oxygen support, or reduction of 3% from basal value of SaO2, or a ratio of PaO2/FiO2 below 300.
• Any gender
• Age >= 18 years
• Written informed consent or as per Ethical Committee indication in case of patients not able to express written informed consent

• Diagnosi di polmonite COVID-19: tampone virale positivo e/o imaging e clinica compatibile in assenza di altre documentate diagnosi
• SpO2 <=92% in aria ambiente o variazione SpO2 di 3 punti percentuali in meno rispetto al basale o P/F = 300
• Età>=18 anni
• Consenso informato o come da indicazioni del CE in caso di pazienti sedati o con sensorio obnubilato

E.4

Principal exclusion criteria

• Onset of COVID-19 pneumonia >14 days
• Orotracheal intubation
• Uncontrolled systemic infection (other than COVID-19)
• Concomitant use of thrombolytic therapy or systemic anticoagulant therapy
• Haemodynamic instability, defined as inability to maintain mean arterial pressure with single pressor support
• Hypersensitivity to the active substance or to any of the excipients of the experimental drug
• Patients who, based on the investigator's clinical judgement, are not able to receive the treatment
• Pregnancy or breastfeeding patient

• Polmonite da COVID-19 insorta da oltre 14 giorni
• Paziente intubato
• Evidenza di infezione non controllata (esclusa l’infezione da SARS-CoV-2)
• Terapia anticoagulante o antitrombotica in corso
• Altra controindicazione medica/di opportunità espressa dal curante
• Ipersensibilità al farmaco in studio o ai suoi eccipienti
• Intabilità emodinamica, necessitante supporto farmacologico
• Gravidanza o allattamento

E.5 End points

E.5.1

Primary end point(s)

Respiratory-failure rate (RFR)

Riduzione della progressione dell’insufficienza respiratoria acuta

E.5.1.1

Timepoint(s) of evaluation of this end point

14 days from treatment start

14 giorni dall'inizio del trattamento

E.5.2

Secondary end point(s)

Adverse event; Duration of hospitalization; Systemic inflammation; Overall survival

Eventi avversi; Durata del ricovero; Infiammazione sistemica; Sopravvivenza globale

E.5.2.1

Timepoint(s) of evaluation of this end point

7 days from treatment start; 14 days from treatment start; 7 days and 14 days from treatment start; 28 days from treatment start

7 giorni dall'inizio del trattamento; 14 giorni dall'inizio del trattamento; 7 e 14 giorni dall'inizio del trattamento; 28 giorni dall'inizio del trattamento

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

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Con coorte osservazionale di riferimento

With a parallel retrospective collection of data on not treated patients

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

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

Information not present in EudraCT

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

Sedated patients

Pazienti sedati o con sensorio obnubilato

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)

Normal clinical practice

Normale pratica clinica

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

2020-04-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-06

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

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