Clinical Trials Register

Summary
EudraCT Number:	2020-001408-41
Sponsor's Protocol Code Number:	UKF-MIT-2020-01
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-04-07
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

Germany - PEI

A.2

EudraCT number

2020-001408-41

A.3

Full title of the trial

A prospective, randomized, double blinded placebo-controlled trial to evaluate the efficacy and safety of tocilizumab in patients with severe COVID-19 pneumonia

A.3.1

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

Evaluation of efficacy and safety of an tocilizumab treatment in patients with severe COVID-19 pneumonia

A.3.2

Name or abbreviated title of the trial where available

TOC-COVID

A.4.1

Sponsor's protocol code number

UKF-MIT-2020-01

A.5.4

Other Identifiers

Name:

DRKS

Number:

DRKS00021238

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	Universitätsklinikum Freiburg
B.1.3.4	Country	Germany
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	Universitätsklinikum Freiburg
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Freiburg
B.5.2	Functional name of contact point	Coordinating Investigator
B.5.3	Address:
B.5.3.1	Street Address	Breisacher Straße 153
B.5.3.2	Town/ city	Freiburg i. Br
B.5.3.3	Post code	79110
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4976127034010
B.5.5	Fax number	+497612709633322
B.5.6	E-mail	tobias.wengenmayer@uniklinik-freiburg.de

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	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	Roactemra®
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracavernous use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Roactemra®
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/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe COVID-19 pneumonia

E.1.1.1

Medical condition in easily understood language

In many patients SARS-CoV2 causes a disease named COVID-19. In this trial patients with a pneumonia and severe respiratory insufficiency will be analyzed.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061229
E.1.2	Term	Lung 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

Evaluation of the efficacy and safety of a treatment with Tocilizumab in patients with severe COVID-19 pneumonia

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Proof of SARS-CoV2
2. Severe respiratory failure:
a. ambient air SpO2 ≤ 92% or
b. Need of ≥ 6l O2/min or
c. NIV (non-invasive ventilation) or
d. IMV (invasive mechanical ventilation)
3. ≥ 18 years
4. Written informed consent obtained from the patient or legal authorized representative or investigator consilium (“Gießener Modell”) according to international guidelines and local laws;

E.4

Principal exclusion criteria

1. Non-invasive or invasive mechanical ventilation ≥ 48 hours
2. Pregnancy or breast feeding
3. Liver injury or failure (AST/ALT ≥ 5x ULN)
4. Leukocytes < 2 × 103/µl
5. Thrombocytes < 50 × 103/μl
6. Severe bacterial infection (PCT > 3ng/ml)
7. Acute or chronic diverticulitis
8. Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine)
9. Known active or chronic tuberculosis
10. Known active or chronic viral hepatitis
11. Known allergic reactions to tocilizumab or its ingredients
12. Life expectation of less than 1 year (independent of COVID-19)
13. Participation in any other interventional clinical trial within the last 30 days before the start of this trial
14. Simultaneous participation in other interventional trials (except for participation in COVID 19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
15. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception;
Women can only take part in this study if the risk of becoming pregnant is absolutely minimized. Save contraceptive methods comprise: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception and have to be used while participating in the study

E.5 End points

E.5.1

Primary end point(s)

• Ventilator free days (d) (VFD) in the first 28 days after randomisation
o NIV, IMV and ECMO are defined as ventilator days
o VFD=0, if the patient dies in the first 28 days after randomisation

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days after randomisation

E.5.2

Secondary end point(s)

• Mortality
o 28-day mortality (%)
o Hospital mortality in the first 28 days (%)
• Admission to intensive care unit (ICU) (%)
• Days on ICU in the first 28 days (d)
• IMV free days (d) in the first 28 days after randomisation
o IMV and ECMO are defined as ventilator days
o IMV free days =0, if the patient dies in the first 28 days
• Time to successful extubation within 28 days after randomisation (d)
• Renal failure (%) and renal replacement therapy (%)
• Change of ventilation mode and invasiveness:
o Horowitz Index (paO2/fiO2)
o fiO2 on NIV/IMV
o O2-level on O2 nasal cannula, O2 mask and High-flow nasal cannula
o PEEP und compliance on NIV/IMV
o Extracorporeal membrane oxygenation (ECMO) support
• SOFA-Score
• APACHE-II Score
• Seven-category scale
• Richmond Agitation Sedation Scale (RASS)
• Glasgow Coma Scale
• Laboratory (PCT, IL-6, Ferritin, D-Dimers)

Until end of the study (extended follow up)
• Overall survival after 12 months
• QOL after 6 and 12 months

• Secondary infections/ complications
o Bacterial infection
o Septic shock
o Hepatitis / acute liver injury
o Acute liver failure
o Myocarditis and concomitant cardiogenic shock
o Renal failure
• (Serious) adverse events
• Laboratory parameters
Until end of the study (extended follow up):
• SAEs related to IMP as per investigator’s judgment

E.5.2.1

Timepoint(s) of evaluation of this end point

In the first 28 days after randomisation

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

LPLV

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

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Most subjects will be able to give informed consent. In subjects that are not able to do so - because of sedation in case of mechanical ventilation) - the conservator in law will give the informed consent.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

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)

None.

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

2020-04-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-08-31

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