Clinical Trials Register

Summary
EudraCT Number:	2020-001745-40
Sponsor's Protocol Code Number:	COVID-SARI-001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-06-24
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

2020-001745-40

A.3

Full title of the trial

PILOT STUDY ON THE USE OF SARILUMAB IN PATIENTS WITH COVID-19 INFECTION

A.3.1

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

PILOT STUDY ON THE USE OF SARILUMAB IN PATIENTS WITH COVID-19 INFECTION

Studio pilota sull'utilizzo di sarilumab in pazienti con infezione da COVID-19

A.3.2

Name or abbreviated title of the trial where available

COVID-SARI-001

A.4.1

Sponsor's protocol code number

COVID-SARI-001

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	ASST FATEBENEFRATELLI SACCO
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	ASST Fatebenefratelli Sacco
B.5.2	Functional name of contact point	Dipartimento di Scienze Cliniche -
B.5.3	Address:
B.5.3.1	Street Address	Via G.B. Grassi 74
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20157
B.5.3.4	Country	Italy
B.5.4	Telephone number	0239042451
B.5.5	Fax number	0250319758
B.5.6	E-mail	agostino.riva@unimi.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	Kevzara
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi
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	Kevzara
D.3.2	Product code	[SAR153191]
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	Sarilumab
D.3.9.1	CAS number	1189541-98-7
D.3.9.2	Current sponsor code	SAR153191
D.3.9.4	EV Substance Code	EU/17/1196/003
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	200
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

Patients with COVID-19 infection

Pazienti con infezione da COVID-19

E.1.1.1

Medical condition in easily understood language

Patients with COVID-19 infection

Pazienti con infezione da COVID-19

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.1
E.1.2	Level	LLT
E.1.2	Classification code	10048847
E.1.2	Term	Lung infection NOS
E.1.2	System Organ Class	100000004862

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 evaluate the safety and clinical efficacy of sarilumab in adult patients hospitalized due to severe Covid-19 pneumonia based on the proportion of patients who show an improvement of the respiratory function, described as =30% decrease in oxygen requirement compared to baseline.

Valutare la sicurezza e l'efficacia clinica di sarilumab nei pazienti adulti ricoverati in ospedale a causa di una polmonite Covid-19 grave sulla base della percentuale di pazienti che mostrano un miglioramento della funzione respiratoria, descritto come una riduzione =30% dell'ossigeno richiesto rispetto al basale.

E.2.2

Secondary objectives of the trial

Potenziale efficacia di sarilumab nella polmonite Covid-19:
• Nei pazienti con febbre al basale, valutazione del tempo alla risoluzione della febbre, definita come temperatura corporea =36,6 ° C axilla, =37,8 ° C rettale o timpanica per almeno 48 ore senza antipiretici;
• Valutazione della carica virale, sangue ed espettorato per COVID-19 prima della somministrazione di sarilumab, 48 ore e 96 ore dopo la somministrazione;
• Valutazione della concentrazione plasmatica di Il-6, TNF-a, Il-10 e GM-CSF pre-trattamento e 96 e 120 ore dopo il trattamento;
• Valutazione del tasso di progressione della frazione WBC di granulociti immaturi - IG - (conteggi assoluti e%) e dei parametri morfologici-funzionali definiti da:
- complessità citoplasmatica
- intensità di fluorescenza
- dimensioni
- ampiezza di distribuzione degli eventi su entrambi gli assi del citogramma WDF.

Further investigate the potential effectiveness of sarilumab in Covid-19 pneumonia by means of:
• In patients with fever at baseline, evaluation of the time to resolution of fever, defined as body temperature =36.6°C axilla, =37.8°C rectal or tympanic for at least 48 hours without antipyretics;
• Evaluation of the viral load on blood and sputum for COVID-19 before administration of sarilumab, 48 hours and 96 hours after administration;
• Evaluation of the plasma concentration of Il-6, TNF-a, Il-10, and GM-CSF pre-treatment and 96 and 120 hours post-treatment;
• Evaluation of the rate of progression of WBC fraction of immature granulocytes - IG - (absolute and % counts) and the morphological-functional parameters defined by:
o cytoplasmic complexity
o fluorescence intensity
o size
o distribution magnitude of events on both axes of the WDF cytogram.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age = 18 years and < 85 years.
• Documented (chest X-Ray or TC scan), severe (BCRSS =3 and <4) interstitial pneumonia with respiratory failure (requiring supplemental oxygen) with positive Covid-19 swab testing.
• Worsening of respiratory exchanges such as to require ventilation with Venturi mask >31% (6L/minute).
• Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching = 1000 ng/mL.
• Signed informed consent

• Età = 18 anni e <85 anni.
• Documentata (radiografia del torace o TC), polmonite interstiziale grave (BCRSS =3 e <4) con insufficienza respiratoria (che richiede ossigeno supplementare) con test di tampone Covid-19 positivo.
• Necessità di una ventilazione con maschera Venturi> 31% (6L / minuto).
• Livelli aumentati di D-dimero (> 1500 ng / mL) o D-dimero che aumentano progressivamente (oltre 3 misurazioni consecutive) e raggiungono = 1000 ng / mL.
• Consenso informato firmato.

E.4

Principal exclusion criteria

• Age < 18 years or = 85 years.
• AST / ALT > 5x ULN.
• Neutrophil count lower than 500 cells / mL.
• PTL count lower than 50,000 cells / mL.
• Documented sepsis due to infections other than Covid-19.
• Presence of serious co-morbidities (such as COPD, diabetes, or cardiomyopathies) likely to cause, according to the clinical judgment, an unfavorable outcome.
• Complicated diverticulitis or intestinal perforation.
• Immunosuppressive therapy due to organ transplant.

• Età <18 anni o = 85 anni.
• AST / ALT> 5x ULN.
• Conta dei neutrofili inferiore a 500 cellule / mL.
• Conteggio PTL inferiore a 50.000 cellule / mL.
• Sepsi documentata dovuta a infezioni diverse da Covid-19.
• Presenza di gravi comorbilità (come BPCO, diabete o cardiomiopatie) che possono causare, secondo il giudizio clinico, un risultato sfavorevole.
• Diverticolite complicata o perforazione intestinale.
• Terapia immunosoppressiva dovuta al trapianto di organi.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients who show an improvement of the respiratory function, described as =30% decrease in oxygen requirement compared to baseline.

Percentuale di pazienti che mostrano un miglioramento della funzione respiratoria, descritto come una riduzione =30% dell'ossigeno richiesto rispetto al basale.

E.5.1.1

Timepoint(s) of evaluation of this end point

Daily until discharge

Giornalmente fino a dimissione

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

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

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

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

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

unconscious patients may be included

Potrebbero essere inclusi anche pazienti incoscienti

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)

Patients will be treated according to local clinical practice or guidelines on COVID-19 disease

I pazienti saranno trattati in accordo alla pratica clinica locale o alle linee guida per la malattia COVID-19

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

2020-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-23

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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