Clinical Trials Register

Summary
EudraCT Number:	2020-001497-30
Sponsor's Protocol Code Number:	ALXN1210-COV-305
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:	2021-01-12
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

2020-001497-30

A.3

Full title of the trial

A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

Studio di Fase 3, in aperto, randomizzato, controllato, per valutare l’efficacia e la sicurezza di ravulizumab somministrato per via endovenosa rispetto alla migliore terapia di supporto in pazienti con polmonite grave, lesione polmonare acuta o sindrome da distress respiratorio acuto da COVID-19

A.3.1

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

ravulizumab for the treatment of patients with Coronavirus Disease 2019

ravulizumab per il trattamento dei pazienti con malattia da Coronavirus 2019

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

ALXN1210-COV-305

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04369469

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	ALEXION PHARMACEUTICALS INCORPORATED
B.1.3.4	Country	United States
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	Alexion Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alexion Europe SAS
B.5.2	Functional name of contact point	European Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	103–105 rue Anatole France
B.5.3.2	Town/ city	Levallois-Perret
B.5.3.3	Post code	92300
B.5.3.4	Country	France
B.5.4	Telephone number	0033147100615
B.5.5	Fax number	0033147100611
B.5.6	E-mail	clinicaltrials.eu@alexion.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	No
D.2.1.1.1	Trade name	Ultomiris
D.2.1.1.2	Name of the Marketing Authorisation holder	Alexion Europe SAS - EU/1/19/1371/001
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	ravulizumab
D.3.2	Product code	[ALXN1210]
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	ravulizumab
D.3.9.2	Current sponsor code	ALXN1210
D.3.9.4	EV Substance Code	SUB172162
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	10
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

COVID-19 severe pneumonia, acute lung injury, or acute respiratory distress syndrome

Polmonite grave, lesione polmonare acuta o sindrome da distress respiratorio acuto da COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19 pneumonia

Polmonite 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	10061229
E.1.2	Term	Lung infection
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 effect of ravulizumab + Best Supportive Care (BSC) compared with BSC alone on the survival of patients with COVID-19

Valutare l’effetto di ravulizumab + migliore terapia di supporto (best supportive care, BSC) rispetto alla BSC da sola sulla sopravvivenza dei pazienti con COVID-19

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of ravulizumab + BSC compared with BSC alone on outcomes in patients with COVID-19
To characterize the overall safety of ravulizumab + BSC compared with BSC alone in patients with COVID-19
To characterize the PK/PD and immunogenicity of ravulizumab in patients with COVID-19
To assess the effect of C5 inhibition on systemic activation of complement and inflammation in patients with COVID-19

Valutare l’efficacia di ravulizumab + BSC rispetto alla BSC da sola sugli esiti nei pazienti con COVID-19
Caratterizzare la sicurezza complessiva di ravulizumab + BSC rispetto alla BSC da sola nei pazienti con COVID-19
Caratterizzare PK/PD e immunogenicità di ravulizumab nei pazienti con COVID-19
Valutare l’effetto dell’inibizione di C5 sull’attivazione sistemica del complemento e sull’infiammazione nei pazienti con COVID-19

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females = 18 years of age and = 40 kg at the time of providing informed consent.
2. Confirmed diagnosis of SARS-CoV-2 infection presenting as severe COVID-19 requiring hospitalization.
3. Severe pneumonia, acute lung injury, or ARDS confirmed by computed tomography (CT) or X-ray at Screening or within the 3 days prior to Screening, as part of the patient's routine clinical care.
4. Respiratory Distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or noninvasive (with continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]).
5. Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified contraception guidance for avoiding pregnancy for 8 months after treatment with the study drug.

1. Soggetti di sesso maschile o femminile di età =18 anni e con peso =40 kg al momento della firma del consenso informato.
2. Diagnosi confermata di infezione da SARS-CoV-2 che si presenta come COVID-19 grave che richiede il ricovero in ospedale.
3. Polmonite grave, lesione polmonare acuta o sindrome da distress respiratorio acuto (ARDS) confermate da tomografia computerizzata (TAC) o radiografia allo screening o entro i 3 giorni precedenti lo screening, come parte delle cure cliniche di routine del paziente.
4. Distress respiratorio che richiede ventilazione meccanica, che può essere invasiva (che richiede intubazione endotracheale) o non invasiva (con pressione positiva continua delle vie aeree [CPAP] o pressione positiva bilivello delle vie aeree [BiPAP]).
5. Le pazienti in età fertile e i pazienti di sesso maschile con compagne di sesso femminile in età fertile devono seguire le linee guida di contraccezione previste dal protocollo per evitare una gravidanza negli 8 mesi successivi al trattamento con il farmaco dello studio.

