Evaluation of Subcutaneous Sodium Thiosulfate Pentahydrate for Ectopic Calcifications and Ossifications in Dermatomyositis, Systemic Sclerosis, and iPPSD2 Patients

The primary objective of this study is to evaluate the efficacy of a 6-month treatment with a 10% **sodium thiosulfate** (STS) solution, administered via local injections, for the treatment of ectopic calcifications and ossifications. These conditions are secondary to dermatomyositis, systemic sclerosis, and iPPSD2. The clinical relevance of this objective lies in addressing the pathological deposition of calcium in soft tissues, which can lead to significant morbidity in affected patients.

Secondary objectives include: - Assessing the evolution of ectopic calcification/ossification volume and density at three time points: at inclusion, after a 6-month run-in period, and following 6 months of STS treatment. - Evaluating the safety profile of local STS injections over the 6-month treatment period. - Determining the percentage of clinically pertinent variations in pain and quality of life after the run-in period and subsequent STS treatment.

The clinical trial involves a **study population** comprising both male and female participants, including a **vulnerable population**. The age range for participants is from 2 to 30 years for those with ectopic ossification secondary to iPPSD2, and 18 years or older for those with ectopic calcification secondary to dermatomyositis or systemic sclerosis. The sponsor has not provided the total number of participants. Participants were selected based on the presence of ectopic calcification or ossification, with the indication of STS infusion validated by a multidisciplinary committee due to significant morbidity or functional impact. Lifestyle considerations include the requirement for women of childbearing potential to use highly effective contraception, and men with partners of childbearing potential to use condoms during the treatment period and for a specified duration afterward. Participants must have no planned surgery for the calcifications or ossifications in the upcoming twelve months and must be affiliated with or beneficiaries of the social security system. Informed consent is required from all participants or their parents.

The clinical trial is designed to evaluate the efficacy of a **sodium thiosulfate pentahydrate** 10% solution when locally injected for the treatment of ectopic calcifications and ossifications. This study is a randomized, double-blind, controlled trial with a total duration of 12 months, including a 6-month run-in period followed by a 6-month treatment phase. The trial targets patients with ectopic ossification secondary to iPPSD2, or ectopic calcification secondary to dermatomyositis or systemic sclerosis. Participants will be required to attend several study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific inclusion criteria, such as age and the absence of planned surgery for the calcifications or ossifications within the next 12 months.

Following the screening, participants will enter a 6-month run-in period, during which baseline measurements will be taken. The primary endpoint is the percentage of volume evolution of the treated calcifications or ossifications, evaluated through CT-scan measurements at the end of the treatment phase. Secondary endpoints include the volume of calcifications or ossifications at various time points, adverse events, trabecular bone density, and pain associated with the treatment. Follow-up visits will occur at the end of the run-in period (Month 6) and after 6 months of treatment (Month 12) to monitor these parameters.

The expected length of participant involvement is approximately 12 months. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent. Participants are required to adhere to specific contraceptive measures during the study and for a defined period after the last injection to prevent pregnancy. The study aims to provide valuable insights into the treatment of ectopic calcifications and ossifications, contributing to the understanding and management of these conditions.

The clinical trial involves the administration of **Natriumthiosulfat 10%**, a **solution for injection/infusion**. The active substance in this experimental medication is **sodium thiosulfate pentahydrate**, which is chemically derived. The pharmaceutical form is a solution intended for injection, and the medication is administered via the injection route. The maximum daily dose is 0.7 grams, with a total maximum dose of 8.4 grams over the treatment period. The treatment duration is set for a maximum of 6 months. The product is manufactured by DR. FRANZ KÖHLER CHEMIE GMBH and is not a pediatric formulation. The medication is classified under the ATC code V03AB06, indicating its categorization as a thiosulfate.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial's main objective is to evaluate the efficacy of the 10% sodium thiosulfate solution when locally injected for the treatment of calcifications secondary to dermatomyositis and systemic sclerosis, as well as ectopic ossifications secondary to iPPSD2. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed treatment regimen.

The efficacy of the clinical trial will be assessed by evaluating the **percentage of volume evolution** of the treated calcifications or ossifications. This will be measured between the beginning (Month 6) and the end (Month 12) of the Sodium Thiosulfate (STS) treatment, specifically for each of the three conditions: dermatomyositis, systemic sclerosis, and iPPSD2. The primary endpoint will be evaluated using CT-scan measurements.

Secondary endpoints include the volume of the treated calcifications or ossifications at inclusion (Month 0), the end of the run-in period (Month 6), and after 6 months of local STS injections (Month 12), also assessed via CT-scan. Additional secondary endpoints involve the assessment of adverse events, trabecular bone density through Hounsfield units, and pain associated with STS infusion or injections. Pain will be evaluated using pain scales, with a clinically pertinent variation defined as a difference in HEDEN ≥ 2 for ages 2-7 years and a difference in VAS score ≥ 2 for those older than 7 years, measured between Month 0-Month 6 and Month 6-Month 12.

Quality of life will be assessed using appropriate scales, with a clinically pertinent variation defined as a difference in PedsQL scale ≥ 5 for ages 2-18 years and a difference in SF36 score ≥ 20 for those older than 18 years, measured between Month 0-Month 6 and Month 6-Month 12. These assessments will provide comprehensive data on the efficacy of the treatment over the specified period.