ALLOGENEIC ADIPOSE-DERIVED MESENCHYMAL STROMAL CELLS, EX-VIVO EXPANDED for Systemic sclerosis

Inclusion criteria

• {"criterion_text":"-1)\tProvide signed and dated informed consent\n-10)\tHealth insurance\n-2)\tWilling to comply with all study procedures and be available for the duration of the study;\n-3)\tMale or female, aged ≥ 18 years and ≤ 80 years of age\n-4)\tSSc patients according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 classification criteria for SSc\n-5)\tSevere disease with either: a)\tdisease duration of 2 years or less with a modified Rodnan skin score (mRSS) ≥ 20 and (abnormal CRP > 5 mg/l and/or hemoglobin < 11 g/dL), or b)\tmRSS ≥ 15 without any restriction as to disease duration plus at least one major organ involvement as defined by: (1)\trespiratory involvement consisting of lung diffusion capacity for carbon monoxide (DLCO) and/or forced vital capacity (FVC) < 80% predicted and evidence of interstitial lung disease (chest X-ray and/or high resolution computed tomography (HRCT) scan) and/or moderate Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 35 mmHg and below 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 20 mmHg and < 40 mm Hg on right heart catheterization; (2)\trenal involvement consisting of past renal crisis, microangiopathic hemolytic anemia, and/or renal insufficiency not explained by other causes than SSc; (3)\tcardiac involvement consisting of reversible congestive heart failure, atrial or ventricular rhythm disturbances such as recurrent episodes of atrial fibrillation or flutter, recurrent atrial paroxysmal tachycardia, 2nd or 3rd degree AV-block, mild to moderate pericardial effusion and/or presence of MRI involvement (Increased T1 or T2 mapping, late gadolinium enhancement, septal D sign) . All causes of organ involvement should be attributed to SSc.\n-6)\tContraindication, inadequate response or unwillingness to undergo AHSCT (determined by patient and physician judgement)\n-7)\tContraindication, inadequate response or unwillingness or adverse events necessitating discontinuation of conventional immunosuppressive therapy, except for MMF and methotrexate);\n-8)\tWomen of reproductive potential must use highly effective contraception;\n-9)\tMen of reproductive potential must use condoms"}

Exclusion criteria

• {"criterion_text":"-1.\tAge < 18 years or > 80 years\n-10.\tSevere psychiatric disorder\n-11.\tBone marrow insufficiency, defined as neutropenia < 1 x 109/L, thrombopenia < 50 x 109/L, anemia < 8 g/dL, lymphopenia < 0,5 x 109/L\n-12.\tInability to provide informed consent\n-13.\tPatient included in another interventional clinical trial\n-14.\tPatient under tutelle\n-2.\tPregnancy or unwillingness to use adequate contraception;\n-3.\tLife-threatening end-organ damage defined as: DLCO (corrected for hemoglobin) < 30% predicted; Left ventricular ejection fraction < 40% by cardiac echocardiography; Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 40 mmHg on right heart catheterization; glomerular filtration rate < 30mL/min\n-4.\tActive or chronic Hepatitis (ASAT, ALAT > 3 upper limit normal)\n-5.\tNeoplasms of less than 5 years, except for basal cell or in situ cervix carcinoma or concurrent myelodysplasia,\n-6.\tUncontrolled hypertension\n-7.\tUncontrolled acute or chronic infection\n-8.\tHIV-1 or HIV-2 infection\n-9.\tBMI < 16.5 kg/m2"}

Primary endpoints

• {"endpoint_text":"-The rate of treatment-related Severe Adverse Events (SAE) defined as Adverse Events (AE) of grade equal or above 3 using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification, at one month after each infusion (M1, M4).","definition_or_measurement_approach":"Defined as Adverse Events (AE) of grade equal or above 3 using NCI CTCAE v5.0, measured at one month after each infusion (M1 and M4)."}

