Phase I/II Randomized Controlled Trial of Umbilical Cord-derived mesenChymAl stRomal cElls in Systemic Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Measure of safety one month after first infusion
研究概览
简要总结
The purpose of this study is to test the safety and efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC) for the treatment of Systemic Sclerosis (SSc).
详细描述
A single-center, three-arm, randomized, double-blind, placebo-controlled trial is proposed. A total of 18 SSc patients will be enrolled in 3 successive blocks of 6 patients each. After being informed about the study and potential risks, all patients giving written informed consent will be randomized to one of two treatment arms or a placebo arm (total of 6 patients per arm). Within each block, the 6 patients will be randomized in a 2:2:2 ratio in one of the following arms: placebo, 1 infusion of UCMSC (M0), or 2 infusions of UCMSC (M0, M3). Second infusions of UCMSC will be performed only in the absence of Treatment Related Severe Adverse Events (TRSAE). Randomization into blocks 2 and 3 will be staggered, to allow the detection of TRSAE prior to inclusion of patients in a subsequent block, i.e. the second block will be randomized only in the absence of TRSAE one month after the first infusion of all 6 patients in block one, and similarly for the third block.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study participants, physicians (including the outcome assessors) and research nurses will be blinded to treatment arm. Only the study statistician and the personnel at the manufacturing laboratory at the Medical University of South Carolina will be aware of the subject's treatment allocation. The Medical University of South Carolina will send blinded infusion bag(s) to the Clinical Research Unit of the Jewish General Hospital.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SSc according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2103 classification criteria for systemic sclerosis
- •Severe disease defined as:
- •i) disease duration of 2 years or less with an mRss of > 20 and (ESR > 25 mm and/or hemoglobin < 11 g/dL, not explained by other causes than SSc), or ii) mRss >15 without any restriction as to disease duration plus at least one major organ involvement as defined by: a) 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); b) renal involvement consisting of past renal crisis and/or stage 2 or 3 chronic kidney disease (glomerular filtration rate between 30-89 mL/min) not explained by other causes than SSc; c) 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, conduction abnormalities (2nd or 3rd degree atrioventricular block), and/or mild to moderate pericardial effusion. All causes of organ involvement should be attributed to SSc.
- •Inadequate response (determined by patient and physician judgement) or adverse events necessitating discontinuation of standard therapy (usually consisting of methotrexate 25 mg subcutaneous (or as tolerated) per week and/or mycophenolate mofetil 2-3 gm/d (or as tolerated) for at least 3 months
- •Ineligibility or unwillingness to undergo autologous hematopoietic stem cell transplant
排除标准
- •Age < 18 years
- •Pregnancy or unwillingness to use adequate contraception
- •Life-threatening end-organ damage defined as:
- •FVC < 45% and/or 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 > 25 mmHg (and pulmonary wedge pressure < 15 mmHg) on right heart catheterization;
- •stage 4 or more chronic kidney disease (glomerular filtration rate < 30 ml/min)
- •Liver failure defined as an abnormal transaminase level (aspartate aminotransferase (ASAT), alanine aminotransaminase (ALAT) > 3 normal) unless related to activity of the disease
- •Concurrent neoplasms or myelodysplasia
- •Uncontrolled hypertension
- •Uncontrolled acute or chronic infection (HIV, HTLV-1/2 (Human T-lymphotropic virus), hepatitis B surface Ag positive, hepatitis C positive) or high risk thereof
- •Significant malnutrition with BMI < 18 kg/m2
- •Severe concomitant psychiatric disorder
- •Bone marrow insufficiency defined as neutropenia < 0.5 x 109 cell/L, thrombocytopenia < 30 x 109 cell/L, anemia < 8g/dL, CD4+ T lymphopenia < 200 x 106 cell/L due to other diseases than SSc (CD4 - cluster of differentiation 4)
- •History of poor compliance
- •Concurrent enrolment in any other protocol using an investigational drug
- •Inability to provide informed consent
研究组 & 干预措施
One infusion of UCMSC
Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of placebo at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A. Each placebo infusion will consist of a similar volume of PlasmaLyte A.
干预措施: UCMSC (Biological)
Two infusions of UCMSC
Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of UCMSC at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A.
干预措施: UCMSC (Biological)
Placebo infusions
Patients receive intravenous placebo infusions at months 0 and 3. Each placebo infusion will consist of 50 ml of PlasmaLyte A.
干预措施: Placebo (Other)
结局指标
主要结局
Measure of safety one month after first infusion
时间窗: Month 1
Treatment related severe adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification \[https://ctep.cancer.gov/protocolDevelopment/electronic\_applications/ctc.htm\]
次要结局
- Change in modified Rodnan skin score (mRss) between Month 0 and Month 12(Month 0 and Month 12)
研究者
Marie Hudson, MD
Rheumatologist, Jewish General Hospital; Physician-scientist, Lady Davis Institute for Medical Research
Sir Mortimer B. Davis - Jewish General Hospital