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 |
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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
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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 |
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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 |
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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
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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
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E.2.3 | Trial contains a sub-study | No |
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
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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
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- 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
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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.
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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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 6 Month 12 |
6 mois 12 mois |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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LVLS |
Dernière visite du dernier patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |