Clinical trial NCT05947682: Manufacturing of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells for Treatment of Severe Systemic Sclerosis
Official title: Manufacturing of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells for Treatment of Severe Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Mesenchymal Stromal Cell
Systemic Sclerosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-07-17
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Mesenchymal stromal cells (MSC) are multipotent cells which carry immunomodulatory, pro-angiogenic and anti-fibrotic properties, that can target Systemic Sclerosis (SSc) pathogenesis and its clinical manifestations. The increasing use of MSC, harvested from bone marrow (MSC(M)), adipose tissue (MSC(AT)), or umbilical cord (MSC(UC)) in a variety of indications, provides consistent evidence supporting their safety in humans. The efficacy of MSC(M) intravenous (IV) injection for treating acute graft versus host disease led to their marketing approval in 2012 and MSC(AT) (Alofisel) were approved for severe Crohn's fistula in 2018.

MSC represent a promising therapeutic approach for SSc. We previously a) showed disease-specific abnormalities in MSC(M) from SSc patients, providing strong rationale to use allogeneic MSC to treat SSc patients, b) completed the first phase I/II dose escalation trial using allogenic MSC(M) infusion in 20 severe SSc patients (ClinicalTrials.gov: NCT02213705, PHRC AOM 11-250) with no safety issues, significant improvement in skin fibrosis at 3 to 6 months after infusion which appeared lower thereafter, thereby supporting the need for repeated infusions.

In vitro, experimental and clinical studies suggest that MSC properties vary according to their tissue of origin/source. We demonstrated that compared to MSC(M), MSC(AT) are easier to harvest and display higher proliferative capability before entering senescence, higher genetic stability, and superior immunosuppressive properties.

The objective of the present research is the successful production of allogeneic MSC(AT) derived from selected healthy donors, with adequate phenotypic criteria according to the International Society for Cell \& Gene Therapy.

Considering the above rationale, these MSC(AT) will subsequently be used in a Phase I/II randomized clinical trial testing allogeneic MSC(AT) systemic infusion for treatment of severe systemic sclerosis.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 and ≤ 55 years
* BMI \<30
* Non-smoker
* Admission for a pre-scheduled plastic surgery intervention liposuction or lipo-aspiration in the abdominal wall under general anesthesia
* Written consent
* Affiliated to a social security

Exclusion Criteria:

* Weight \< 50 kg
* Positive viral serology : Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Hepatitis E Virus (HEV), syphilis, Human T Lymphotropic virus (HTLV), active infection with IgM+ for toxoplasmosis, Epsiten Barr Virus (EBV), Cytomegalovirus (CMV)
* Active generalized infection (viral, parasitic, tuberculosis, leprosy...)
* Significant comorbidities according to donor health history or existing risk factors for viral infections within the past 12 months:

  * Multiple sexual partners between the donor or his or her usual partner
  * Intravenous addiction to the donor or regular partner
  * Accident of exposure to blood or derivatives suspected of being contaminated
* Uncontrolled hypertension
* Human dura mater transplant
* Surgical history of the central nervous system
* Dementia or neurological disease that may evoke subacute spongiform encephalopathy
* Family history as part of subacute spongiform encephalopathy
* Hematological malignancies
* Active or any past history of cancer
* History of chemotherapy or irradiation
* Systemic or autoimmune disease
* Multiple adenopathy, splenomegaly, hepatomegaly
* Icterus
* Haemophilia
* Known insulin-dependent diabetes
* Treatment with extractive pituitary hormones (including growth hormones)
* Steroids therapy (for more than 5 days) in the past 3 months
* Lithium treatment
* Pregnancy
* Deprived of freedom

Primary outcomes:
measure: Production of at least 3 batches of MSC(AT) derived from donors adipose tissue
timeFrame: Up to 2 months
Secondary outcomes:
measure: Percentage of viability
timeFrame: Up to 2 months
measure: Percentage of CD73+ cells
timeFrame: Up to 2 months
measure: Percentage of CD90+ cells
timeFrame: Up to 2 months
measure: Percentage of CD105+ cells
timeFrame: Up to 2 months
measure: Percentage of expression of HLA-DR
timeFrame: Up to 2 months
Other outcomes:
Locations:
Study officials:
References: