Clinical Trials Register

Summary
EudraCT Number:	2018-001978-22
Sponsor's Protocol Code Number:	I17004
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2018-09-17
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

2018-001978-22

A.3

Full title of the trial

Injections of Sodium Thiosulfate for ectopic calcifications or ossifications. A pilot study.

Injections de thiosulfate de sodium dans le traitement de calcifications ou d’ossifications ectopiques. Etude pilote

A.3.1

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

Injections of Sodium Thiosulfate for ectopic calcifications or ossifications. A pilot study.

Injections intralésionnelles de thiosulfate de sodium dans le traitement de calcifications ou d’ossifications ectopiques. Etude pilote

A.3.2

Name or abbreviated title of the trial where available

ITS Pilot

A.4.1

Sponsor's protocol code number

I17004

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	CHU de LIMOGES
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	DGOS
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	CHU de LIMOGES
B.5.2	Functional name of contact point	Direction Research and Innovation
B.5.3	Address:
B.5.3.1	Street Address	2 avenue Martin Luther King
B.5.3.2	Town/ city	LIMOGES
B.5.3.3	Post code	87042
B.5.3.4	Country	France
B.5.4	Telephone number	+33555056349
B.5.5	Fax number	+33555056696
B.5.6	E-mail	drc@chu-limoges.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	Yes
D.2.1.1.1	Trade name	Sodium Thiosulfate 10%
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Franz Köhler Chemie GmbH
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	Sodium thiosulfate
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium thiosulfate 10%
D.3.9.3	Other descriptive name	SODIUM THIOSULFATE PENTAHYDRATE
D.3.9.4	EV Substance Code	SUB22204
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

Patient presenting with:
- ectopic ossification secondary to iPPSD2 or
- ectopic calcification secondary to dermatomyositis or
- ectopic calcification secondary to systemic sclerosis

E.1.1.1

Medical condition in easily understood language

Patient presenting with:
- ectopic ossification secondary to iPPSD2 or
- ectopic calcification secondary to dermatomyositis or
- ectopic calcification secondary to systemic sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10006935
E.1.2	Term	Calcification and ossification, unspecified
E.1.2	System Organ Class	100000004867

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate, after a run-in period of 6 months, the efficacy of a 6- month treatment of 10% STS solution when locally injected for the treatment of calcifications (secondary to dermatomyositis or systemic sclerosis) and ectopic ossifications (secondary to iPPSD2)

Evaluer, après une phase d’observation de 6 mois, l’efficacité de l’administration locale de TSS 10% pendant 6 mois pour le traitement des calcifications (secondaires à une dermatomyosite ou une sclérodermie systémique) et des ossifications (secondaires à un iPPSD2

E.2.2

Secondary objectives of the trial

To evaluate in each disease (dermatomyositis, systemic sclerosis and iPPSD2):

1) the evolution of ectopic calcification/ossification volume between (i) time of inclusion, (ii) the end of the run-in period (i.e. 6 months after inclusion) and (iii) after 6 months of local injections of STS)

2) the safety of local injections of STS during 6 months of treatment

3) the evolution of the ectopic calcification/ossification density in between (i) time of inclusion, (ii) the end of the run-in period (6 months after inclusion) and (iii) after 6 months of local injections of STS

4) the percentage of clinically pertinent variation of pain after the 6 month run-in period and after the 6 months of local injections of STS

5) the percentage of clinically pertinent variation of quality of life after the 6-month run-in period and after the 6 months of local injections of STS

Evaluer dans chaque groupe de pathologie (dermatomyosite, sclérodermie systémique et iPPSD2) :

1) l’évolution du volume des calcifications/ossifications ectopiques entre (i) l’inclusion (M0), (ii) la fin de la phase d’observation prospective (M6) et (iii) après l’administration locale de TSS (M12)

2) la tolérance de l’administration locale de TSS pendant la durée du traitement (6 mois)

3) l’évolution de la densité des calcifications /ossifications ectopiques entre (i) l’inclusion (M0), (ii) la fin de la phase d’observation prospective (M6) et (iii) après l’administration locale de TSS (M12)

4) le pourcentage de variation cliniquement pertinent de douleur après la phase d’observation prospective et après l’administration locale de TSS

5) le pourcentage de variation cliniquement pertinent de qualité de vie après la phase d’observation prospective et après l’administration locale de TSS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient presenting with:
● ectopic calcification secondary to dermatomyositis or ● ectopic calcification secondary to systemic sclerosis And aged 18 years old or higher
OR
● ectopic ossification secondary to iPPSD2
And aged ≥ 2 years old and ≤ 17 years old
And after the specific authorization of ANSM and CPP
- Indication of STS injection validated by a multidisciplinary committee, based on the significant morbidity and/or functional impact of the targeted calcification/ossification
- Patient with no planned surgery of the calcifications/ossifications for the twelve coming months
-Women of childbearing potential on highly effective contraception (such as hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence). Contraception will be extended up to one month after the last injection.
- Informed consent signed by the patient / parents
- Patient affiliated to (or beneficiary of) the social security system

