A Phase 1 / 2 Double-Blind, Randomized, Placebo Controlled Study of Safety, Tolerability and Potential Efficacy of AVOTRES Cell-Based Therapy (AVT001) in Patients With Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Avotres Inc.
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAE)
研究概览
简要总结
This is a double-blind, randomized , placebo-controlled study to evaluate the safety and tolerability of AVT001, and to assess AVT001 as a potential treatment for type 1 diabetes (T1D). The trial will involve approximately 24 new-onset T1D subjects.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 1 diabetes, within 12 months of first dosing, confirmed by positive lab result for one or more of the following types of autoantibodies:
- •Glutamic acid decarboxylase (GAD65)
- •Insulinoma associated protein 2 (IA-2, also known as ICA-512)
- •Zinc transporter 8 (ZnT8).
- •Age 16 or older and able to provide informed consent/assent.
- •If a participant is female with reproductive potential, willing to avoid pregnancy through the duration of the trial.
- •Signed and dated written informed consent/assent.
排除标准
- •Poorly controlled diabetes despite insulin therapy, who in the opinion of the investigator would not be a good candidate for participation in a clinical trial
- •Screening hemoglobin <10.0 g/dL; leukocytes <3,000/uL; neutrophils <1,500/uL; lymphocytes <800/uL; platelets <100,000/uL
- •Screening Urine Albumin Excretion > 300mg/gmCr
- •Screening eGFR < 60 mL/min/1.73m2
- •Screening ALT or AST > 1.5x upper limit of normal (ULN)
- •Screening bilirubin > 2.0 mg / dL, or > 3.0 mg / dL for participants with Gilbert's Syndrome
- •Current use of immunosuppressive or immunomodulatory therapies, including pharmacologic doses of systemic steroids. However, topical steroidal creams and inhaled steroids without large systemic absorption are allowed.
- •Coincident medical condition likely to require immunosuppressive or immunomodulatory therapies.
- •Coincident medical condition likely to limit short term (5 year) life expectancy (malignancy, symptomatic coronary artery disease, recent stroke)
- •Prior radiation therapy, immunotherapy (within 1 year of screening), or chemotherapy
- •Serologic evidence of current HIV-1 or HIV-2 infection
- •Serologic evidence of hepatitis C infection
- •Serologic evidence of acute or chronic active hepatitis B as measured by Core Ab positive and / or Surface Antibody antigen positive
- •Subjects with other autoimmune conditions (except compensated or treated autoimmune thyroid, celiac, alopecia, or vitiligo diseases)
- •Women who are pregnant (pregnancy testing during screening), breastfeeding, or planning pregnancy during the study period
- •Inadequate venous access to support leukapheresis
- •Any condition that in the opinion of the investigator(s) would preclude the subject from participating in a clinical trial.
- •Abnormal screening ECG that in the opinion of the investigator or sponsor would pose a safety risk.
研究组 & 干预措施
AVT001 (Treatment)
Infusion of AVT001 (treatment)
干预措施: AVT001 (Drug)
Matched placebo
Infusion of AVT001-matched placebo
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAE)
时间窗: At the Primary Analysis (when all the patients have completed their Day 150 visit)
Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose.
Number of Participants and Severity of Local i.v.-Site Reactions,
时间窗: 5 months post first dose
Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported.
Changes From Baseline of Creatinine
时间窗: 5 months post first dose
Safety/tolerability outcomes - creatinine
Changes From Baseline of Aspartate Aminotransferase
时间窗: 5 months post first dose
Safety/tolerability outcomes - Aspartate Aminotransferase
Changes From Baseline of Alanine Aminotransferase
时间窗: 5 months post first dose
Safety/tolerability outcomes - Alanine Aminotransferase
Changes From Baseline of Total Bilirubin
时间窗: 5 months post first dose
Safety/tolerability outcomes - Total Bilirubin
次要结局
- Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay")(5 months post first dose)
- Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT)(5 months post first dose)
- Changes From Baseline in HbA1c(5 months post first dose)