AT-1501-I206: An Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Transplanted Islet Cells and AT-1501 Immunomodulation in Adults With Brittle Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Efficacy - Insulin independence
研究概览
简要总结
This study will evaluate the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with T1D undergoing an islet cell transplant.
详细描述
This study will evaluate the safety, tolerability and efficacy of transplantation of experimental islet cells as a potential treatment for brittle type 1 diabetes mellitus. It will also assess the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with brittle T1D undergoing an islet cell transplant. This is a single arm open-label study and up to 6 participants will be recruited at a single center in the United States.
The objectives include:
- To assess the safety and tolerability of transplanted islet cells and immunomodulation with AT-1501, in combination (AT+) with rabbit anti-thymoglobulin (ATG), etanercept and mycophenolate mofetil (MMF/EC-MPS) in adults with T1D undergoing islet cell transplant.
- To assess the efficacy of transplanted islet cells and immunomodulation with AT-1501 in adults with brittle T1D undergoing islet cell transplant.
The duration of treatment may vary from participant to participant and could be up to 2 years. Participants may receive up to 2 islet cell transplants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18-65 years of age
- •A diagnosis of T1D ≥5 years with onset of disease at <40 years of age
- •Involvement in appropriate diabetes management in accordance with the standard of care, as directed by an endocrinologist or diabetologist with at least 3 clinical evaluations within the 12 months prior to Screening; using an insulin pump or multiple daily injection (MDI) insulin therapy; and, unable to achieve acceptable metabolic control because of the occurrence of unexplained SHEs
- •At least 3 unexplained SHEs not secondary to a missed meal or dosing error, in the 12 months prior to Screening
- •Glycosylated hemoglobin (HbA1c) level greater than 7% (53 mmol/mol) and less than 9.5% (80 mmol/mol) inclusive
- •Absence of stimulated C peptide (< 0.3 ng/mL) in response to a mixed meal tolerance test (MMTT) measured at 60 and 90 minutes after the start of consumption
- •Impaired awareness of hypoglycemia (IAH) as defined by a Clarke Score [Clarke 1995] of 4 or more at the time of Screening, during the Screening period, and within the last 6 months prior to the transplant
排除标准
- •Any previous solid organ or islet allotransplant
- •Body mass index (BMI) >30 kg/m2
- •Insulin requirement >1.0 unit/kg/day or <15 units/day
结局指标
主要结局
Efficacy - Insulin independence
时间窗: Date of transplant through Day 364 post- final transplant
The proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant
Safety - Adverse Events (AE) and Adverse Events of Special Interest (AEoSI)
时间窗: Accessed from date of transplant through Day 364 post final transplant for approximately 2 years
Incidence of adverse events
次要结局
- Efficacy - Graft failure(Proportion of participants with graft failure at Day 364 post final transplant)
- Efficacy - HbA1c(Date of transplant through Day 364 post-final transplant)
- Efficacy - Durability of insulin independence - long term(2 and 3 years after discontinuation of AT- 1501)
- Efficacy - Durability of insulin independence(Date of transplant through Day 364 post final transplant)