Cell Therapy for IBM by Muscle Injection of ADSVF (ADSVF-in-IBM)

Cell Therapy for Inclusion Body Myositis (IBM) by Muscle Injection of Autologous Uncultured Adipose-Derived Stromal Vascular Fraction (ADSVF): a Phase I Trial

Inclusion Body Myositis is a slowly but disabling myopathy, the most frequent in patients over 50 years old. No treatments (in particular immunosuppressive) are known to be efficient.

Autologous uncultured adipose-derived stromal vascular fraction (ADSVF) is recognized as an easily accessible (by a standard liposuction to obtain adipose tissue, from which ADSVF are isolated by centrifugation), safe and well tolerated source of cells with angiogenic, anti-inflammatory, immunomodulatory and regenerative properties. The purpose of our ADSVF in IBM phase I trial is to evaluate, for the first time in human diseased muscle, first the tolerance of autologous ADSVF cells locally injected in affected forearm muscles and second their capability to repair those muscles. With always the goals of tolerance first and second muscle repair, we will recruit in parallel two groups of IBM patients: the first treated by sirolimus since at least 6 months (but still disabled) and the second currently (for at least 3 months) without specific treatment for inclusion myositis.

Study Overview

• Status: Recruiting
• Conditions: Inclusion Body Myositis
• Intervention / Treatment: Biological: ADSVF

Detailed Description

The main objective of this study is to evaluate the tolerance of escalating doses of ADSVF, one month after intramuscular injection in the finger flexors, in the non-dominant forearm. The second objective of this study is to evaluate the efficacy in term of muscle repair (regenerative properties of ADSVF) and in term of muscle inflammation control, during 6 months, by functional strength tests, quantitative MRI and PBMC monitoring. This research is a phase I trial evaluating first the tolerance and second the efficacy of 3 escalating doses of ADSVF intramuscularly injected in the non-dominant forearm. The volume of injection will be of 1 ml in each of the 5 sites of the finger flexoses, in line at 1 cm apart, for a total dose of 5 millions (low dose) or 10 millions (intermediate dose) or 20 millions (high dose) of viable nucleated cells.These doses are chosen because of the perfect tolerance of intra-muscle injection of (in average) one million ADSVF per millilitre, with a total dose of viable nucleated cells injected between 2.5 and 8.6 millions.The cell treatment will be prepared from autologous uncultured Adipose-Derived Stromal Vascular Fraction (ADSVF) isolated by centrifugation of adipose tissue obtain by liposuction. The study population will be adult patients suffering of an Inclusion Body Myositis (IBM) fulfilling the Lloyd criteria treated by sirolimus since at least 6 months (but still disabled) - who are part of group 1 or currently (for at least 3 months) without specific treatment for inclusion myositis - who are part of group 2. The main inclusion criteria are : Patients: with an age ≥ 45 and ≤ 80 years old, with IBM defined by the Lloyd criteria: muscle weakness of finger flexors or quadriceps, and endomysial inflammatory infiltrates on muscle biopsy, and presence of invaded fibers or rimmed vacuoles on muscle biopsy, who gave their written informed consent, affiliated to a social security regime (expected AME) ; and for: group 1: treated by sirolimus since at least 6 months (but still disabled ) - group 2: currently (for at least 3 months) without specific treatment for inclusion myositis - group 2. The duration of participation of the patients will be 7 months, included one month between maximum the inclusion visit and the injection visit, and 6 month of follow-up periof after ADSVF injection.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Olivier Benveniste, Professor; Phone Number: 01 42 16 10 88; Email: olivier.benveniste@aphp.fr
• Study Contact Backup: Name: Anne Radenne, Manager; Phone Number: 01 42 16 16 99; Email: anne.radenne@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Olivier Benveniste
    • Contact: Olivier BENVENISTE; Phone Number: 0142161699
    • Contact: Anne RADENNE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• With an age ≥ 45 and ≤ 80 yo.
• Man or menopausal woman. - With IBM defined by the Lloyd criteria (Lloyd et al., 2014): muscle weakness of finger flexors or quadriceps, and endomysial inflammatory infiltrates on muscle biopsy, and presence of invaded fibers or rimmed vacuoles on muscle biopsy.
• Who gave their written informed consent
• Affiliated to a social security regime (expected AME) And for: -group 1: treated by sirolimus since at least 6 months (but still disabled ) - group 2: currently (for at least 3 months) without specific treatment for inclusion myositis.

Exclusion Criteria:

• Impossibility to walk 10 meters
• Grip evaluated by MRC5 MMT at 0 OR 1.
• Body mass index < 18
• Not able to stop any anticoagulant, or antiaggregant drugs within the week before and the 48 hours before the liposuction
• Severe respiratory insufficiency (FVC < 50% and/or FEV1 < 50%)
• Severe chronic kidney disease (Estimated Glomerular Filtration Rate < 15 ml/min and/or proteinuria > 0.5 g/24h)
• Cancer non in remission (necessitating specific treatment) during the past 12 months
• Connective Tissue Disease non in remission (necessitating specific treatment) during the past 12 months - Bone marrow transplantation
• Connective Tissue disease non in remission (necessitating specific treatment) during the past 12months - Immunosuppressive drugs except sirolimus, ongoing or stopped in less than 3 months
• Polyvalent immunoglobulins (IV or sub-cut) ongoing or stopped in less than 3 months
• Any biotherapies (mAbs) such as ant-CD20, CTLA4Ig, anti-TNF, anti-IL6R, anti-IL1 etc… ongoing or stopped in less than 6 months.
• Seropositivity for HIV, HCV or HBV
• Contraindication to muscle MRI
• Contraindications to the liposuction: eg coagulation disorders, etc… - Contraindications to anaesthetics
• Documented conventional antibiotics severe allergy such as ß-lactam (cephalosporin), cyclins, macrolides (for example metronidazole), quinolones
• Participation in another trial (Jardé 1 or Jardé 2)
• Legal protection (curatorship or tutorship) or safety measure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Group 1: Patients treated by sirolimus since at least 6 months (but still disabled) Group 2: Patients currently (for at least 3 months) without specific treatment for inclusion myositis	Biological: ADSVF; Group 1 and 2 : Escalating dose of ADSVF injection (5 millions of cells, 10 millions of cells and 20 millions of cells).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In each group, tolerance of escalating doses (3+3) of ADSVF in the non-dominant forearm	By determining the dose-limiting toxicity (DLT)	Days 0 (day of the injection) to day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In each group, tolerance of escalating doses (3+3) of ADSVF in the non-dominant forearm	By research of adverse events	Days 0 (day of the injection) to 6 months (end of participation)
In each group, efficacy in term of muscle repair (regenerative properties of ADSVF)	Functional muscle evaluations	At day 30, 3 month and 6 month
In each group, efficacy in term of muscle repair (regenerative properties of ADSVF)	Muscle mass, fatty replacement and inflammation by quantitative NMRI	At 6 month
In each group, evaluation of muscle inflammation control	Immunomonitoring of the peripheral blood mononuclear cells (PBMC)	At 6 month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Olivier Benveniste, Professor, APHP

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cell Therapy; Inclusion Body Myositis; ADSVF
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Myositis, Inclusion Body
• Other Study ID Numbers: APHP180593; 2020-005876-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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