Clinical Trials Register

Summary
EudraCT Number:	2020-001167-93
Sponsor's Protocol Code Number:	Sobi.IMMUNO-101
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	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

2020-001167-93

A.3

Full title of the trial

A phase 2/3, randomized, open-label, parallel group, 3-arm, multicenter study investigating the efficacy and safety of intravenous administrations of emapalumab, an anti-interferon gamma (anti-IFN¿) monoclonal antibody, and anakinra, an interleukin-1(IL-1) receptor antagonist, versus standard of care, in reducing hyper-inflammation and respiratory distress
in patients with SARS-CoV-2 infection.

Studio di Fase 2/3, randomizzato, in aperto, a 3 gruppi paralleli, multicentrico per valutare l’efficacia e la sicurezza di somministrazioni endovenose di emapalumab, un anticorpo monoclonale anti-interferone gamma (anti-IFN¿), e di anakinra, un antagonista del recettore per la interleuchina-1(IL-1), a confronto con terapia standard, nel ridurre l’iper-infiammazione e il distress respiratorio in pazienti con infezione da SARS-CoV-2

A.3.1

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

A clinical trial investigating efficacy and safety of emapalumab and anakinra in patients with Coronavirus disease (COVID-19)

Studio clinico per valutare l'efficacia e la sicurezza di emapalumab e anakinra in pazienti con COVID-19

A.3.2

Name or abbreviated title of the trial where available

Sobi.IMMUNO-101

A.4.1

Sponsor's protocol code number

Sobi.IMMUNO-101

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	SWEDISH ORPHAN BIOVITRUM AB (PUBL)
B.1.3.4	Country	Sweden
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	Swedish Orphan Biovitrum AB (publ)
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Swedish Orphan Biovitrum AG
B.5.2	Functional name of contact point	Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Messeplatz 10
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4058
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41412202440
B.5.6	E-mail	mail.ch@sobi.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	KINERET - "100 MG/0,67 ML SOLUZIONE INIETTABILE" USO SOTTOCUTANEO SIRINGA PRERIEMPITA 7 SIRINGHE PRERIEMPITE
D.2.1.1.2	Name of the Marketing Authorisation holder	SWEDISH ORPHAN BIOVITRUM AB (PUBL)
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	Kineret
D.3.2	Product code	[Kineret]
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ANAKINRA
D.3.9.1	CAS number	143090-92-0
D.3.9.2	Current sponsor code	Anakinra
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	150
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.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	Gamifant
D.2.1.1.2	Name of the Marketing Authorisation holder	Swedish Orphan Biovitrum AB (publ)
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Emapalumab
D.3.2	Product code	[Emapalumab]
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Emapalumab
D.3.9.1	CAS number	1709815-23-5
D.3.9.2	Current sponsor code	Emapalumab
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	5
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

SARS-CoV-2 infection

Infezione da SARS-CoV-2

E.1.1.1

Medical condition in easily understood language

Coronavirus disease (COVID-19)

Malattia da Coronavirus (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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10021881
E.1.2	Term	Infections and infestations
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

The primary objective of this study is to assess the effect of emapalumab and anakinra on hyperinflammation and pulmonary function in patients with SARS-CoV-2 infection.

L’obiettivo principale di questo studio è la valutazione degli effetti di emapalumab e anakinra sulla iper-inflammazione e la funzione polmonare in pazienti con infezione da SARS-CoV-2.

E.2.2

Secondary objectives of the trial

The secondary objective of this study is to evaluate the safety and tolerability profile of intravenous (i.v.) administrations of emapalumab and anakinra in patients with SARS-CoV-2 infection.

L’obiettivo secondario di questo studio è la valutazione della sicurezza e della tollerabilità di somministrazioni endovenose di emapalumab e anakinra in pazienzi con infezione da SARS-CoV-2.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent provided by the patient, or by the patient's legally authorized representative(s), as applicable.
2. Documented presence of SARS-CoV-2 infection as per hospital routine.
3. Age > 30 to < 80 years at the time of screening.
4. Presence of respiratory distress, defined as:
a. PaO2/FiO2 < 300 mm Hg and >200 mm Hg or
b. RR =30 breaths/min or
c. SpO2 <93% in air at rest.
Note: Patients given CPAP ventilator support are eligible for inclusion.
5. Presence of hyperinflammation defined as:
a. Lymphocyte counts < 1000 cells/µL, and
b. Two of the following three criteria:
i. Ferritin > 500 ng/mL
ii. LDH > 300 U/L
iii. D-Dimers > 1000 ng/mL

1. Firma del consenso informato da parte del paziente, o del/i tutore/i legale/i, se applicabile.
2. Diagnosi documentata di infezione da SARS-CoV-2, secondo quanto previsto dalla routine ospedaliera.
3. Età > 30 e < 80 anni al momento dello screening.
4. Presenza di difficoltà respiratorie, definite come:
a. Rapporto PaO2/FiO2 < 300 mm Hg e >200 mm Hg oppure
b. Frequenza respiratoria =30 atti respiratori/min oppure
c. Saturazione di O2 <93% in aria ambiente a riposo.
Nota: Pazienti che richiedono supporto con casco CPAP possono essere inclusi nello studio.
5. Presenza di iper-infiammazione definita come:
a. Conta linfocitaria < 1000 cellule/µL, piú
b. Due dei 3 criteri seguenti:
i. Ferritina > 500 ng/mL
ii. LDH > 300 U/L
iii. D-Dimeri > 1000 ng/mL