E.4

Principal exclusion criteria

- Allergy to STS, sulfites or one of the excipients used
- Contraindication to local injection of STS
- Anticoagulant therapy
- Pregnant, parturient or breastfeeding woman
- Patient deprived of freedom by a court judgment or an administrative decision
- Patient undergoing psychiatric care under coercion
- Legally protected adult patients (guardianship / curatorship)
- Patient unable to give consent
- Patient placed under judicial protection

- patient présentant une allergie au TSS, aux sulfites ou à l’un de ses excipients
- patient présentant une contre indication à l’administration locale de TSS
- patient prenant un traitement anticoagulant
- femme enceinte, parturiente ou allaitant
- patient privé de liberté par décision judiciaire ou administrative
- patient faisant l’objet de soins psychiatriques sous la contrainte
- patient majeur faisant l’objet d’une mesure de protection légale (tutelle / curatelle)
- patient majeur hors d’état d’exprimer son consentement
- patient sous mesure de sauvegarde de justice

E.5 End points

E.5.1

Primary end point(s)

Percentage of volume evolution of the treated calcifications / ossifications between the beginning (M6) and the end (M12) of STS treatment, in each of the three diseases (dermatomyositis, systemic sclerosis and iPPSD2), evaluated on CT-scan measurements.

Pourcentage d’évolution du volume des calcifications / ossifications traitées entre le début (M6) et la fin (M12) du traitement par TSS, dans chaque groupe de pathologie (dermatomyosite, sclérodermie systémique et iPPSD2), mesuré par scanner.

E.5.1.1

Timepoint(s) of evaluation of this end point

month 12

12 mois

E.5.2

Secondary end point(s)

1) Volume of the treated calcifications / ossifications at (i) inclusion (M0), the end of the run-in period (M6) and after 6 months of local injections of STS (M12) in each disease, evaluated on CT-scan measurements.

2) (i) Adverse events (clinical and biological): causality, severity, and seriousness (outcome, drug discontinuation or drug reduction due to AE) during the 6 months of STS treatment.(ii) Trabecular bone density calculated through measurements of Hounsfield units level within the bone facing the treated area on M0, M6 and M12 CT evaluations. (iii) pain associated with STS infusion or injections.

3) Hounsfield density of the treated ectopic calcifications/ossifications at (i) inclusion (M0), the end of the run-in period (M6) and after 6 months of local injections of STS (M12), evaluated on CT-scan measurements.

4) Percentage of clinically pertinent variation in pain evaluated with pain scales: difference in HEDEN ≥ 2 (2-7 years old), difference in VAS score ≥ 2 (> 7 years old) between M0-M6 and M6-M12.

5) Percentage of clinically pertinent variation in quality of life evaluated with quality of life scales: difference in PedsQL Scale ≥ 5 (2 years old -18 years old, using appropriates reports), difference in SF36 score ≥ 20 (> 18 years old) between M0-M6 and M6-M12.

1) pourcentage d’évolution du volume des calcifications / ossifications entre (i) l’inclusion (M0), (ii) la fin de la phase d’observation (M6) et (iii) la fin du traitement par TSS (M12), dans chaque pathologie, mesuré par scanner

2) (i) Effets indésirables (cliniques et biologiques) : causalité, sévérité et gravité (critère de jugement, arrêt du traitement ou diminution de la dose en raison d'un EI) pendant les 6 mois du traitement par TSS. (ii) Densité osseuse trabéculaire (unités de Hounsfield) mesurée au niveau de l'os en regard de la zone traitée lors des évaluations par scanner à M0, M6 et M12. (iii) douleur associée à l’administration du TSS (injections sous-cutanées ou par pompe).

3) variation de densité de Hounsfield des calcifications / ossifications traitées entre (i) l’inclusion (M0), (ii) la fin de la phase d’observation (M6) et (iii) la fin du traitement par TSS (M12) mesurée par scanner

4) Pourcentage de variation cliniquement pertinente de douleur: HEDEN pour les 2-7 ans (différence ≥ 2), échelle visuelle analogique pour les plus de 7 ans (différence ≥ 2), entre M0-M6, et M6-M12.

5) Pourcentage de variation cliniquement pertinente de qualité de vie: échelle PedsQL pour les 2 ans -18 ans (différence ≥ 5), échelle SF36 pour les plus de 18 ans (différence ≥ 20), entre M0-M6, et M6-M12.

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 6
Month 12

6 mois
12 mois

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

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

Yes

E.8.1.7.1

Other trial design description

Treatment phase preceded by a run-in period of 6 month

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

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

LVLS

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

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Centre de référence Maladies du Métabolisme du Calcium et du Phosphate
G.4.3.4	Network Country	France

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-16

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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IMP with orphan designation in the indication
Orphan Designation Number:
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