Clinical Trials Register

Summary
EudraCT Number:	2020-001373-70
Sponsor's Protocol Code Number:	ET20-076
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-03-29
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

France - ANSM

A.2

EudraCT number

2020-001373-70

A.3

Full title of the trial

IMMUNONCOVID-20 : A prospective, controlled, randomized, multicenter study to compare the efficacy of a chloroquine analog (GNS561), anti PD-1 (nivolumab) and anti-interleukine-6 receptor (tocilizumab) versus standard of care in advanced or metastatic cancer patients with SARS-CoV-2 (COVID-19) infection

IMMUNONCOVID-20 - Etude prospective, contrôlée, randomisée, multicentrique comparant l’efficacité d’un analogue de la chloroquine (GNS561), d’une immunothérapie par anti-PD1 (nivolumab) et d’un anti-interleukine-6R (tocilizumab) par rapport à la prise en charge standard chez des patients atteints de cancer avancé ou métastatique et présentant une infection au SARS-CoV-2 (COVID-19)

A.3.1

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

Study comparing the efficacy of a chloroquine analog (GNS561), anti PD-1 (nivolumab) and anti-interleukine-6 receptor (tocilizumab) versus standard of care in advanced or metastatic cancer patients with SARS-CoV-2 (COVID-19) infection

Etude comparant l’efficacité d’un analogue de la chloroquine (GNS561), d’une l’immunothérapie par anti-PD1 (nivolumab) et de l’anti-interleukine-6R (tocilizumab) par rapport à la prise en charge standard chez des patients atteints de cancer avancé ou métastatique et présentant une infection au SARS-CoV-2 (COVID-19)

A.3.2

Name or abbreviated title of the trial where available

IMMUNONCOVID-20

A.4.1

Sponsor's protocol code number

ET20-076

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	Centre Léon Bérard
B.1.3.4	Country	France
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	Genoscience Pharma
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Centre Léon Bérard
B.5.2	Functional name of contact point	Julien GAUTIER
B.5.3	Address:
B.5.3.1	Street Address	28 rue Laennec
B.5.3.2	Town/ city	LYON
B.5.3.3	Post code	69373
B.5.3.4	Country	France
B.5.4	Telephone number	+33426 55 68 29
B.5.5	Fax number	+33478 78 27 15
B.5.6	E-mail	julien.gautier@lyon.unicancer.fr

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.2.5	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	GNS561
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	1914148-72-3
D.3.9.2	Current sponsor code	GNS561
D.3.9.4	EV Substance Code	SUB192575
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 - 200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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.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	Opdivo
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Nivolumab
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	NIVOLUMAB
D.3.9.1	CAS number	NIVOLUMAB
D.3.9.2	Current sponsor code	ET17-093
D.3.9.3	Other descriptive name	NIVOLUMAB
D.3.9.4	EV Substance Code	SUB122750
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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)	Yes
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.IMP: 3
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.2.5	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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

Patients with advanced or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit

Patients présentant un cancer avancé ou métastatique atteint d’une infection par le Sars-CoV-2 et non éligible par une prise en charge en réanimation

E.1.1.1

Medical condition in easily understood language

Patients with advanced or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit

Patients présentant un cancer avancé ou métastatique atteint d’une infection par le Sars-CoV-2 et non éligible par une prise en charge en réanimation

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 main objective is to compare versus standard of care short-term mortality rates in advanced or metastatic cancer patients who are positive for COVID-19 treated with a chloroquine analog (GNS561), an anti-PD1 (nivolumab) or an anti-IL-6R antibody (tocilizumab).

L'objectif principal est de comparer versus le traitement standard les taux de mortalité à court terme chez les patients atteints de cancers avancés ou métastatiques diagnostiqués positifs au COVID-19 traités avec un analogue de la chloroquine (GNS561), une immunothérapie (anti-PD1) ou un anticorps anti-IL-6R (tocilizumab).

E.2.2

Secondary objectives of the trial

The secondary objectives will be to describe in each arm of the study:
• Time to clinical improvement
• Clinical status at days 7, 14 and 28
• Mean change in clinical status from baseline to days 7, 14 and 28
• Overall survival
• Length of stay in Intensive Care Unit and in Resuscitation Unit
• Duration of mechanical ventilation or high flow oxygen devices
• Duration of hospitalization
• Rate of throat swab negativation at days 7, 14 and 28
• Quantitative SARS-CoV-2 virus in throat swab at days 7, 14 and 28
• Quantitative SARS-CoV-2 virus in blood at days 7, 14 and 28
• Rate of secondary infection by other documented pathogens (bacteria, fungi)
• Biological parameters (hematological parameters and markers of inflammation)
• Safety of experimental treatments.
And to perform Cost-Effectiveness Analyses (CEA) with Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.

