Clinical Trials Register

Summary
EudraCT Number:	2020-003872-42
Sponsor's Protocol Code Number:	ANTIICIPATE
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:	2020-11-23
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

2020-003872-42

A.3

Full title of the trial

Antiviral and Immunomodulatory Interferon-Beta in high-risk COVID-19 patients

Valutazione dell’attività antivirale e immunomodulatoria di Interferone-Beta in pazienti COVID-19 anziani

A.3.1

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

Antiviral and Immunomodulatory Interferon-Beta in high-risk COVID-19 patients

Valutazione dell’attività antivirale e immunomodulatoria di Interferone-Beta in pazienti COVID-19 anziani

A.3.2

Name or abbreviated title of the trial where available

ANTIICIPATE

A.4.1

Sponsor's protocol code number

ANTIICIPATE

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	Istituto di Farmacologia Traslazionale - CNR
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	Regione Lazio
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Istituto Nazionale per le malattie infettive "Lazzaro Spallanzani"
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Merck Healthcare KGaA
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Istituto Superiore di Sanità
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Istituto di Farmacologia Traslazionale - CNR
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	Istituto di Farmacologia Traslazionale - CNR
B.5.2	Functional name of contact point	Steering committee dello studio ANT
B.5.3	Address:
B.5.3.1	Street Address	via fosso del cavaliere
B.5.3.2	Town/ city	100
B.5.3.3	Post code	00133
B.5.3.4	Country	Italy
B.5.6	E-mail	filippo.belardelli@ift.cnr.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	REBIF - 22 MCG/0.5 ML - SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - CARTUCCIA (VETRO) - 1.5 ML (12 MILIONI UI/ML) 4 CARTUCCE
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK SERONO EUROPE LIMITED
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	Interferon beta-1a
D.3.2	Product code	[IFNb]
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	interferone beta-1a
D.3.9.1	CAS number	145258-61-3
D.3.9.2	Current sponsor code	IFNb
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	66
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

SARS-CoV 2 infection characterized by a National Early Warning Score lower or equal to 2 and symptoms present for less than 7 days

Infezione da virus SARS-CoV 2 con sintomatologia presente da meno di 7 giorni e punteggio minore o uguale a 2 nella National Early Warning Score (NEWS)

E.1.1.1

Medical condition in easily understood language

Early SARS-CoV 2 infection characterized by mild COVID-19 symptoms

Stato iniziale di infezione da virus SARS-CoV 2 con sintomi lievi di 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	LLT
E.1.2	Classification code	10053983
E.1.2	Term	Corona virus infection
E.1.2	System Organ Class	100000004862

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	10070255
E.1.2	Term	Coronavirus test positive
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary Objective of the study is to evaluate the reduction in disease progression in patients treated with Interferon Beta versus control group within 28 days.

Valutare la riduzione di progressione di malattia in pazienti trattati con interferone beta rispetto a pazienti di controllo entro 28 giorni

E.2.2

Secondary objectives of the trial

Secondary Objectives of the study are: 1) to assess the reduction in ICU admission in patients treated with IFN versus control group; 2) to assess the reduction in number of deaths in IFN compared to control group; 3) to evaluate the increase in proportion of participants returning to negative SARS-CoV 2 RT-PCR in IFN-treated versus control group at Day 14 and Day 28; 4) To assess the increase in SARS-CoV 2-Specific Antibody Titers in IFN-treated compared to control group; 5) to assess the safety of IFN-treated patients.

1) Valutare la riduzione nelle ammissioni in terapia intensiva nei pazienti trattati con interferone rispetto al gruppo di controllo; 2) Valutare la riduzione nel numero di decessi nel gruppo trattato con interferone rispetto al gruppo di controllo; 3) Valutare l'incremento della percentuale di pazienti che negativizza per RT-PCR al SARS-CoV 2 nei pazienti trattati con Interferone rispetto al gruppo di controllo ai giorni 24 e 48; 4) Valutare l'incremento nel titolo di anticorpi specifici per il SARS-CoV 2 nei pazienti trattati con Interferone rispetto al gruppo di controllo; 5) Valutare la sicurezza del trattamento con Interferone

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•>= 65 years of age at time of enrolment;
•Laboratory-confirmed SARS-CoV 2 infection as determined by PCR, in any specimen < 72 hours prior to randomization
•Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures;
•Understands and agrees to comply with planned study procedures;
•Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol
•Being symptomatic for less than 7 days before starting therapy;
•NEWS score =2

Età maggiore di 65 anni;
Infezione da SARS-CoV2 determinata tramite PCR da meno di 72 ore;
Consenso scritto a partecipare allo studio;
Comprensione delle procedure previste dallo studio;
Sintomatologia da meno di 7 giorni prima dell'inizio della terapia;
Punteggio NEWS inferiore o uguale a 2