E.4

Principal exclusion criteria

1. Patients in mechanical ventilation or with MEWS score >4 with evidence of moderate or above ARDS (Berlin definition, namely with PaO2/FiO2 >100, but <200 mm Hg) or severe respiratory insufficiency or evidence of rapid worsening (respiratory distress requiring mechanical ventilation or presence of shock or presence of concomitant
organ failure requiring ICU admission).
2. Impairment of cardiac function defined as poorly controlled heart diseases, such as NYHA class II (mild) and above, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention.
3. Severe renal dysfunction (estimated glomerular filtration rate =30mL/min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
4. Uncontrolled hypertension (seated systolic blood pressure >180mmHg, or diastolic blood pressure >110mmHg) .
5. Administration of plasma from convalescent patients who recovered from SARS-CoV-2 infection.
6. Clinical suspicion of latent tuberculosis.
7. History of hypersensitivity or allergy to any component of the study drug.
8. Pregnant women.
9. Existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion.
10. Enrollment in another concurrent clinical interventional study, or intake of an investigational drug within three months or 5 half-lives prior to inclusion in this study, if considered interfering with this study objectives as assessed by the Investigator.
11. Foreseeable inability to cooperate with given instructions or study procedures.

1. Pazienti in ventilazione assistita o con punteggio MEWS >4 con evidenza di difficoltà respiratorie di grado moderato o piú gravi (secondo le definizioni di Berlino, in particolare rapporto PaO2/FiO2 >100, ma <200 mm Hg) o insufficienza respiratoria severa o evidenza di rapido deterioramento (difficoltà respiratoria che richieda ventilazione assistita o shock o presenza di una insufficienza d’organo concomitante che richieda il trasferimento in Terapia Intensiva).
2. Compromissione della funzionalità cardiaca, definita come insufficienza cardiaca mal controllata, come ad esempio quella di classe II NYHA (lieve) o piú grave, angina instabile, infarto miocardico nei 12 mesi precendenti lo screening, aritmie sopraventricolari e ventricolari che richiedano un trattamento.
3. Insufficienza renale grave (stima della velocità di filtrazione glomerulare = 30mL/min/1.73 m2) o in terapia di sostituzione renale continua, emodialisi, o dialisi peritoneale.
4. Ipertensione non controllata (pressione sistolica > 180mmHg, o diastolica > 110mmHg, da seduto).
5. Somministrazione di plasma di pazienti convalescenti per una infezione da SARS-CoV-2.
6. Sospetto clinico di tubercolosi latente.
7. Reazioni pregresse di ipersensibilità o allergia a componenti dei farmaci in studio.
8. Gravidanza.
9. Presenza di una patologia concomitante che rappresenta un pericolo per la vita o di ogni altra condizione clinica per cui, secondo il parare dello sperimentatore, il paziente non sia eleggibile.
10. Partecipazione ad un altro studio interventistico, o assunzione di altri farmaci sperimentali nei 3 mesi precedenti lo screening (o per meno di 5 emivite), nel caso in cui lo sperimentatore ritenga che ció possa interferire con gli obiettivi dello studio.
11. Impossibilità ad aderire alle procedure dello studio.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is treatment success, defined as not requiring any of the following by Day 15:
• Invasive mechanical ventilation or
• Extracorporeal membrane oxygenation (ECMO).

L’endpoint primario di efficacia è rappresentato dalla percentuale di successo del trattamento, definita come la percentuale di pazienti che, entro il Giorno 15, non necessitano di:
• Ventilazione assistita oppure
• Ossigenazione extracorporea a membrana (ECMO).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 15

Giorno 15

E.5.2

Secondary end point(s)

• Treatment-emergent severe fatal and life-threatening serious adverse events (SAEs).
• Adverse events leading to premature discontinuation of study treatment.
• Anaphylactic/anaphylactoid reactions.
• Treatment emergent adverse events of special interest:
o Emapalumab treatment group: Infections caused by pathogens potentially favored by IFN-gamma neutralizations such as mycobacteria, salmonella, shigella, herpes zoster and histoplasma capsulatum, and severe infusion-related reactions.
o Anakinra treatment group: Severe neutropenia.
• Treatment-emergent laboratory abnormalities.

• Eventi avversi seri (SAEs) durante il trattamento che siano fatali o mettano in pericolo la vita.
• Eventi avversi che causino l’interruzione anticipata del farmaco in studio.
• Reazioni anafilattiche o anafilattoidi.
• Eventi avversi di interesse durante il trattamento:
o Pazienti che ricevono emapalumab: infezioni causate da agenti patogeni potenzialmente favoriti dalla neutralizzazione di IFN-gamma, ad esempio micobatteri, salmonella, shigella, herpes zoster e istoplasma capsulato, e reazioni gravi correlate alla infusione del farmaco.
o Pazienti che ricevono anakinra: neutropenia grave.
• Alterazioni di parametri di laboratorio durante il trattamento.

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety is followed throughout the study

La sicurezza è valutata per tutta la durata dello studio

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)

Yes

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

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

Terapia standard

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

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

The end of this study is defined as the date of the last patient's last visit/end of study call (Visit 8, Week 10).

La conclusione della sperimentazione è definita come LVLS (Visita 8, 10 settimana)

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

if the patient is unconscious as an example, the legal representative can give the consent

se il paziente non è cosciente il consenso deve essere fornito dal legale rappresentante

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)

Not applicable

Non applicabile

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

2020-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-27

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

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