A Prospective Randomized Placebo-Controlled Double Blind Clinical Trial to Evaluate the Safety and Efficacy of CLBS03 (Autologous Ex Vivo Expanded Polyclonal Regulatory T-cells) in Adolescents With Recent Onset Type 1 Diabetes Mellitus (T1DM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 15
- 主要终点
- Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
研究概览
简要总结
This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Eligible subjects will receive a single infusion of CLBS03 (high or low dose) or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and females aged 8 to 17 years of age
- •Diagnosis of T1DM within 100 days of receipt of study drug
- •Positive for at least one islet cell autoantibody
- •Peak MMTT-stimulated C-peptide level > 0.2 pmol/mL (at the screening visit)
- •Weight of ≥30 kg
- •Must agree to use a reliable and acceptable method of contraception for the duration of participation
- •Willing and medically acceptable to postpone live vaccine immunizations for one year after infusion
- •Written informed consent and written assent
排除标准
- •Hemoglobin less than the lower limit of normal
- •Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL
- •Regulatory T-cells present in peripheral blood at <20 cells per μL
- •Current or ongoing use of non-insulin pharmaceuticals (that may affect glycemic control)
- •Current or anticipated use of systemic corticosteroids or other immunomodulatory drugs
- •Recent serious bacterial, viral, fungal, or other opportunistic infections
- •History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
- •Serologic evidence of current or past viral infection: human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and human T-lymphotropic virus (HTLV) 1/2
- •Positive QuantiFERON® tuberculosis (TB) test, purified protein derivative (PPD) skin test, history of tuberculosis, or active TB infection
- •Active infection with Epstein-Barr Virus or Cytomegalovirus
- •Liver disease
- •Pregnant or breast-feeding
- •Vaccination with a live virus within 8 weeks of receipt of study drug
- •Vaccination with a killed virus within 2 weeks of receipt of study drug
- •Participation in an investigational drug study within 90 days prior to screening
- •Previously treated with a T-Reg based cell therapy
- •History of allergy to gentamicin
研究组 & 干预措施
CLBS03 Low Dose
A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution.
干预措施: CLBS03 Low Dose (Biological)
CLBS03 High Dose
A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution.
干预措施: CLBS03 High Dose (Biological)
Placebo
A single infusion of placebo, consisting of the infusion solution only
干预措施: Placebo (Biological)
结局指标
主要结局
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
时间窗: Week 52
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
次要结局
- Change From Baseline in Mean Daily Dose of Insulin(Week 104)
- Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104(Week 104)
- Change in Hemoglobin A1c (HbA1c)(Week 104)