Clinical Trials Register

Summary
EudraCT Number:	2020-001185-11
Sponsor's Protocol Code Number:	BREATH
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:	2020-08-10
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

2020-001185-11

A.3

Full title of the trial

A proof-of concept study of the use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the treatment of COVID-19-related pneumonia: a two-step phase II clinical trial

Baricitinib per la polmonite da Corona virus: sperimentazione terapeutica

A.3.1

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

Baricitinib for coRona virus pnEumonia: a THerapeutic trial (BREATH trial)

Baricitinib per la polmonite da Corona virus: sperimentazione terapeutica

A.3.2

Name or abbreviated title of the trial where available

BREATH Trial

A.4.1

Sponsor's protocol code number

BREATH

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	FONDAZIONE I.R.C.C.S. POLICLINICO SAN MATTEO
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	Fondazione IRCCS Policlinico San Matteo
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Policlinico San Matteo
B.5.2	Functional name of contact point	U.O.C. Reumatologia
B.5.3	Address:
B.5.3.1	Street Address	Piazzale Golgi 19
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	3491874209
B.5.6	E-mail	sara.saramonti@gmail.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	Yes
D.2.1.1.1	Trade name	Baricitinib
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	Baricitinib
D.3.2	Product code	[---]
D.3.4	Pharmaceutical form	Film-coated tablet
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	Baricitinib
D.3.9.1	CAS number	1187594-09-7
D.3.9.2	Current sponsor code	Baricitinib
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	4
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	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.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	Yes
D.2.1.1.1	Trade name	Baricitinib
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	Baricitinib
D.3.2	Product code	[---]
D.3.4	Pharmaceutical form	Film-coated tablet
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	Baricitinib
D.3.9.1	CAS number	1187594-09-7
D.3.9.2	Current sponsor code	Baricitinib
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	2
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	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

Covid-19 infection

Infezione Covid-19

E.1.1.1

Medical condition in easily understood language

Covid-19 infection

Infezione 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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy and safety of Baricitinib in the management of patients admitted for COVID-19 pneumonia

Valutare l’efficacia e la sicurezza di Baricitinib nel trattamento dei pazienti con polmonite nel contesto di COVID-19

E.2.2

Secondary objectives of the trial

1. To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days
2. To quantify the mortality within 8 days
3. Peripheral capillary oxygen saturation (SpO2)
4. PaO2/FiO2
5. To assess the rate of patients admitted to the ICU
6. To measure the length of hospital stay
7. To quantify 28-day mortality
8. To quantify the rate of re-admission within 28 days
9. To quantify the cumulative incidence and severity of adverse events

1. Quantificare il tasso di ciascuno tra: alterazione moderata (100<PaO2/FiO2<=200) o severa (PaO2/FiO2<=100) dell’ossigenazione entro 8 giorni
2. Quantificare la mortalità entro 8 giorni
3. Saturazione periferica (SpO2)
4. PaO2/FiO2
5. Valutare il tasso di pazienti ricoverati in ICU
6. Misurare la durata della degenza
7. Quantificare la mortalità a 28 giorni
8. Quantificare il tasso di ulteriore ricovero entro 28 giorni
9. Quantificare l’incidenza cumulativa e la severità degli eventi avversi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib’s efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection
- informed Consent as documented by signature
- patients with a confirmed SARS-CoV-2 pneumonia
- adult patients aged 18-74 years old
- infiltrates at chest radiography
- = 48 hours from admission
- c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L
- Lymphocyte count less than 1500/mmc
- 200 < PaO2/FiO2 = 300

Pazienti adulti (18-74 anni) con diagnosi confermata di polmonite con SARS-CoV-2 con infiltrati alla radiografia del torace e con fattori di attivazione flogistica sistemica insorti o peggiorati nonostante la terapia standard ad almeno 48 ore dalla prima valutazione.

E.4

Principal exclusion criteria

- 18 years old< age <= 75 years old
- concomitant bacterial infection
- lymphopenia less than 200/mmc
- hemoglobin < 8 g/dl
- absolute neutrophil count < 1 x 109 cells/L
- requiring continuous positive airway pressure (C-PAP) or mechanical ventilation
- sudden clinical deterioration requiring ICU access or palliative care

Exclusion criteria (Drug-related)
- known hypersensitivity or allergy to the study drug
- Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily
- Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment)
- Pregnant or breast-feeding
- Active tuberculosis
- Evidence of active HBV (HbsAg positive) or with detectable HCV-RNA, HIV
- Ongoing, acute diagnosis of DVT/PE
- Previous diagnosis of DVT/PE

- 18 anni< età <=75 anni
- Infezione batterica concomitante
- Linfopenia < 200/mmc
- Emoglobina < 8 g/dl
- Conta assoluta dei neutrofili < 1 x 109 cellule/L
- Necessità di ventilazione con pressione positiva continua (c-PAP) o ventilazione meccanica
- Deterioramento clinico improvviso richiedente l’accesso in terapia intensiva o cure palliative

Criteri di esclusione (legati al farmaco):
- Nota ipersensibilità o allergia al farmaco sperimentale
- Clearance della creatinina < 30 mL/min; se la clearance della creatinina è tra 30 e 60 mL/min, la dose di Baricitinib dovrà essere ridotta a 2 mg/die
- Compromissione epatica severa (non è necessario un aggiustamento della dose di Baricitinib in caso di alterazione lieve o moderata)
- In stato di gravidanza o di allattamento
- Tubercolosi attiva
- Evidenza di infezione attiva da HBV (HbsAg positività) o con HCV-RNA rilevabile, HIV
- Diagnosi di trombosi venosa profonda/embolia polmonare acuta in corso
- Precedente diagnosi di DVT/PE

E.5 End points

E.5.1

Primary end point(s)

The primary outcome of the study will be the response to treatment. A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria (24) or death, whichever occurs first, within 8 days from enrolment.

La risposta al trattamento. Un paziente viene considerate come responsivo in assenza di un’alterazione moderata o severa dell’ossigenazione (misurata con il rapporto PaO2/FiO2 all’emogas-analisi arteriosa) ed in mancanza di morte, sulla base dell’evento che si verificherà per primo, entro 8 giorni dall’arruolamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

8 days

8 giorni

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

8 and 28 days

8 e 28 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

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-08-10.

Yes

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

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 continuously monitored daily until the resolution of COVID-19 infection, or the occurrence of death

I pazienti verranno monitorati fino alla risoluzione dell'infezione da Covid-19 o alla morte

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

2020-05-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-30

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

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