2023-505977-34-00招募中2 期
Phase I/II randomized clinical trial of allogeneic adipose tissue-derived mesenchymal stromal cells systemic infusion in severe systemic sclerosis MSC-AT-SSc
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- 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).
研究概览
简要总结
To evaluate the safety one month after allogeneic 2x106 MSC(AT)/kg intravenous administration once or twice at 3 months interval (M0, M3) in severe SSc patients
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase I/II randomized clinical trial of allogeneic adipose tissue-derived mesenchymal stromal cells
- 盲法
- Double (Investigator, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Provide signed and dated informed consent
- •Health insurance
- •Willing to comply with all study procedures and be available for the duration of the study;
- •Male or female, aged ≥ 18 years and ≤ 80 years of age
- •SSc patients according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 classification criteria for SSc
- •Severe disease with either: a) disease 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) mRSS ≥ 15 without any restriction as to disease duration plus at least one major organ involvement as defined by: (1) respiratory 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) renal involvement consisting of past renal crisis, microangiopathic hemolytic anemia, and/or renal insufficiency not explained by other causes than SSc; (3) cardiac 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.
- •Contraindication, inadequate response or unwillingness to undergo AHSCT (determined by patient and physician judgement)
- •Contraindication, inadequate response or unwillingness or adverse events necessitating discontinuation of conventional immunosuppressive therapy (MMF, methotrexate);
- •Women of reproductive potential must use highly effective contraception;
- •Men of reproductive potential must use condoms
排除标准
- •Age < 18 years or > 80 years
- •Severe psychiatric disorder
- •Bone marrow insufficiency, defined as neutropenia < 1 x 109/L, thrombopenia < 50 x 109/L, anemia < 8 g/dL, lymphopenia < 0,5 x 109/L
- •Inability to provide informed consent
- •Patient included in another interventional clinical trial
- •Patient under tutelle
- •Pregnancy or unwillingness to use adequate contraception;
- •Life-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
- •Active or chronic Hepatitis (ASAT, ALAT > 3 upper limit normal)
- •Neoplasms of less than 5 years, except for basal cell or in situ cervix carcinoma or concurrent myelodysplasia,
- •Uncontrolled hypertension
- •Uncontrolled acute or chronic infection
- •HIV-1 or HIV-2 infection
- •BMI < 16.5 kg/m2
结局指标
主要结局
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).
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).
次要结局
- - 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
- - Main efficacy endpoint: modified Rodnan Skin Score (mRSS) difference between M0 and M12.
- - Other efficacy disease related endpoints : o mRSS at M3, M6 and M9 o WHO 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 Forced Vital Capacity (FVC) and Diffusing capacity of Lung for carbon monoxide (DLCO) at M0, M6 and M12.
- - 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.
- - GRCS values at M3, M6, and M12.
- - CRISS values for early SSc patients at M3, M6, and M12.
- - Overall survival at M12
- - Myeloid and lymphocyte sub-populations in all included patients at M0, M1, M3, M4, M6.
- - Alloimmunization in all included patients through the detection and identification of donor-specific anti-HLA antibodies at M0, M3 and M6
- - 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.
- - 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.
研究者
Pr Dominique Farge-Bancel
Scientific
Assistance Publique Hopitaux De Paris
研究点 (3)
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