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

NCT03267277 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17016117-E-0161
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dermatomyositis; Idiopathic Inflammatory Myopathies

Keywords

Calcinosis; Dermatomyositis; Juvenile Dermatomyositis; Idiopathic Inflammatory Myopathies; Sodium Thiosulfate

Outcome Measures

Primary Outcomes (1)

• Change in Calcinosis Activity Visual Analogue Scale Score

  Calcinosis activity is defined by the metabolic activity and the inflammation associated with calcinosis. In evaluating calcinosis activity, the study physicians take into account the change in extent of calcinosis and the location of calcinosis lesions, the consistency and texture of calcinosis lesions, the presence of erythema surrounding calcinosis lesion, and any pain associated with the calcinosis lesions. A 10 cm visual analogue scale (VAS) was scored by a physician with a vertical line on the scale marking calcinosis activity where 0 cm indicates no evidence of calcinosis, and 10 cm mark indicates severe calcinosis activity. The change in calcinosis activity VAS score from week 0 to week 10 on therapy was compared to the change in calcinosis activity VAS score from week -10 to week 0 on baseline therapy. The baseline score was calculated by taking the week 0 score minus the week -10 score. The on therapy score was calculated by taking the week 10 score minus the week 0 score.

  Week 10 minus week 0 (on therapy) and week 0 minus week -10 (baseline)

Secondary Outcomes (9)

• Change in Quality of Life Measured by the Child Health Questionnaire-Parent Form 50 (CHQ-PF50): Physical Function Domain

  Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment)

• Change in Quality of Life Measured by the 36-Item Short Form Health Survey (SF-36) Score: General Health Domain

  Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment)

• Improvement of Calcinosis Lesions Measured by the Change in Mawdsley Calcinosis Questionnaire (MCQ) Score

  Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment)

• Change in Quality of Life Measured by Skindex-29 Score

  Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment)

• Change in Muscle Strength Over Time Measured by Manual Muscle Test-8 (MMT-8) Score

  Week -10 to 0 (pre-treatment); Week 0 to 10 (on treatment); Week 24 to 62 (post-treatment)

Study Arms (1)

Treatment

EXPERIMENTAL

Participants received intravenous sodium thiosulfate 16 g/m\^2 three times weekly for 10 weeks

Drug: Sodium Thiosulfate

Interventions

Sodium Thiosulfate DRUG

Sodium thiosulfate is a calcium chelator

Treatment

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, as well as creatine kinase (CK), lactate dehydrogenase (LDH), aldolase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) that are less than or equal to 2X upper limit of normal (ULN).
• If a patient has a medication for myositis changed in this window for reasons besides their myositis activity and has returned to their baseline medication use prior to enrollment they will still be eligible.

You may not qualify if:

• Is pregnant or breastfeeding
• Has known allergies to sodium thiosulfate, any of its components, or dextrose
• Has severe myositis disease activity as defined by patient/parent or physician global activity visual analogue scale score \>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

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Dermatomyositis; Myositis; Calcinosis

Interventions

sodium thiosulfate

Condition Hierarchy (Ancestors)

Polymyositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Adam Schiffenbauer
• Organization: National Institute of Environmental Health Sciences

adam.schiffenbauer@nih.gov

+1 301 451 6270

Study Officials

• Adam I Schiffenbauer, M.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: August 30, 2017
• Study Start: October 5, 2017
• Primary Completion: November 4, 2022
• Study Completion: November 9, 2023
• Last Updated: November 26, 2024
• Results First Posted: February 26, 2024

Record last verified: 2022-10

Locations

US (1)