Clinical Trials Register

Summary
EudraCT Number:	2020-005557-24
Sponsor's Protocol Code Number:	69HCL18_0996
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-07
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

France - ANSM

A.2

EudraCT number

2020-005557-24

A.3

Full title of the trial

Étude pilote visant à évaluer l’efficacité d’un mélange de kétamine/lidocaïne administré par mésothérapie dans la prise en charge des douleurs neuropathiques du Syndrome Douloureux Régional Complexe de type 1 (SDRC1) - Étude clinique monocentrique randomisée et contrôlée - Étude Méso-SDRC

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Méso-SDRC

A.4.1

Sponsor's protocol code number

69HCL18_0996

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	Hospices Civils de Lyon - Direction de la Recherche Clinique et de l'Innovation
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	Fondation APICIL
B.4.2	Country	France
B.4.1	Name of organisation providing support	Mutuelle MCLR
B.4.2	Country	France
B.4.1	Name of organisation providing support	Medical Innovation
B.4.2	Country	France
B.4.1	Name of organisation providing support	Société Française de Mésothérapie
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	Hospices Civils de Lyon - Direction de la Recherche Clinique et de l'Innovation
B.5.2	Functional name of contact point	Catherine CERESER
B.5.3	Address:
B.5.3.1	Street Address	3 quai des Célestins
B.5.3.2	Town/ city	Lyon cedex 02
B.5.3.3	Post code	69229
B.5.3.4	Country	France
B.5.4	Telephone number	472 40 68 93+33
B.5.5	Fax number	472 11 51 90+33
B.5.6	E-mail	drci_promo@chu-lyon.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Solution stérile apyrogène de lidocaïne chlorhydrate 20 mg
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	Intradermal use Intraepidermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIDOCAINE
D.3.9.1	CAS number	6108-05-0
D.3.9.3	Other descriptive name	LIDOCAINE HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB02922MIG
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	3.33
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	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	Solution stérile apyrogène de lidocaïne chlorhydrate 20 mg et de kétamine 20 mg
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	Intradermal use Intraepidermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIDOCAINE
D.3.9.1	CAS number	6108-05-0
D.3.9.3	Other descriptive name	LIDOCAINE HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB02922MIG
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	3.33
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	KETAMINE
D.3.9.3	Other descriptive name	KETAMINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02830MIG
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	3.33
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: 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	Solution stérile apyrogène de lidocaïne chlorhydrate 20 mg et de kétamine 40 mg
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	Intradermal use Intraepidermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIDOCAINE
D.3.9.1	CAS number	6108-05-0
D.3.9.3	Other descriptive name	LIDOCAINE HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB02922MIG
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	3.33
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	KETAMINE
D.3.9.3	Other descriptive name	KETAMINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02830MIG
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	6.67
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

Complex regional pain syndrome type I

Syndrome Douloureux Régional Complexe de type 1

E.1.1.1

Medical condition in easily understood language

Complex regional pain syndrome type I

Syndrome Douloureux Régional Complexe de type 1

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10064334
E.1.2	Term	Complex regional pain syndrome Type I
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluer l’efficacité d’une association kétamine/lidocaïne comparativement à la lidocaïne seule, administrée par mésothérapie dans la prise en charge des douleurs neuropathiques survenant lors d’un SDRC1, sur l’intensité de la douleur aigüe ou chronique mesurée à l’aide d’une échelle EVA.

E.2.2

Secondary objectives of the trial

Comparer entre les 3 groupes :
1. L’évolution du score EVA ;
2. L’évolution des douleurs neuropathiques ;
3. L’évolution des principales dimensions de la douleur (l’intensité, l’incapacité fonctionnelle, les répercussions sociales et familiales, niveau de détresse psychologique) ;
4. La survenue d’effets indésirables (EI) pertinents du traitement, ainsi que la moyenne des grades les plus élevés des EI pertinents ;
5. La consommation concomitante d’autres antalgiques ;
6. L’évolution de la qualité de vie ;
7. L’EVA et les grades d’EI (balance bénéfice / risque).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Homme/femme d’âge ≥ 18 ans,
- Patient souffrant d’un SDRC1, selon les critères de Budapest, avec une composante neuropathique diagnostiquée par le questionnaire DN4, limitée aux membres inférieurs,
- Patient ayant bénéficié d’une scintigraphie osseuse dynamique trois temps de moins de 6 mois : vasculaire, tissulaire, osseuse, montrant une hypofixation diffuse et extensive au niveau de la zone suspecte de SDRC1,
- Test de grossesse urinaire négatif pour les femmes en âge de procréer,
- EVA > 50 mm (sur une échelle de 0 à 100 mm) à l’inclusion,
- Patient affilié au régime de la sécurité sociale française,
- Patient dont le consentement libre et éclairé a été recueilli par écrit.