Les objectifs secondaires seront de décrire dans chaque bras de l'étude :
• Temps à amélioration clinique
• État clinique à J7, 14 et 28
• Changement moyen de l’état clinique entre baseline et J7, 14 et 28
• La survie globale
• Durée du séjour en unité de soins intensifs et en unité de réanimation
• Durée de la ventilation mécanique ou des dispositifs d’oxygène à haut débit
• Durée d'hospitalisation
• Taux de négativation de l'écouvillonnage pharyngé à J7, 14 et 28
• Mesure quantitative du SRAS-CoV-2 dans un écouvillonnage pharyngé à J7, 14 et 28
• Mesure quantitative du SRAS-CoV-2 dans le sang à J7, 14 et 28
• Taux d'infection secondaire par d'autres agents pathogènes documentés (bactéries, champignons)
• Paramètres biologiques (paramètres hématologiques et marqueurs de l'inflammation)
• Tolérance des traitements expérimentaux
Et de réaliser une analyses coût-efficacité avec ratio coût-efficacité incrémental exprimé en coût par année de vie gagnée.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

I1. Age 18 or older at the time of enrolment.
I2. Histologically or cytologically confirmed diagnosis of advanced or metastatic hematological or solid tumor (hematological or solid tumor, any type and any localization).
I3. Documented diagnosis of COVID-19 (diagnostic test performed in a certified laboratory) or symptoms of COVID-19 associated with radiological signs of pneumonia as described by Shi et al.;
I4. Cohort 2: patients with pneumonia confirmed by chest imaging, and an oxygen saturation (Sao2) of 94% or less while they are breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (Pao2:Fio2) at or below 300 mg Hg.
...See the protocol

I1. Age > 18 ans à la date de signature du consentement éclairé de participation
I2. Diagnostic confirmé histologiquement de cancer solide ou hématologique, en situation avancée ou métastatique (quel que soit le type et la localisation)
I3. Diagnostic de COVID-19 documenté (test de dépistage réalisé par un laboratoire certifié) ou symptômes de COVID-19 associés à des signes radiologiques de pneumonie tels que décrits par Shi et al. ;
I4. Cohorte 2 : Patient présentant une pneumonie confirmée par une imagerie thoracique et une saturation en oxygène (Sao2) de 94% ou moins lorsqu’il respire l’air ambiant ou un rapport de la pression partielle d’oxygène (Pao2) à la fraction d’oxygène inspiré (Fio2) (Pao2:Fio2) égal ou inférieur à 300 mmHg.
...Voir le protocole

E.4

Principal exclusion criteria

E1. For cohort 1 only : Patient currently receiving therapy with an anti- PD-1, anti- PD-L1, or anti-CTLA4.
E2. For cohort 2 only: Patient currently receiving therapy with an anti- IL-6 or anti-IL-6R.
E3. Contraindication to treatment with nivolumab (cohort 1 only) or to tocilizumab (cohort 2 only) as per respective SPC, including known hypersensitivity to one of these study drugs or severe hypersensitivity reaction to any monoclonal antibody.
E4. Patient known to have intolerance or hypersensitivity to chloroquine or any quinoline derivates (e.g., quinine, chloroquine, mefloquine).
...See the protocol

E1. Pour la cohorte 1 uniquement : patient recevant actuellement un traitement avec un anti-PD-1, anti-PD-L1 ou anti-CTLA4.
E2. Pour la cohorte 2 uniquement : Patient recevant actuellement un traitement avec un anti-IL-6 ou anti-IL-6R.
E3. Contre-indication au traitement par nivolumab (cohorte 1 uniquement) ou par tocilizumab (cohorte 2 uniquement) selon les RCP respectifs, y compris l'hypersensibilité connue à l'un de ces médicaments à l'étude ou une réaction d'hypersensibilité sévère à tout anticorps monoclonal.
E4. Patient connu pour présenter une intolérance ou une hypersensibilité à la chloroquine ou à tout dérivé de la quinoline (par exemple, quinine, chloroquine, méfloquine).
...Voir le protocole

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the 28-day survival rate, defined by the proportion of patients still alive 28 days after randomization.

Le critère de jugement principal sera le taux de survie à 28 jours, défini par la proportion de patients en vie 28 jours après la randomisation.

E.5.1.1

Timepoint(s) of evaluation of this end point

28-day

28 jours

E.5.2

Secondary end point(s)

• Time to clinical improvement
• Clinical status at D7, D14 and D28 • Mean change in clinical status from baseline to days 7, 14 and 28
• Overall survival
...See the protocol

• Temps nécessaire à l'amélioration clinique
• État clinique à J7, J14 et J28
• Changement moyen de l'état clinique de la ligne de base aux jours 7, 14 et 28
• La survie globale
... Voir le protocole

E.5.2.1

Timepoint(s) of evaluation of this end point

Assessment at a beginning and throughout the study

Evaluation au début et ce tout au long de l'étude

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

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

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Information not present in EudraCT

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)

Information not present in EudraCT

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

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

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

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

Dernière visite du dernier patient

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:

147

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

126

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

273

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)

Investigator’s discretion

A la discrétion du médecin

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

2020-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-01

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-07-06

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