E.4

Principal exclusion criteria

1. Patient is not expected to survive for more than 24 hours.
2. Patient is on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening.
3. Severe pre-existing cardiac disease (ie, New York Heart Association Class 3 or Class 4, acute coronary syndrome or persistent ventricular tachyarrhythmias).
4. Patient has an unresolved Neisseria meningitidis infection.
5. Use of the following medications and therapies:
a. Current treatment with a complement inhibitor,
b. Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on Day 1.
6.Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half -lives of that investigational therapy, whichever is greater
Exceptions:
a.Investigational therapies will be allowed if received as part of best supportive care through an expanded access protocol or emergency approval for the treatment of COVID 19.
b.Investigational antiviral therapies (such as remdesivir) will be allowed even if received as part of a clinical study.
7. Female patients who are breastfeeding or who have a positive pregnancy test result at Screening.
8. History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
9.Patient who is not currently vaccinated against N. meningitidis, unless the patient agrees to receive prophylactic treatment with appropriate antibiotics for at least 8 months after the last infusion of study drug or until at least 2 weeks after the patient receives vaccination against N. meningitidis.

1. Non si prevede che il paziente sopravviva per più di 24 ore.
2. Il paziente è in ventilazione meccanica invasiva con intubazione per più di 48 ore prima dello screening.
3. Grave malattia cardiaca preesistente (vale a dire, classe 3 o 4 della New York Heart Association o sindrome coronarica acuta o tachicardie ventricolari persistenti).
4. Il paziente ha un’infezione da Neisseria meningitidis non risolta.
5. Uso dei seguenti farmaci e terapie:
a. Attuale trattamento con un inibitore del complemento,
b. Immunoglobulina endovenosa (IVIg) nelle 4 settimane precedentila randomizzazione al giorno 1.
6.Trattamento con terapia sperimentale in uno studio clinico entro 30 giorni prima della randomizzazione, o entro 5 emivite di quella terapia sperimentale, a seconda di quale sia maggiore
Eccezioni:
a. Le terapie investigative saranno consentite se ricevute come parte delle migliori cure di supporto attraverso un protocollo di accesso esteso o l'approvazione di emergenza per il trattamento di COVID 19.
b. Le terapie antivirali sperimentali (come il remdesivir) saranno consentite anche se ricevute come parte di uno studio clinico.
7. Pazienti di sesso femminile che allattano o che hanno un risultato positivo al test di gravidanza allo Screening.
8. Storia di ipersensibilità a qualsiasi ingrediente contenuto nel farmaco in studio, inclusa l'ipersensibilità alle proteine ¿¿murine.
9.Paziente che non è attualmente vaccinato contro N. meningitidis, a meno che il paziente non accetti di ricevere un trattamento profilattico con antibiotici appropriati per almeno 8 mesi dopo l'ultima infusione del farmaco in studio o fino ad almeno 2 settimane dopo che il paziente riceve la vaccinazione contro N. meningitidis.

E.5 End points

E.5.1

Primary end point(s)

Survival

Sopravvivenza

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 29

Al giorno 29

E.5.2

Secondary end point(s)

- Number of days free of mechanical ventilation at day 29
- Duration of intensive care unit stay at day 29
- Change from baseline in SOFA score at day 29
- Change from baseline in SpO2/FiO2 at Day 29
- Duration of hospitalization at day 29
- Survival (based on all-cause mortality) at Day 60 and Day 90

- Numero di giorni senza ventilazione meccanica al giorno 29
- Durata della degenza in terapia intensiva al giorno 29
- Variazione rispetto al basale nel punteggio SOFA al giorno 29
- Variazione rispetto al basale di SpO2 / FiO2 al giorno 29
- Durata del ricovero al giorno 29
- Sopravvivenza (basata sulla mortalità per tutte le cause) al giorno 60 e al giorno 90

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 29
Day 60 and Day 90 (survival only)

Giorno 29
Giorno 60 e Giorno 90 (solo sopravvivenza)

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

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

Immunogenicità

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)

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

Migliore terapia di supporto

Best Supportive 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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Japan

United States

France

Germany

Italy

Spain

United Kingdom

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

Unconscious patients

Pazienti incoscienti

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

geriatric patients

Pazienti geriatrici

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

135

F.4.2.2

In the whole clinical trial

270

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 return to the care of his/her physician

I pazienti torneranno in cura dal proprio medico

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

2020-12-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-21

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

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