Efficacy and safety of allogenic cultured Adipose-derived mesenchymal stromal cell injections on MoUth fibrosis and handicap in patients with Systemic sclEroderma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2025-08-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess efficacy of allogenic cultured adipose-derived stromal cell injections on orofacial fibrosis and handicap at week 12 in patients with systemic scleroderma, as measured by the MHISS scale.

Secondary objectives 17

1. To assess safety of allogenic cultured adipose-derived stromal cell injections
2. To evaluate the efficacy on oral function, measured by mouth perimeter and interincisal distance
3. To evaluate the efficacy on orofacial handicap, assessed by the 3 subscales of the MHISS
4. To evaluate the efficacy on handicap and quality of life
5. To evaluate the effect on oral habits and hygiene
6. To evaluate the effect on oral microbiota (only at Toulouse)
7. To evaluate the efficacy on Plaque index (only at Toulouse)
8. To evaluate the efficacy on DMFT (decayed missing filled teeth) and Panoramic x-ray
9. To evaluate the efficacy on oral function assessed by mandibular tracking and articular and neuro-muscular activity study (only at Toulouse)
10. To evaluate the impact of the vision and the occlusion on the postural parameters by stabilometry (only at Toulouse
11. To evaluate the potential link between psycho-social aspects and oro-facial pain
12. To evaluate the efficacy on skin fibrosis assessed by modified Rodnan Skin Score (mRSS)
13. To evaluate the efficacy on dry mouth syndrome
14. To evaluate the efficacy on aesthetics, assessed by Standardized two-dimensional photographs or face scan at Toulouse
15. To perform an immunomonitoring of vascular and antifibrotic biomarkers
16. To constitute a serum and plasma biobank
17. To constitute an oral microbiota biobank (salivary and periodontal) (only at Toulouse)

Conditions and MedDRA coding

Systemic sclEroderma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female patient ≥18 years of age
2. Patient with systemic scleroderma according to the 2013 ACR/EULAR classification criteria
3. Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20 (0–48)
4. Rodnan skin score on the face more than or equal to 1
5. Maximal mouth opening of less than 40 mm (distance between the dental arches)
6. Patient must have provided written informed consent prior to enrolment
7. Patient must be able to understand the requirements of participating in the protocol
8. Patient affiliated to a social security system

Exclusion criteria 10

1. Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months
2. Injection of botulinum toxin within 4 weeks prior to “inclusion visit”
3. Patient who underwent autologous hematopoietic stem cell transplantation (HSCT) within less than 1 year
4. Local active labial herpes virus within 1 week prior to “inclusion visit”,
5. Patients with an indication for intensification by autologous HSCT (according to EBMT guidelines and national MATHEC-SFGMTC guidelines),
6. History of cancer in the last five years, except for successful excised basal cell/squamous cell carcinoma, or successfully excised early melanoma of the skin. Subjects, who had successfully tumor resection or radiation or chemotherapy more than 5 years prior to inclusion and no recurrence, may be enrolled in the study,
7. Radio- or chemotherapy in progress
8. Females who are pregnant or breastfeeding or plan to be or do so during the course of this study,
9. Women of childbearing potential (WOCBP) who are sexually active and unwilling to use an adequate birth control method
10. Vulnerable patients (persons deprived of their liberty by judicial or administrative decision, persons undergoing psychiatric treatment, persons admitted to a health or social establishment for purposes other than research) according to article L1121-6 of the Public Health Code)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the change in the Mouth Handicap in Systemic Sclerosis scale (MHISS) between baseline and week 12; An improvement of at least 5 points will be considered clinically significant

Secondary endpoints 17

1. The safety throughout the course of the study (until week 24 since baseline) will be assessed by monitoring adverse events, serious adverse events and injection site reactions
2. Change in maximum interincisal distance and mouth perimeter
3. Change in Opening, Dryness and Aesthetic of the 3 subscales of the MHISS;
4. Change in patient-reported outcomes (patient satisfaction assessment (the patients will be asked to fill in a simple questionnaire where their degree of satisfaction could be expressed by a semiquantitative score (unsatisfied, mildly/moderately satisfied, rather satisfied, and very satisfied), sHAQ, OHAT, BOFA questionnaire and EQ-5D-5L at W4, W12 and W24;
5. Change in oral habits and hygiene measured by oral health and hygiene questionnaire at W24
6. Change in oral microbiota (only at Toulouse) at W12 and 24
7. Change in Plaque index (reflecting the ability to maintain oral hygiene) at W12 an W24 (only at Toulouse),
8. Change in DMFT (decayed missing filled teeth) and Panoramic x-ray at W24;
9. Change in mandibular tracking (only at Toulouse at W4, W12 and W24 and articular and neuro-muscular activity (only at Toulouse) at W12 and W24
10. Change posture by stabilometry (only at Toulouse) at W12 and W24
11. Change in psycho-social aspects and oro-facial pains by EDAS21, Epworth at W4, W12 and W24 and Combadazou-Destruhaut questionnaire (only at Toulouse) at W12 and W24 and drawings of consciousness (only at Toulouse) at W24
12. Change in modified Rodnan skin score at W12 and W24;
13. Change in dry mouth syndrome at W4, W12 and W24 (Change in Xerostomia Inventory questionnaire; Change in Salivary flow; Change in the salivary pH
14. Change in Standardised two-dimensional photographs or facial scan at Toulouse at W4,12 and 24
15. Change in immunomonitoring of vascular and antifibrotic biomarkers expression at W12;
16. Not an evaluation criterion but the creation of a serum, plasma biobank at baseline, W12 and W24).
17. Not an evaluation criterion but the creation of oral microbiota biobank (only at Toulouse at W12 and W24)

Investigational products

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

Test 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

clinical research project manager

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

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

Documents 9 files

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

Application history

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