Systemic sclerosis: ADUSE

### **TRANSLATION**

#### **SPONSOR**: CHU de Toulouse

#### **PRINCIPAL INVESTIGATOR/COORDINATOR:**
**Prof. Grégory PUGNET**
Department of Internal Medicine and Clinical Immunology,
CHU Rangueil, 1 avenue du Pr Jean Poulhès,
31059 Toulouse Cedex 9
Tel: +33 5 61 32 35 95 / Fax: +33 5 61 32 29 09
Email: pugnet.g@chu-toulouse.fr

#### **Biotherapy Module CIC 1436 Toulouse:**
Hôpital Rangueil, 1 Avenue Jean Poulhès,
31059 Toulouse Cedex 9
**Contacts:** Marine LEBRIN-SERRENTINO, Laetitia BUGAREL, Fabian GROSS
Tel: +33 5 61 32 37 24
Emails: lebrin.m@chu-toulouse.fr; bugarel.l@chu-toulouse.fr; gross.f@chu-toulouse.fr

### **TITLE:**
Injection of autologous mesenchymal stem cells derived from adipose tissue for the treatment of digital ulcers in systemic sclerosis.

**CLINICALTRIALS:** NCT04356755

### **JUSTIFICATION / CONTEXT**
The hypothesis of our A-DUSE study is that the digital injection of cultured allogeneic stromal cells derived from adipose tissue (CellReady®) could promote the healing of refractory ischemic digital ulcers (DU) induced by systemic sclerosis, in a clinical context where no validated alternative treatment is available. These cells may also have a preventive effect on the occurrence of new digital ulcers.

### **OBJECTIVE**

#### **Primary Objective:**
The main objective of this study is to compare the efficacy and safety at 16 weeks of allogeneic ASC digital injections versus placebo for the healing of active refractory ischemic digital ulcers (chronic and/or recurrent within three months of ulcer onset) in patients with systemic sclerosis.

#### **Secondary Objectives:**
– Evaluate the effectiveness of local allogeneic ASC injections on ulcer healing, the absence of complications or new ulcers, as well as their impact on quality of life and pain scale assessment.
– Assess the immunomodulatory and angiogenic activity of the injected ASCs.
– Characterize the phenotype and cytokine profile of the injected ASCs.
– Conduct immunomonitoring of vascular biomarkers and establish a biobank of serum and plasma samples.

### **TRIAL PROCEDURE**

### **INCLUSION CRITERIA**
– Adult patients over 18 years old with systemic sclerosis meeting the 2013 ACR/EULAR criteria.
– Patients with at least one active ischemic digital ulcer located beyond the proximal interphalangeal joint (but not on subcutaneous calcifications or bony prominences) that remains refractory after **10 ± 2 weeks** of standard treatment, following the **PNDS Scleroderma** guidelines.

### **NON-INCLUSION CRITERIA (non-exhaustive list)**

#### **Patient-related exclusions:**
– Patients currently on statins, vasodilators, calcium channel blockers, ACE inhibitors, nitroglycerin, α-adrenergic blockers, angiotensin II receptor antagonists, N-acetylcysteine, or low-molecular-weight heparin within the last three months or without stable dosage for at least one month.
– Patients on systemic antibiotics (oral or IV) for infected digital ulcers within the last four weeks.
– Local botulinum toxin injection in any finger within the last four weeks.
– Upper limb surgical sympathectomy or ulcer debridement within the last month.
– Patients who have undergone an autologous hematopoietic stem cell transplant (HSCT) within the past 12 months.
– Patients with an indication for HSCT intensification.
– History of cancer within the last five years.

#### **Ulcer-related exclusions:**
– Digital ulcers caused by conditions other than systemic sclerosis, non-ischemic ulcers, ulcers with osteomyelitis or clinically uncontrolled infection, ulcers requiring systemic antibiotic therapy, or ulcers requiring urgent surgical intervention.

### **RESEARCH METHOD:**
A **Phase II**, **multicenter, prospective, randomized, placebo-controlled** study. Patients will be followed for **16 weeks**.