Phase 3 N=14 Treatment

Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis

Dermatomyositis · Idiopathic Inflammatory Myopathies

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View on ClinicalTrials.gov: NCT03267277 ↗

Enrolled (actual)

Serious AEs

42.9%

Results posted

Feb 2024

Primary outcome: Primary: Change in Calcinosis Activity Visual Analogue Scale Score — -3.45 Units on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Sodium Thiosulfate (Drug)
Age: Pediatric, Adult, Older Adult · 7+ yrs
Sex: All
Sponsor: National Institute of Environmental Health Sciences (NIEHS)
Primary completion: Nov 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Calcinosis Activity Visual Analogue Scale Score	-3.45	—
SECONDARY Change in Quality of Life Measured by the Child Health Questionnaire-Parent Form 50 (CHQ-PF50): Physical Function Domain	-1.00; -8.00	—
SECONDARY Change in Quality of Life Measured by the 36-Item Short Form Health Survey (SF-36) Score: General Health Domain	2.50; -1.00; -8.00	—
SECONDARY Improvement of Calcinosis Lesions Measured by the Change in Mawdsley Calcinosis Questionnaire (MCQ) Score	0.33; -0.74; -0.17	—
SECONDARY Change in Quality of Life Measured by Skindex-29 Score	1.77; -8.15; -0.38	—
SECONDARY Change in Muscle Strength Over Time Measured by Manual Muscle Test-8 (MMT-8) Score	-0.08; 1.38; -0.27	—
SECONDARY Change in Muscle Strength Over Time Measured by Quantitative Muscle Assessment (QMA): Hip Abductor Muscle	0.16; 0.74; 1.35	—
SECONDARY Change in Myositis Activity Measured by Physician Global Activity (PGA)	0.36; -0.87; -0.32	—
SECONDARY Change in Myositis Damage Measured by Physician Global Damage (PGD)	-0.02; -1.07; -0.18	—
SECONDARY Change in Total Percent Body Surface Area (BSA) Involved With Calcinosis	2.79; -10.18; -0.45	—

Summary

Background: Dermatomyositis (DM) and juvenile dermatomyositis (JDM) cause inflammation in the muscles. People with DM and JDM can develop calcium deposits in places they should not, known as calcinosis. Calcinosis can be painful and cause disabilities and other problems. Researchers want to learn more about calcinosis to find treatments for it. Objective: To test if sodium thiosulfate (STS) can treat people with DM with calcinosis. Eligibility: People ages 7 and older who have moderate or severe calcinosis. They must have stable DM and calcium deposits in the torso or at least 2 limbs. Design: Participants will be screened with: * Medical history * Physical exam * Muscle strength and function tests * Blood and urine tests Participants will have several visits: * 7-day pre-treatment visit about 10 weeks before starting STS * Treatment visits over 10 weeks. They will get STS 3 times a week through IV infusion. They may be hospitalized the whole time. If they tolerate the drug, they may be discharged at certain times. During these times, they will return for the infusions. * 3- to 5-day post-treatment visits 24 weeks and 62 weeks after starting STS. Visits may include repeats of screening tests and: * Questionnaires * Scans: They lie in a machine that takes pictures of the body. They may be injected with a radioactive agent. * Durometry: A small instrument applies pressure on the skin or exposed calcinosis. * Measurements of blood flow in the arms and fingernail blood vessels * Photographs of the skin * Kidney ultrasound * Tests of kidney function * Calcinosis aspiration: A needle placed into areas of calcinosis removes liquid.

Eligibility Criteria

INCLUSION CRITERIA:
At least 7 years of age
Meets Bohan and Peter criteria, as modified by the International Myositis Assessment and Clinical Studies Group (IMACS), for probable or definite DM or JDM
Has extensive calcinosis, defined as calcinosis involving at least 2 extremities or the torso
Has moderate to severe calcinosis, defined as having a calcinosis activity visual analogue scale score of greater than or equal to 3.5 cm out of 10 cm
Is willing and able to comply with the requirements of the protocol and to undergo all testing
Can have IV access established to receive study infusions
Myositis disease activity is stable*
Medications for myositis are stable for at least 6 weeks prior to study entry**
Men and women of reproductive potential must agree to use a reliable form of birth control during the 62-week duration of the study
Subjects or their legal guardian must sign a written informed consent
Stable myositis disease activity will be defined by physician global and patient/parent global VAS that are 4 cm out of 10 cm
Has had an escalation of immunosuppressive therapy in the 2 months prior to enrollment for the purpose of treating active myositis disease activity, including the addition of a new agent to treat the patients underlying disease or an increase in dose of an existing medication used to treat the patient's disease (other than an adjustment for weight or body surface area in children)
Has a malignancy or had a malignancy within 5 years of diagnosis of their DM (except for benign skin lesions or basal cell carcinoma)
Known or suspected history of alcohol or drug abuse in the 6 months prior to study enrollment
Has systemic lupus erythematosus, scleroderma, or a condition other than DM that is associated with calcinosis as a complication
Has had a change in medications used specifically for calcinosis in the 2 months prior to enrollment, including but not limited to alendronate, etidronate, pamidronate, probenecid, colchicine, diltiazem, thalidomide, and aluminum hydroxide
Has used probenecid, diltiazem, aluminum hydroxide, or hydrochlorothiazide in the 2 months prior to enrollment
Has currently or has a history of any of the following: heart failure, renal impairment (GFR less than 30 representing severe renal disease), liver disease (Child-Pugh class C), arrhythmias (that are symptomatic or are concerning for progression to symptomatic arrhythmias), or recurrent kidney stones (more than one episode of symptomatic kidney stones separated by at least 1 month), or QT prolongation, or hypocalcemia, or metabolic acidosis, or hypotension
Has severe osteoporosis or has had a bone fracture within a year prior to enrollment. For adults, severe osteoporosis as defined by the World Health Organization (WHO) as bone mineral density (BMD) 2.5 standard deviations below that of a young, normal adult (T-score at or below -2.5 and one or more fractures). For individuals, less than age 18, severe osteoporosis as defined by the First Pediatric Consensus Development Conference as a Z-score below -2 and one or more fractures.
Has a psychiatric illness or medical non-compliance that the study team feels will make the patient unlikely to complete the study
Has dysphagia where non-oral feeding alternatives are needed.
Requires supplemental oxygen therapy
Has >3 episodes of cellulitis requiring IV antibiotics related to calcinosis within a year prior to enrollment or cellulitis within 1 month of enrollment
Previously received or currently receiving sodium thiosulfate by any route
Is on an oral prednisone dose of more than 1mg/kg/day or other oral corticosteroid equivalent.
Is taking any concomitant medications that are thought to alter sodium thiosulfate s effects or pharmacokinetics. Once patients have met all other inclusion criteria and no other exclusion criteria this criteria will be checked. A PharmD will evaluate the patient's current me

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Data sourced from ClinicalTrials.gov (NCT03267277). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.