Secondary endpoints

• {"endpoint_text":"-Rate of treatment-related SAE defined as AE of grade equal or above 3 CTCAE v5.0 at time and within the first 24 hours of infusion and during all follow-up at: M0, M3, M6, M9 and M12","definition_or_measurement_approach":"Measured as AE grade ≥3 per CTCAE v5.0 at infusion, within first 24 hours, and at follow-up visits M0, M3, M6, M9, M12."}
• {"endpoint_text":"-Main efficacy endpoint: modified Rodnan Skin Score (mRSS) difference between M0 and M12.","definition_or_measurement_approach":"mRSS measured at baseline (M0) and M12; primary efficacy comparison is difference M0 to M12."}
• {"endpoint_text":"-Other efficacy disease related endpoints : o\tmRSS at M3, M6 and M9 o\tWHO performance status (PS) and Health-Related Quality of Life (HRQoL) questionnaires : Scleroderma-Health Assessment Questionnaire (SHAQ), the Short Form (36) health survey (SF-36v2) and EQ-5D-5L at M0, M3, M6, and M12; o\tForced Vital Capacity (FVC) and Diffusing capacity of Lung for carbon monoxide (DLCO) at M0, M6 and M12.","definition_or_measurement_approach":"mRSS at M3/M6/M9; PS and HRQoL via SHAQ, SF-36v2, EQ-5D-5L at M0/M3/M6/M12; FVC and DLCO at M0/M6/M12."}
• {"endpoint_text":"-PFS at M12, with progression defined as any of the following: decreased in FVC > 10% or in DLCO > 15%; decrease in LVEF% > 15%; decrease in weight > 15%; decrease in creatinine clearance > 30%; increased mRSS > 25% ; and/or increase in SHAQ> 0.5.","definition_or_measurement_approach":"Progression-free survival at M12; progression defined by listed criteria (FVC, DLCO, LVEF, weight, creatinine clearance, mRSS, SHAQ thresholds)."}
• {"endpoint_text":"-GRCS values at M3, M6, and M12.","definition_or_measurement_approach":"Global Rank Composite Score measured at M3, M6, M12."}
• {"endpoint_text":"-CRISS values for early SSc patients at M3, M6, and M12.","definition_or_measurement_approach":"ACR Provisional Composite Response Index (CRISS) measured at M3, M6, M12 for early SSc subgroup."}
• {"endpoint_text":"-Overall survival at M12","definition_or_measurement_approach":"Overall survival assessed at 12 months."}
• {"endpoint_text":"-Myeloid and lymphocyte sub-populations in all included patients at M0, M1, M3, M4, M6.","definition_or_measurement_approach":"Immunophenotyping of myeloid and lymphocyte sub-populations at specified timepoints M0, M1, M3, M4, M6."}
• {"endpoint_text":"-Alloimmunization in all included patients through the detection and identification of donor-specific anti-HLA antibodies at M0, M3 and M6","definition_or_measurement_approach":"Detection and identification of donor-specific anti-HLA antibodies at M0, M3, M6 to assess alloimmunization."}
• {"endpoint_text":"-Extra-Cost per QALY (quality-adjusted Life Year) gained by unique and repeated IV infusion of allogeneic MSC(AT) in severe SSc after 12 months.","definition_or_measurement_approach":"Health economic analysis to calculate incremental cost per QALY gained at 12 months for single vs repeated IV infusion vs no treatment."}
• {"endpoint_text":"-Extra-Cost per SAE of grade above or equal to 3 CTCAE avoided by unique and repeated IV infusion of allogeneic MSC(AT) in severe SSc after 12 months.","definition_or_measurement_approach":"Economic outcome: incremental cost per SAE (grade ≥3 CTCAE) avoided at 12 months for treatment strategies."}

France

Earliest CTIS Part Ii Submission Date

21-10-2024

Latest Decision Or Authorization Date

03-04-2026

Processing Time Days

529

Number Of Sites

3

Number Of Participants

18

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France