Calcinosis cutis in SSc patients treated with sodium thiosulfate assessed by biomarkers and imaging

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus Universitetshospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

21 Jun 2024 → ongoing

Decision date (initial)

2024-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

This is a prospective, multi-centre, investigator-initiated randomized controlled study, with the overall objective of evaluating the efficacy and safety of intralesional sodium thiosulfate (STS) treatment in patients with calcinosis cutis (CC). The primary aim is to assess remission (complete/partial) in CC lesions during treatment with STS.

Secondary objectives 10

1. to assess treatment efficacy of intralesional STS
2. to quantify change in CC lesion severity with patient- and physician global score, PtGA and PhGA
3. to quantify change in CC lesion seen on imaging (RCM, DECT, and CBCT): size, density, remission
4. to compare efficacy of various imaging modalities (RCM, DECT, and CBCT)
5. to compare imaging (RCM, DECT, and CBCT) findings to clinical evaluation and radiographies (the radiological scoring system)
6. to perform clinical assessment: ulcer size, inflammatory surroundings and clinical photos
7. to assess safety
8. to analyse changes in in biomarkers, measured by blood and skin analyses
9. to investigate patient QoL
10. to explore CC lesions and volume in PET/MRI imaging

Conditions and MedDRA coding

Calcinosis cutis in systemic sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. SSc fulfilling ACA/EULAR 2013 criteria as well as patients with positive U1RNP and mixed connective tissue disease with overlap syndrome to SSc
2. Provides signed, written informed consent
3. Above 18 and under 90 years of age at baseline
4. Legally competent, able to give verbal, written and informed consent
5. Communicate in Danish verbally as well as in writing
6. Subject in good general health and willing to participate
7. Is willing and able to comply with the requirements of the protocol and to undergo all testing
8. Medications for SSc are stable for at least 6 weeks prior to study entry
9. If subjects received STS treatment on the selected lesion before, a washout period of 3 months must be complete upon study entry

Exclusion criteria 7

1. Individuals with other skin diseases in the skin area of interest
2. Individuals with CC of other causality
3. Individuals whose CC lesion is not accessible for imaging e.g., inside the ear, inside nostrils.
4. Pregnancy
5. Breastfeeding
6. Women of child-bearing potential not using a contraceptive agent at the time of inclusion
7. Known hypersensitivity to STS

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Complete remission of CC from week 0 to week 28 [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ] defined as removal of total calcinosis volume in scans and/or clinical complete clearance
2. Partial remission of CC from week 0 to week 28 [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ] defined as partial removal of calcinosis volume in scans and/or clinical improvement in PtGA score

Secondary endpoints 10

1. Assessment of treatment efficacy of intralesional STS [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ]
2. Change in CC lesion severity patient- and physician global score, PtGA and PhGA (1-10) [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ]
3. Change in CC lesion seen on imaging (RCM, DECT, and CBCT): size, density, remission (complete/partial) [ Time Frame: Week 1, week 28 ]
4. Comparison of imaging modalities to assess change in CC (RCM, DECT, and CBCT) [ Time Frame: Week 1, week 28 ]
5. Validation of/comparison to the Radiological scoring system for CC [ Time Frame: Week 1, week 28 ] The Radiological scoring system for CC is a newer scoring system to assess severity of CC affecting the hands in patients with SSc developed by the Scleroderma Clinical Trials Consortium. Currently, no standardised outcomes for CC exist. This novel radiographic scoring system accounts for the area coverage, density, and anatomic location of CC affecting the hands in patients with SSc
6. Clinical assessment: ulcer size, inflammatory surroundings and clinical photos [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ]
7. Changes in biomarkers, measured by blood and skin analyses (e.g., to evaluate changes due to therapy, or differences between responders and non-responders to therapy) [ Time Frame: Week 1, week 5, week 17, week 28 ]
8. Incidence and severity of adverse events, including laboratory abnormalities, over time [ Time Frame: Week 1, week 5, week 17, week 21, week 28 ]
9. QoL outcome: Health Assessment Questionnaire Disability Index (MD-HAQ-) [ Time Frame: Week 1, week 28 ]
10. Change in total calcinosis volume and demonstration of PET/MRI imaging of CC lesions [ Time Frame: Week 28 ]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus Universitetshospital

Sponsor organisation

Aarhus Universitetshospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus Universitetshospital

Contact name

Anne Braae Olesen

Public contact point

Organisation

Aarhus Universitetshospital

Contact name

Anne Braae Olesen

Third parties 2

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications