Treatment of systemic lupus erythematosus by injection iv of mesenchymal stem cells (MSC-LES)

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2017-001400-29-FR
• Date of registration: 31/07/2018
• Prospective Registration: No
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
• Public title: Treatment of systemic lupus erythematosus by injection iv of mesenchymal stem cells (MSC-LES)
• Scientific title: Treatment of severe refractory systemic lupus erythematosus by injection of allogeneic mesenchymal stem cells derived from the umbilical cord - MSC SLE - MSC-LES
• Date of first enrolment: 16/03/2018
• Target sample size: 10
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001400-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: monocentric, phase II; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCI Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

• Name: DRCI Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects:
1- Pregnancy, breastfeeding or lack of appropriate contraception during study duration
2- Presence of:
a) Renal failure: calculated creatinine clearance of <30 ml / min
b) Cardiac failure: clinical signs of congestive heart failure; left ventricular ejection fraction <40% on echocardiography; uncontrolled ventricular arrhythmia;
c) Hepatitis defined by abnormal levels of transaminases (AST, ALT> 2 x normal) not related to disease activity.
d) Respiratory disease: mean PAP> 50 mmHg (echocardiography), respiratory failure defined by a resting blood pressure of oxygen at PaO 2 < 70 mmHg and / or PaCO2 > 50 mmHg without oxygen
3- Severe psychiatric disorders, including severe psychosis related to SLE, which would prevent to give informed consent or to undergo the procedure.
4- Active neoplasia or concomitant myelodysplasia, except for basal cell carcinoma or squamous cell carcinoma or in situ cervix carcinoma.
5- Bone marrow failure defined by neutropenia <0.5.109/L, thrombocytopenia <30. 109 / L, anemia < 8 g / dL, lymphopenia CD4 + <200 x 106 / L caused by another disease than SLE.
6- Acute or chronic uncontrolled infection: HIV 1/2, HTLV-1/2, Hepatitis B (HBsAg surface antigen), Hepatitis C with positive PCR
7- Patient having received belimumab within 2 months of belimumab within 2 months of Baseline, or having received rituximab or other B cell depleting biologic therapy within 6 months of Baseline
8- Current substance abuse or recent (within 60 days) history of substance abuse
9- Patient in periods of exclusion from the national roster of researchers
10- Patient with Linguistic or psychological incapacity to sign informed consent
11- Patient already included in another study at the same time.
12- Poor patient compliance.
13- Patient under legal protection.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
Subjects:
1- Pregnancy, breastfeeding or lack of appropriate contraception during study duration
2- Presence of:
a) Renal failure: calculated creatinine clearance of <30 ml / min
b) Cardiac failure: clinical signs of congestive heart failure; left ventricular ejection fraction <40% on echocardiography; uncontrolled ventricular arrhythmia;
c) Hepatitis defined by abnormal levels of transaminases (AST, ALT> 2 x normal) not related to disease activity.
d) Respiratory disease: mean PAP> 50 mmHg (echocardiography), respiratory failure defined by a resting blood pressure of oxygen at PaO 2 < 70 mmHg and / or PaCO2 > 50 mmHg without oxygen
3- Severe psychiatric disorders, including severe psychosis related to SLE, which would prevent to give informed consent or to undergo the procedure.
4- Active neoplasia or concomitant myelodysplasia, except for basal cell carcinoma or squamous cell carcinoma or in situ cervix carcinoma.
5- Bone marrow failure defined by neutropenia <0.5.109/L, thrombocytopenia <30. 109 / L, anemia < 8 g / dL, lymphopenia CD4 + <200 x 106 / L caused by another disease than SLE.
6- Acute or chronic uncontrolled infection: HIV 1/2, HTLV-1/2, Hepatitis B (HBsAg surface antigen), Hepatitis C with positive PCR
7- Patient having received belimumab within 2 months of belimumab within 2 months of Baseline, or having received rituximab or other B cell depleting biologic therapy within 6 months of Baseline
8- Comorbidities requiring corticosteroid therapy
9- Current substance abuse or recent (within 60 days) history of substance abuse
10- Patient in periods of exclusion from the national roster of researchers
11- Patient with Linguistic or psychological incapacity to sign informed consent
12- Patient who has already been included in this or another study at the same time.
13- Poor patient compliance.
14- Patient under legal protection.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of Systemic Lupus Erythematosus refractory to standard treatments.
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: ALLOGENEIC MESENCHYMAL STROMAL CELLS DERIVED FROM THE UMBILICAL CORD
Product Code: 0
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: 0
CAS Number: 0
Current Sponsor code: P150302
Other descriptive name: CSM allogéniques issues de cordons ombilicaux ( MTI-PP)
Concentration unit: 1X 100 milligrams/millilitre
Concentration type: range
Concentration number: 1.106-4.106

Primary Outcome(s)

Main Objective: To analyze the tolerance of the administration of allogeneic CSM in the treatment of systemic Lupus Erythematous System (SLE) refractory to conventional treatments (Cyclophosphamide (CY), MMF or corticosteroids with or without corticosteroids)

Timepoint(s) of evaluation of this end point: No

Secondary Objective: 1- Feasibility of the administration of allogeneic CSM in the treatment of refractory patients with refractory severe prior conventional treatments
2- Tolerance at more than three months after injection, taking into account the morbidity observed and the overall survival of patients with SLE treated up to 1 year after the procedure (with 1 year of follow-up after the end of the study ).
3- Analysis of clinical and biological response according to clinico-biological criteria for routine surveillance of lupus by functional scores (SELENA-SLEDAI, BILAG, SF36, EQ5D, SRI, SLICC-SLE)
4- Analysis of the efficacy at 3 months of injection of allogeneic MSCs by evaluating the proportion of patients presenting a Major Clinical Response (MCR).
5- Evaluate the percentage of patients with Partial Clinical Response (CPR) during the 12-month follow-up period of the study.
6- Evaluation of the immunomodulatory action

Primary end point(s): Immediate tolerance assessed during the injection and the first 10 days after the injection of the allogeneic MSCs, according to the side effects defined by the CTCAE standards.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: No

Secondary end point(s): 1-Feasibility of administering allogeneic MSCs in the treatment of refractory patients with refractory severe prior conventional treatments
2-Tolerance at more than three months after injection, taking into account the morbidity observed and the overall survival of SLE patients treated up to 1 year after the procedure (with 1 year of follow-up after the end of the study ).
3-Analysis of clinical and biological response according to clinico-biological criteria for routine lupus surveillance by functional scores (SELENA-SLEDAI, BILAG, SF36, EQ5D, SRI, SLICC-SLE)
4-Analysis of the efficacy at 3 months of injection of allogeneic MSCs by evaluating the proportion of patients presenting a Major Clinical Response (MCR).
5-Evaluate the percentage of patients presenting a Partial Clinical Response (CPR) during the 12 months of study follow-up.
6-Evaluation of immunomodulatory action

Secondary ID(s)

P150302J

Source(s) of Monetary Support

Fondation du Rein (FdR) sous égide de la FRM, en partenariat avec l’AFM Téléthon et l’AIRG