A Double-blinded, Randomized, Parallel, Placebo-controlled Trial of Wharton's Jelly-derived Allogeneic Mesenchymal Stromal Cells to Treat Type 1 Diabetes in Children and Adolescents
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Safety at one year evaluated as adverse events
研究概览
简要总结
This is a combined phase 1 and 2 study in 66 subjects, male or female, between 7-21 years of age that have recently (< 6 months) been diagnosed with type 1 diabetes. The first phase 1 part of the study includes six subjects openly receiving allogeneic Wharton's jelly derived mesenchymal stromal cells as the Advanced Therapy Medicinal Product (ATMP) Protrans, three each in the age ranges 7-11 and 12-18.The second part is a randomized, double-blinded placebo-controlled phase 2 study in parallel design comparing allogeneic Wharton's jelly derived mesenchymal stromal cells treatment (as Protrans) to placebo in children and adolescent subjects (7-21 years of age) diagnosed with type 1 diabetes, The primary objectives of this study will be to investigate the safety, tolerance and efficacy after an allogieneic infusion of Wharton's jelly derived mesenchymal stromal cells.
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)
入排标准
- 年龄范围
- 7 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent for participation of the study (for subjects below 18 years of age also from both caregivers), given before undergoing any study-specific procedures
- •Clinical history compatible with type 1 diabetes diagnosed less than 6 months before enrolment
- •In the first part of the study, six subjects, three between 7-11 and three between 12-18 years of age (both groups inclusive at both ends), will be included. The sixty subjects in the second part of the study are stratified by age (12-21 and 7-11 years, respectively) and randomized to one of two treatment arms (active or placebo), with a 6-month safety delay for the younger stratum.
- •Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
- •Fasting plasma C-peptide concentration >0.12 nmol/L.
- •Subjects of child-bearing potential must agree to using adequate contraception until one year after the administration of WJMSC/Placebo. Adequate contraception is as follows:
- •oral (except low-dose gestagen (lynestrenol and noretisteron), injectable or implanted hormonal contraceptives.
- •intrauterine device
- •intrauterine system (for example progestin-releasing coil)
- •vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)
排除标准
- •Subjects with body weight >100 kg
- •Subjects with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
- •Subjects with uncontrolled hypertension (≥160/105 mmHg).
- •Subjects with active on-going infections.
- •Subjects with latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or has traveled in areas with a high risk of tuberculosis or mycosis within the last 3 months.
- •Subjects with serological evidence of infection with HIV, Treponema pallidum, hepatitis B antigen (subjects with serology consistent with previous vaccination and a history of vaccination are acceptable), or hepatitis C.
- •Subjects with any systemic immune suppressive treatment
- •Subjects with a known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- •Subjects with known, or previous, malignancy.
- •Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin.
- •Subjects with GFR <60 ml/min/1.73 m2 body surface.
- •Subject with any condition or any circumstance that, in the opinion of the investigator, would make it unsafe to undergo treatment with MSC.
- •Known hypersensitivity against any excipients, i.e., dimethyl sulfoxide (DMSO).
研究组 & 干预措施
Wharton's jelly derived mesenchymal stromal cells (Protrans)
Cells are dissolved in saline and given intravenously over a period of 20-40 min. 100 million cells to subjects < 50 kg and 200 million cells to subjects 50-100 kg (>100 kg is an exclusion criterion).
干预措施: the ATMP Protrans (Biological)
Placebo
Placebo (saline) is given intravenously over a period of 20-40 min.
干预措施: the ATMP Protrans (Biological)
结局指标
主要结局
Safety at one year evaluated as adverse events
时间窗: One year
Safety parameters will be evaluated at each study visit and recorded as adverse events.
Safety at five years evaluated as adverse events
时间窗: Five years
Safety parameters will be evaluated at each study visit and recorded as adverse events.
Efficacy measured as change in C-peptide Area under the curve to a mixed mealtolerance test.
时间窗: One year
Change in C-peptide Area under the curve (AUC) (0-120 min) for mixed meal tolerance test (MMTT) at 12 months following Protrans/Placebo infusion when compared to test performed before the start of treatment (baseline).
次要结局
- Insulin independency(One year)
- Time in target(12 months)
- Time in range(12 months)
- C-peptide(6 months)
- Low insulin needs(12 months)
- HbA1c(12 months)
- Change in peak C-peptide(12 months)
- Insulin needs(12 months)
- Low insulin needs(6 months)
- Insulin needs(6 months)
- HbA1c(6 months)
- Time in target(6 months)
- Time in range(6 months)
- Change in peak C-peptide(6 months)
研究者
Per-Ola Carlsson
Professor, Senior consultant in Endocrinology and Diabetology
Uppsala University Hospital