E.4

Principal exclusion criteria

•Hospitalized patients with illness of any duration, and at least one of the following:
-Clinical assessment (evidence of rales/crackles on exam) AND SpO2 = 94% on room air at rest or after walking test,
OR
-Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen.
•Patients currently using interferon-beta (e.g., multiple sclerosis patients);
•Patients treated with chemotherapy and/or immunosuppressive agents;
•Patients with chronic kidney diseases
•Known allergy or hypersensitivity to interferon (including asthma);
•Any autoimmune disease (resulting from patient anamnesis)
•Patients with signs of dementia or neurocognitive disorders
•Patients with current severe depression and/or suicidal ideations
•Being concurrently involved in another trial
•HIV infection (based on the anamnesis)
•Use of any antiretroviral medication
•Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min);
•Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition);
•Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance;
•Lack or withdrawal of informed consent

•Pazienti ospedalizzati indipendentemente dalla durata della malattia a almeno uno dei seguenti elementi:
-Valutazione clinica (evidenza di rantoli /crepitii) E SpO2 = 94% in aria ambiente,
OPPURE
-insufficienza respiratoria grave (necessità di ventilazione assistita e/o ventilazione con ossigeno).
•Pazienti già in trattamento con interferone-beta (es. pazienti affetti da sclerosi multipla);
•Pazienti in corso di terapia chemioterapica e/o immunosoppressiva;
•Pazienti con patologie renali croniche;
•Allergia o ipersensibilità accertata all’interferone (inclusa asma);
•Qualsiasi patologia autoimmune;
•Pazienti con segni di demenza o disturbi neurocognitivi;
•Pazienti arruolati in altri trial clinici;
•Infezione da HIV (risultante dall’anamnesi);
•Uso di farmaci antivirali;
•Insufficienza renale (GFR (velocità di filtrazione glomerulare) stimata utilizzando la formula EPI-CKD < 30 ml/min);
•Presenza di altre gravi patologie con un impatto sull’aspettativa di vita (es. pazienti che potrebbero non sopravvivere 28 giorni a causa della loro condizione clinica preesistente);
•Presenza di stati depressivi e/o manie suicide;
•Qualsiasi elemento fisico o psicologico che possa indurre lo sperimentatore a ritenere il paziente non idoneo; •
•Assenza del consenso informato o rifiuto di firmarlo.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint of the study is the proportion of patients experiencing a disease progression, during at least 5 days, according to the National Early Warning Score (NEWS). The NEWS score is a standardized approach aimed at promptly detecting signs of clinical deterioration in acutely ill patients and establishing the potential need for higher level of care. It is based on the evaluation of vital signs including respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response. The resulting observations, compared to a normal range, are combined in a single composite “alarm” score. Any other clinical sign clearly indicating a disease worsening will be considered as disease progression.

Riduzione significativa della proporzione di pazienti che va incontro a progressione della malattia in riferimento al punteggio della scala NEWS per almeno 5 giorni nel braccio trattato con IFN-beta rispetto al braccio di controllo.
Il National Early Warning Score (NEWS) è una scala standardizzata creata per identificare tempestivamente segni di deterioramento clinico in pazienti malati e permettere il tempestivo adeguamento della terapia. Si basa sulla valutazione di una serie di parametri vitali come la frequenza degli atti respiratori, la saturazione del sangue, la temperatura, la pressione arteriosa, la frequenza cardiaca, stato di coscienza valutato mediante scala “AVPU”. I parametri rilevati nel paziente malato, confrontati con dei valori di riferimento normali, forniscono un punteggio che caratterizza il livello di “allarme” che bisogna avere per quel paziente. Ogni altro segno clinico che indichi chiaramente un peggioramento della malattia verrà considerato come progressione della malattia.

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days after enrollment

28 giorni dall'arruolamento

E.5.2

Secondary end point(s)

Incidence of adverse events; Change from Baseline in SARS-CoV 2-Specific Binding Antibody Titers at day 28; ICU-free days at 28 days will be calculated as the number of days a patient is not in an ICU; All-cause mortality (Day 1 through Day 28); Negative SARS-CoV 2 RT-PCR at day 14 post-randomization; Negative SARS-CoV 2 RT-PCR at day 28 post-randomization

Incidenza di eventi avversi; Variazione del titolo anticorpale SARS-CoV-2 rispetto al valore basale a 28 giorni; Numero di giorni liberi da terapia intensiva nell’arco temporale di 28 giorni dall’arruolamento; Mortalità a 28 giorni; Negatività al SARS-CoV2 per RT-PCR a 14 giorni; Negatività al SARS-CoV 2 a 28 giorni

E.5.2.1

Timepoint(s) of evaluation of this end point

28 days after randomization; 28 days after randomization; 28 days after randomization; 28 days after randomization; 14 days after randomization; 28 days after randomization

28 giorni dalla randomizzazione; 28 giorni dopo la randomizzazione; 28 giorni dalla randomizzazione; 28 giorni dalla randomizzazione; giorno 14 dalla randomizzazione; 28 giorni dopo la randomizzazione

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

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

Yes

E.8.1.7.1

Other trial design description

stratificazione per sesso

randomization will be stratified by sex

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

Standard di cura

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

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)

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)

Patients will be followed according to NHS and regional standard procedures

I pazienti verranno seguiti secondo le modalità standard previste dal SSN

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

2020-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-06

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

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