Clinical Trials Register

Summary
EudraCT Number:	2018-000039-28
Sponsor's Protocol Code Number:	TG6002.02
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:	2018-02-28
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

2018-000039-28

A.3

Full title of the trial

A Phase I/IIa study of TG6002 (VV TK-RR-FCU1) administered by intravenous (IV) infusions in combination with oral flucytosine (5-FC) in patients with advanced gastro-intestinal (GI) tumors

Etude de Phase I/IIa évaluant TG6002 (VV TK-RR-FCU1) administré par perfusion intra-veineuse (IV) en association avec la flucytosine (5-FC) par voie orale chez des patients atteints de tumeurs gastro-intestinales (GI) avancées

A.3.1

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

A clinical study of TG6002 and flucytosine in patients with gastro-intestinal tumors

A.3.2

Name or abbreviated title of the trial where available

TG6002.02

A.4.1

Sponsor's protocol code number

TG6002.02

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	TRANSGENE S.A.
B.1.3.4	Country	France
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	TRANSGENE S.A.
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	TRANSGENE S.A.
B.5.2	Functional name of contact point	Medical Affairs
B.5.3	Address:
B.5.3.1	Street Address	400 boulevard Gonthier d'Andernach, Parc d'Innovation, CS80166
B.5.3.2	Town/ city	Illkirch Graffenstaden cedex
B.5.3.3	Post code	67405
B.5.3.4	Country	France
B.5.4	Telephone number	33388279155
B.5.5	Fax number	33388279141
B.5.6	E-mail	clinical.trials@transgene.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	VV TK-RR-FCU1
D.3.2	Product code	TG6002
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet available
D.3.9.3	Other descriptive name	TG6002 VIRAL PARTICLES
D.3.9.4	EV Substance Code	SUB191372
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	Ancotil
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDA PHARMA
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.3.4	Pharmaceutical form	Tablet
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	FLUCYTOSINE
D.3.9.1	CAS number	2022-85-7
D.3.9.2	Current sponsor code	5-FC
D.3.9.3	Other descriptive name	Ancotil
D.3.9.4	EV Substance Code	SUB07676MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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.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

Gastro-intestinal cancer

Cancer gastro-intestinal

E.1.1.1

Medical condition in easily understood language

Gastro-intestinal cancer

Cancer gastro-intestinal

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10053548
E.1.2	Term	Gastrointestinal cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I: determination of the recommended phase II dose
Phase IIa: efficacy of multiple administrations of TG6002 in combination with flucytosine (or Ancotil or 5-FC)

E.2.2

Secondary objectives of the trial

Phase I: safety and tolerability, efficacy according to RECIST 1.1, TG6002 blood pharmacokinetics, 5-FC, 5-FU and FBAL blood concentrations, detection of neutralizing anti-vaccinia virus antibodies, TG6002 viral shedding in saliva, urine and feces.
Phase IIa: safety, evolution of various tumor marker blood levels over time, TG6002 blood pharmacokinetics, 5-FC, 5-FU and FBAL blood concentrations, detection of neutralizing anti-vaccinia virus antibodies, biodistribution of TG6002 and 5-FC, 5-FU and FBAL concentration in liver metastasis biopsies (in a subgroup of patients with colon cancer and biopsiable liver metastases) and assessment of potential predictive or prognostic biomarkers.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patient population for phase I: patients with advanced GI carcinomas having failed and/or intolerant to standard therapeutic options.
- Patient population for phase IIa: patients with colon cancer and liver metastases having failed and/or intolerant to standard therapeutic options.
- Patient presenting with at least one measurable lesion according to RECIST 1.1 in Phase IIa part of the study (optional in the Phase I part)
- ECOG performance status 0 or 1

E.4

Principal exclusion criteria

- Previous irradiation of target tumor
- MSI-High/dMMR colon cancer patients
- Glomerular filtration rate <60 mL/min/1.73m2 according to the Modification of Diet in Renal Diseases (MDRD) formula
- Immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or immunosuppressant agent, including systemic corticosteroids at a dose >20 mg/day of equivalent prednisolone taken for more than 4 weeks within 3 months prior to TG6002 treatment initiation
- History of severe exfoliative skin condition (e.g. eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to TG6002 treatment initiation

E.5 End points

E.5.1

Primary end point(s)

Phase I: adverse events, serious adverse events, change in standard laboratory parameters and vital signs, dose-limiting toxicities.
Phase IIa: overall response rate.

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase I: days 1, 2, 7 or 8, 14 or 15, 16, 29, 57, 85 and then every 8 weeks.
Phase IIa: days 43 and 85 and then every 8 weeks.

E.5.2

Secondary end point(s)

Phase I:
1) overall response rate
Phase IIa:
1) adverse events, serious adverse events, change in standard laboratory parameters and vital signs, dose-limiting toxicities
Phase I and phase IIa:
2) concentration of TG6002 in blood
3) concentration of 5-FC, 5-FU and FBAL in blood
4) detection of neutralizing anti-vaccinia virus antibodies in blood
5) TG6002 DNA in saliva, urine and feces.

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase I:
1) days 43 and 85 and then every 8 weeks
Phase IIa:
1) days 1, 2, 7 or 8, 14 or 15, 16, 29, 57, 85 and then every 8 weeks
Phase I and phase IIa:
2) days 1, 2, 5, 15, 16, 19 and 28
3) days -1, 5, 7, 14, 19 and 28
4) days -1, 28, 43 and 85
5) days 2 and 7.

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Safety

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

E.8.1.1

Randomised

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

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

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

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

United States

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 visit of the last subject

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

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)

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

2018-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-06-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-02-23

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