Manufacturing of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells for Treatment of Severe Systemic Sclerosis (Pre_MSC-AT-SSc)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Sclerosis; Mesenchymal Stromal Cell
• Intervention / Treatment: Other: Adipose tissue harvesting

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominique Farge, Pr; Phone Number: +33142499768; Email: dominique.farge-bancel@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, Dr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Adults who are planned to undergo plastic surgery; Adults who are planned to undergo plastic surgery for abdominal liposuction or lipoaspiration under general anaesthetic for their own care and who are voluntary for fat donation to contribute to the study	Other: Adipose tissue harvesting; Adipose tissue harvesting (40-60g) during the abdominal liposuction or lipoaspiration under general anaesthesia which is performed according to usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Production of at least 3 batches of MSC(AT) derived from donors adipose tissue	Up to 2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of viability	Up to 2 months
Percentage of CD73+ cells	Up to 2 months
Percentage of CD90+ cells	Up to 2 months
Percentage of CD105+ cells	Up to 2 months
Percentage of expression of HLA-DR	Up to 2 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 7, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: APHP230376

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No