临床试验/NCT04590872

NCT04590872进行中（未招募）1 期

A Pilot Study to Evaluate the Safety and Feasibility of Autologous Tolerogenic Dendritic Cells Loaded With Proinsulin Peptide (C19-A3) in Patients With Type 1 Diabetes

City of Hope Medical Center1 个研究点分布在 1 个国家目标入组 6 人开始时间: 2022年6月16日最近更新: 2026年4月22日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 6
试验地点: 1
主要终点: Incidence of adverse events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase I trial investigates the side effects of PIpepTolDC vaccine in treating patients with type 1 diabetes who use insulin and don't have any other diabetes-related health complications. Type 1 diabetes is an autoimmune disease. This means that the immune system, which usually protects against foreign invaders like bacteria and viruses, attacks the body's insulin-producing betacells in the pancreas (autoimmune response). Overtime, the beta cells are destroyed by the immune system. To stay alive, people with type 1 diabetes must use insulin. PIpepTolDC vaccine is a type of immunotherapy (a treatment that uses a person's own immune system) that works like an allergy shot. The vaccine is made using one's own immune cells (dendritic cells) and a beta cell protein. The vaccine may teach the immune system to stop attacking the beta cells, which may help the beta cells recover and make enough insulin to control blood sugar levels. The vaccine may also help reduce future type 1 diabetes related complications.

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 45 Years（Adult）
性别: All
接受健康志愿者: 否

入选标准

•Willingness to undergo leukapheresis
•Willingness to be followed for about 2 years post-prime dose
•For participants who have a personal continuous glucose monitoring device (CGMD): Willingness to wear a second CGMD during mandated study CGMD visits
•Diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria
•Historical presence of at least one type-1 diabetes associated autoantibody
•GAD specific autoantibodies (glutamic acid decarboxylase autoantibodies [GADA])
•Islet cell cytoplasmic autoantibodies (ICA)
•Islet-antigen 2 specific autoantibody (IA-2A)
•Zinc transporter 8 specific autoantibody (ZNT8A); and/or
•Insulin autoantibody (IAA) (must have been obtained within 7 days of initiating exogenous insulin replacement therapy)
•Time from diagnosis to screening mixed meal tolerance test (MMTT) must be >= 1 year but =< 4 years
•Stable glycemic control per participant's physician
•HbA1c =< 7.5% (=< 58 mmol/mol)
•Non-fasting C-peptide > 0.017 nmol/L
•Stimulated peak C-peptide levels > 0.2 nmol/L from a 2-hour screening MMTT
•Positive for *04:01 allele, *04:02 allele and/or *04:04 allele at the human leukocyte antigen (HLA)-DRB1 gene locus
•Does not possess the protective HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype
•Adequate self-assessment of blood glucose values and recording of glucose values, and administered insulin doses as deemed sufficient by the participant's physician
•No diagnosis of type 1 diabetes related microvascular/macrovascular complications (e.g. nephropathy, retinopathy and neuropathy)
•Deemed acceptable for autologous cell collection (i.e. leukapheresis)
•Only for those who are naive to CGMD use: Deemed able to correctly use a CGM device following training session with a certified diabetes educator and manufacturer representative
•Must meet organ function criteria

排除标准

•Other investigational agents, biologics
•Anti-inflammatory therapy
•Exception: Over-the-counter (OTC) anti-inflammatory agents (e.g. ibuprofen, Tylenol) are generally allowed. However, those requiring chronic OTC anti-inflammatory agents and unable to stop during mandated CGMD study visits will be excluded
•Systemic corticosteroids within 28 days prior to leukapheresis
•Systemic immunosuppressive therapy (e.g. cyclosporine-A, cyclophosphamide)
•Monoclonal antibody therapy
•Allergen immunotherapy within 28 days prior to leukapheresis
•Vaccine(s) within 28 days prior to leukapheresis
•Prior allogeneic organ transplant
•Beta-cell stimulants (e.g. sulfonylureas such as glimepiride), glucagon-like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors (exception: Those with acute exposure to these agents during T1D misdiagnosis may be permitted per PI discretion)
•Insulin sensitizers (e.g. metformin, thiazolidinediones) within 2 months of leukapheresis
•History of insulin sensitizer use (e.g. metformin, thiazolidinediones) ≥ 2 months
•Other autoimmune/inflammatory disorders (exceptions: (i) Type 1 diabetes. (ii) Asymptomatic patients with incidental autoantibody titres may be permitted per PI discretion)
•Other autoimmune/inflammatory disorders (exception type 1 diabetes)
•Active infection requiring antibiotics and/or anti-virals
•Known history of HIV, HBV, HCV, HTLV, syphilis
•History of positive purified protein derivative (PPD) skin test
•History of atopy requiring systemic treatment and/or history of severe allergic reactions
•History or current malignancy
•Unstable cardiac disease
•History of vascular disease (e.g. deep vein thrombosis, stroke)
•Clinically significant uncontrolled illness
•Females only: pregnant or breastfeeding

研究组 & 干预措施

Autologous Tolerogenic Dendritic Cell with Proinsulin Peptide (PIpepTolDC)

Experimental

After completion of leukapheresis, patients receive a prime dose of PIpepTolDC intradermally (ID) on Day 0, followed by a boost dose of PIpepTolDC ID on Day 28.

干预措施: Tolerogenic Dendritic Cell Vaccine (Biological)

结局指标

主要结局

Incidence of adverse events

时间窗: Up to 2 years

Toxicity and adverse events (except hypoglycemia and diabetic ketoacidosis \[DKA\]) will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Hypoglycemia events and DKA will be defined per American Diabetes Association (ADA) grading systems.Observed toxicities will be summarized by type, severity (by CTCAE v 5.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.

Apheresis duration

时间窗: up to 2 years

Measured in hours.

Number of successful manufactured products

时间窗: Up to 2 years

Number of manufactured products that meet the required cell dose/day, sterility (e.g. endotoxin and gram staining), and viability compared to the total number of products manufactured.

Number of CD14+ monocytes

时间窗: up to 2 years

Number of CD14+ monocytes collected during apheresis

TolDC recovery after culture

时间窗: up to 2 years

Number of TolDC generated from CD14+ monocytes

次要结局

Change in T cell responsiveness(Baseline up to 2 years of follow up)
Change in glycosylated hemoglobin A1c (HbA1c) levels(Baseline up to 2 years of follow up)
Change in immune phenotype(Baseline up to 2 years of follow up)
Change in exogenous insulin use (units/kg)(Baseline up to 2 years of follow up)
Change in interferon (IFN)-gamma and IL-10 producing CD4+ T cells(Baseline up to 2 years of follow up)
Change in the number of CD8+ autoreactive T cells(Baseline up to 2 years of follow up)
Change in islet autoantibodies(Baseline up to 2 years of follow up)
Change in stimulated C-peptide area under the curve(Baseline up to 2 years of follow up)
Change in blood glucose levels(Baseline up to 2 years of follow up)

研究者

发起方

City of Hope Medical Center

申办方类型

Other

责任方

Sponsor

研究点 (1)

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