E.4

Principal exclusion criteria

- Patient présentant un des antécédents médicaux ou pathologies en cours suivants : épilepsie, HTA (>180mm/ 100mmHg), maladie coronarienne non équilibrée, infarctus du myocarde (IDM) récent (de moins de 12 mois), porphyrie, hyperthyroïdie, maladie de Behçet connue, trouble connu de la crase sanguine ou TP <20%, troubles psychiatriques connus, pathologie ostéoarticulaire septique connue,
- Patient avec infection HIV, immunodépression et/ou traitement immunosuppresseur,
- Insuffisance cardiaque sévère,
- Antécédent d’allergie sévère (œdème de Quincke),
- Allergies connues au Cr et/ou au Ni
- Infection cutanée en cours,
- Patient présentant toute lésion cutanée en regard de la zone d’injection,
- Phobie des injections,
- Hypersensibilité connue au chlorhydrate de kétamine ou au chlorobutanol,
- Hypersensibilité connue au chlorhydrate de lidocaïne ou aux anesthésiques locaux à liaison amide,
- Femme enceinte ou allaitante
- Patient sous mesure de protection (mesure de sauvegarde, curatelle, tutelle) ou privé de liberté.

E.5 End points

E.5.1

Primary end point(s)

Différence de douleur entre l'inclusion et 60 jours, la douleur étant évaluée par une échelle visuelle analogique (EVA 0 - 100 mm).

E.5.1.1

Timepoint(s) of evaluation of this end point

J60

E.5.2

Secondary end point(s)

1. Score EVA (J0, J1, J7, J14, J30, J60)
2. La douleur neuropathique sera évaluée à l’aide de l’auto questionnaire NPSI - Neuropathic Pain Symptom Inventory (J0, J1, J7, J15, J30, J60).
3. Les principales dimensions de la douleur (soit l’intensité, l’incapacité fonctionnelle, les répercussions sociales et familiales ainsi que le niveau de détresse psychologique) seront évaluées à l’aide de l’auto-questionnaire BPI - Brief Pain Inventory (J0, J60).
4. Les effets indésirables (EI) pertinents du traitement, ainsi que la moyenne des grades les plus élevés des EI pertinents, seront recueillis à chacune des visites. (J1, J7, J14, J30, J60). La nature de l’EI et son intensité seront évaluées selon la grille du Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Les EI pertinents, i.e. les EI au moins possiblement reliés au traitement (causalité) seront considérés.
5. La consommation d’autres antalgiques concomitante au traitement sera recueillie. Le médecin interrogera le patient à chaque visite (J0, J7, J14 et J30) ainsi qu’à la dernière visite de suivi concernant la prise d’antalgiques concomitante au traitement.
6. La qualité de vie sera mesurée à l’aide du questionnaire EQ-5D-5L. L’EQ- (J0 et J60) comprenant 5 dimensions : mobilité, autonomie de la personne, activités courantes, douleurs/gênes, anxiété/dépression.
7. Comparer simultanément l’EVA et les grades d’EI pertinents entre les groupes. Cette estimation de la balance bénéfice-risque se fera de façon hiérarchique grâce à la méthode des comparaisons par paires. Elle utilisera l’EVA comme premier critère (bénéfice) et le grade d’EI le plus élevé chez un patient donné comme second critère (risque).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. J0, J1, J7, J14, J30 et J60
2. J0, J1, J7, J15, J30 et J60
3. J0 et J60
4. J1, J7, J14, J30 et J60
5. J0, J7, J14 et J30 et J60
6. J0 et J60
7. J0, J1, J7, J14, J30 et J60

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

Yes

E.8.2.2

Placebo

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

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

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.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

Aucun

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

2021-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-01-12

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