Clinical Trials Register

Summary
EudraCT Number:	2020-001767-86
Sponsor's Protocol Code Number:	COVIRL-002
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-04-15
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

Ireland - HPRA

A.2

EudraCT number

2020-001767-86

A.3

Full title of the trial

An open-label, multi-centre, randomised trial comparing different doses of
single-dose tocilizumab in adults with severe, non-critical, PCR-confirmed COVID-19 infection
with evidence of progressive decline in respiratory function and evolving systemic inflammation
on time to intubation, non-invasive ventilation and/or all-cause mortality

A.3.1

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

trial comparing different doses of single-dose tocilizumab in adults with severe COVID-19 infection

A.4.1

Sponsor's protocol code number

COVIRL-002

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	University College Dublin
B.1.3.4	Country	Ireland
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	University College Dublin
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University College Dublin
B.5.2	Functional name of contact point	QRAM
B.5.3	Address:
B.5.3.1	Street Address	Belfield
B.5.3.2	Town/ city	Dublin
B.5.3.3	Post code	Dublin 4
B.5.3.4	Country	Ireland
B.5.6	E-mail	crc.monitoring@ucd.ie

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	RoActemra
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	Tocilizumab
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	TOCILIZUMAB
D.3.9.1	CAS number	375823-41-9
D.3.9.3	Other descriptive name	TOCILIZUMAB
D.3.9.4	EV Substance Code	SUB20313
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	8
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

E.1.1.1

Medical condition in easily understood language

Coronavirus infection

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 determine the safety and efficacy of standard dose versus low
dose tocilizumab in adults with severe, non-critical, PCR-confirmed
COVID-19 infection with evidence of progressive decline in
respiratory function and evolving systemic inflammation on time to
intubation, non-invasive ventilation and/or all-cause mortality.

E.2.2

Secondary objectives of the trial

In adults with severe, non-critical, PCR-confirmed COVID-19 infection with evidence of progressive decline in respiratory function and evolving systemic inflammation, to determine if single dose
administration of tocilizumab will:
- be safe, as defined by no difference in all-cause mortality compared to standard of care.
- result in a longer time to intubation and non-invasive ventilation and lower all-cause mortality than
standard of care.
- result in similar time to intubation and noninvasive
ventilation and all-cause mortality than standard of care.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Confirmed SARS-CoV2 infection (as defined by positive PCR)
• Evidence of hyper inflammatory state as evidenced by at least
three of the following:
o Documented temperature >38°C in the past 48 hours
o IL6 >40 pg/ml, or in its absence D-dimer >1.5 μgFEU
/ml.
o Elevated CRP (>100mg/L) and/or a three-fold
increase since presentation
o Elevated ferritin X5 ULN
o Elevated LDH (above the ULN)
o Elevated fibrinogen (above the ULN)
• Pulmonary infiltrates on chest imaging
• Moderate to severe respiratory failure as defined by
PaO2/FiO2≤300mmHg
• Aged 18 years or older

E.4

Principal exclusion criteria

• Primary or secondary immunodeficiency
• Use of significant immunosuppressive therapy in the last 3
months (not including hydroxychloroquine or short course of
corticosteroids (defined as <400mg cumulative dose)
• Active malignancy requiring treatment
• Known active current or history of recurrent bacterial,
mycobacterial, fungal or viral infections including history of
untreated latent TB
• History of diverticulitis or chronic ulcerative GI disease that
might predispose to GI perforation
• Severe allergic reaction to monoclonal antibodies
• Pregnancy or breast feeding
• AST / ALT with values greater than 10 times normal levels or
history of significant liver disease that in the opinion of the
investigator precludes use of an investigational agent
• Neutrophils < 0.5 x109/L
• Platelets < 50x109/L
• Documented, uncontrolled sepsis caused by pathogen(s)
other than COVID-19
• Presence of co-morbidities (including cognitive impairment
and/or frailty) that, in the opinion of the investigator, should
preclude use of an investigational agent
• Current skin or soft tissue infection not controlled by
antibiotics
• Body weight ≤ 30kg

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects at day 8 who have reached a
composite primary endpoint of progression to intubation and
ventilation, non-invasive ventilation or death

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 8

E.5.2

Secondary end point(s)

1. Prevalence of new SAE at day 8
2. Proportion of subjects at day 14 and 28 who have reached a
composite primary endpoint of progression to intubation and
ventilation, non-invasive ventilation or death
3. Day 14 and 28 survival
4. Incidence of intercurrent bacterial sepsis (positive blood
culture) or septic shock (regardless of causative agent)
5. Change from baseline to day 8, 14 and 28 in markers of
inflammation (CRP, ferritin, D-dimer, LDH and IL6)
6. Time to PCR negativity and change from baseline in
quantitative SARS-CoV-2 viral load (measured by CT values)
7. Time to PCR negativity from date of onset of symptoms

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Day 8
2. Day 14 and Day 28
3. Day 14 and Day 28
4. Time of event
5. Day 8, Day 14 and Day 28
6. Time of event
7. Time of event

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

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

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

Stage 1 - Standard of Care, Stage 2 - Different Dose of IMP

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

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

Last subject completed the necessary visit/follow-up as per the protocol.

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

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

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)

Standard of care

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

2020-05-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-11-04

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