A Prospective, Multi-center, Phase 1b/2a Study to Assess the Safety and Tolerability of Different Doses of AG019 Administered Alone or in Association With Teplizumab in Patients With Clinical Recent-onset Type 1 Diabetes Mellitus (T1D)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 18
- 主要终点
- Incidence of Treatment-emergent Adverse Events (TEAE)
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of different doses of AG019 administered alone or in combination with teplizumab in participants with recent-onset type 1 diabetes (T1D).
详细描述
This Phase 1b/2a, multi-center study will be conducted in participants with clinical recent-onset type 1 diabetes (T1D).
The primary objective of this study is to assess the safety and tolerability of different doses of AG019 alone as well as AG019 in combination with teplizumab. The secondary objectives of this study are: to obtain pharmacodynamic (PD) data of AG019 alone as well as AG019 in combination with teplizumab; and to determine the potential presence of AG019 in systemic circulation (safety - systemic exposure) and the presence of L. lactis bacteria in fecal excretion (local exposure): Pharmacokinetic (PK) profile.
This study consists of 2 phases:
Phase 1b: this open-label part of the study will investigate the safety and tolerability of 2 different doses of AG019 in 2 age groups (18-40 years of age and 12-17 years of age).
Phase 2a: this randomized, double-blind part of the study will investigate the safety and tolerability of AG019, in combination with teplizumab, in 2 age groups (18-40 years of age and 12-17 years of age).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
For the randomized participants in the combination cohorts, blinding will be accomplished by arranging for AG019 and placebo components as well as teplizumab and placebo components to have identical packaging.
入排标准
- 年龄范围
- 12 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-lactating females, 18 - 40 years of age (both inclusive) or 12-17 years of age (both inclusive)
- •Diagnosis of diabetes according to the American Diabetes Association (ADA) recommended criteria
- •Evidence of auto-antibodies to at least 1 β-cell autoantigen
- •Stimulated C-peptide measured during 4h Mixed Meal tolerance Test (MMTT) > 0.2 nmol/L
- •The first administration of AG019 should occur no later than 150 days post diagnosis of diabetes
- •Body weight ≥ 33kg
- •Written informed consent obtained and documented (participant, parent, guardian as applicable)
排除标准
- •Previous history of serious cytokine release syndrome to teplizumab or other humanized anti-CD3 monoclonal antibodies with no or minimal capacity to bind Fc receptors. (Participants enrolled in the second phase of the trial in either Combination Cohort 1 or Combination Cohort 2, only)
- •Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomization
- •Participation in another investigational drug trial within 12 weeks prior to the first study drug intake and during participation in this study
- •History of recurrent infections, other autoimmune diseases, cardiac disease, malignancy, or any other (chronic) medical condition which, in the investigator's opinion, could compromise participant safety
- •Documented history of human immunodeficiency virus (HIV), Hepatitis Virus Type C (HCV), Hepatitis Virus Type B (HBV) infection
- •Evidence of active infection with Epstein-Barr Virus (EBV) or cytomegalovirus (CMV)
- •Evidence of active or latent tuberculosis (TB)
- •Administration of anti-CD3 antibody in past year
- •Current therapy with any other anti-diabetic agents other than insulin (MDI, CSII or analogue). Current or planned therapy with experimental (i.e., unapproved) insulin. Patients on therapy for type 2 diabetes (e.g. metformin) should stop their therapy in order to be eligible for study participation.
- •Use of medications known to influence glucose tolerance
- •Daily use of non-steroidal anti-inflammatory agents
- •Compromised GI mucosal integrity or motility, not attributable to T1D (i.e., recent diarrhea, gluten sensitive enteropathy, inflammatory bowel disease, irritable bowel syndrome), or current use of medications known to influence GI motility
- •Positive result of SARS-Cov2 PCR test at screening or within 3 days before randomization
研究组 & 干预措施
AG019 Cohort 1 - Low Dose/Adults
干预措施: AG019 - Low Dose (Biological)
AG019 Cohort 2 - High Dose/Adults
干预措施: AG019 - High Dose (Biological)
AG019 Cohort 3 - Low Dose/Adolescents
干预措施: AG019 - Low Dose (Biological)
AG019 Cohort 4 - High Dose/Adolescents
干预措施: AG019 - High Dose (Biological)
Combination Cohort 1 - Adults
干预措施: Teplizumab (Drug)
Combination Cohort 1 - Adults
干预措施: Placebo-AG019 (Drug)
Combination Cohort 1 - Adults
干预措施: Placebo-Teplizumab (Drug)
Combination Cohort 1 - Adults
干预措施: AG019 - High Dose (Biological)
Combination Cohort 2 - Adolescents
干预措施: Teplizumab (Drug)
Combination Cohort 2 - Adolescents
干预措施: Placebo-AG019 (Drug)
Combination Cohort 2 - Adolescents
干预措施: Placebo-Teplizumab (Drug)
Combination Cohort 2 - Adolescents
干预措施: AG019 - High Dose (Biological)
结局指标
主要结局
Incidence of Treatment-emergent Adverse Events (TEAE)
时间窗: up to 6 months
Treatment-emergent adverse events assessed by the investigator, review of lab reports and information provided by the participant during site visits and/or participant diary with AG019 alone or with teplizumab
次要结局
- AG019 in Systemic Circulation(Up to 3 months after initiation of the treatment)
- L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation(Up to 3 months after initiation of the treatment)
- AG019 in Feces(Up to 8 days after completion of the treatment)
- C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months(up to 12 months)