A Multicenter, Randomized, Partial-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 76
- 试验地点
- 72
- 主要终点
- Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
研究概览
简要总结
This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed enrollment will be opened to the child cohort. The purpose of this study is to evaluate the safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
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
- 6 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of T1DM according to the ADA criteria.
- •Current use of injected insulin therapy and one positive result on testing for any of the following antibodies (If not currently on insulin therapy, must have positive result for at least two of the below antibodies):
- •Anti-islet-cell antibodies (islet cell antigen 512, insulinoma associated protein 2),
- •Anti-glutamic acid decarboxylase antibodies, or
- •Anti-insulin antibodies (unless received insulin therapy for > 7 days).
- •Body Mass Index (BMI) ≤ 28 kg/m2 for adults (≥ 20 years of age) OR ≤ 90th percentile in accordance with the Centers for Disease Control BMI assessment for children and teens (2 through 19 years old).
排除标准
- •History of or current diabetic retinopathy, neuropathy, or nephropathy.
- •Known thrombophilia or history of thrombosis.
- •Malignant disease (including malignant melanoma; however, other forms of skin cancer are allowed) within five years of randomization.
- •Active Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, or Human Immunodeficiency Virus infection.
- •History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s).
- •Known selective or severe Immunoglobulin A deficiency.
- •Elevated liver enzymes (aspartate transaminase, alanine aminotransferase, and alkaline phosphatase) equal to or greater than 2.5 times the upper limit of normal.
- •Therapy with exenatide or any other agents that stimulate pancreatic β cell regeneration or insulin secretion, or any antidiabetic agents (oral or parenteral) other than insulin within one month prior to screening.
- •Use of omega-3 fatty acid supplements, including fish oil, within seven days prior to screening.
- •Current or planned therapy with inhaled insulin, if it becomes available.
- •Chronic use of systemic steroids, with the exception of inhaled steroids, above a stable dose equivalent to 5 mg/day prednisone (e.g., 10 mg every 2 days) within 4 weeks prior to randomization. It is recommended to maintain the same dose throughout the study. (Note: Subjects with autoimmune conditions (i.e., asthma) necessitating treatment with systemic short-term corticosteroids and administered a rapid taper are eligible per protocol with the caveat that the tapering is complete or decreased to the minimum requirement (i.e., 5 mg/day) at least 1 week prior to the Baseline visit (when randomization occurs) to ensure the subject is stable. For longer term steroid usage, please consult the Grifols Medical Monitor before considering the subject for study participation.)
- •Treatment with immunosuppressants or cytostatic agents within 6 months of randomization.
研究组 & 干预措施
Alpha1-PI 180 mg/kg/wk, 26 weeks
180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
干预措施: 180 mg/kg Alpha1-PI (Biological)
90 mg/kg/wk Alpha1-PI, 26 weeks
90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
干预措施: 90 mg/kg Alpha1-PI (Biological)
Placebo, 26 weeks
Weekly infusions of placebo for 26 weeks.
干预措施: Placebo (Biological)
180 mg/kg/wk Alpha1-PI, 13 weeks
180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.
干预措施: 180 mg/kg Alpha1-PI (Biological)
90 mg/kg/wk Alpha1-PI, 13 weeks
90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
干预措施: 90 mg/kg Alpha1-PI (Biological)
Placebo, 13 weeks
Weekly infusions of placebo for 13 weeks.
干预措施: Placebo (Biological)
结局指标
主要结局
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
时间窗: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.
次要结局
- Change From Baseline for MMTT Stimulated C-peptide 2h AUC(Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink))
- Change From Baseline for HbA1c Levels(Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104)
- Number of Subjects With Overall Severe Hypoglycemic Episodes(104 weeks)
- Change From Baseline for Mean Daily Insulin Dose Requirements(Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104)
- Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime(Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104)