TRX4 Therapeutic Evaluation of Different Multi-Dose Regimens in Type 1 Diabetes Mellitus (TTEDD)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to optimize several multi-dose regimens of otelixizumab, determine the highest biologically active dose, evaluate biomarkers and surrogates of efficacy, and to evaluate the effects of each multi-dose regimen of otelixizumab against standard safety and efficacy parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults 12 to 45 years old who are in good general health
- •Confirmed diagnosis of insulin requiring type 1 diabetes mellitus with good glycemic control
- •Measurable C-peptide levels
排除标准
- •Females must not be pregnant or lactating and willing to practice contraception
- •No prior malignancy, other than non-melanoma skin cancer
- •Body Mass Index (BMI) > 32 at screening
研究组 & 干预措施
otelixizumab
干预措施: Otelixizumab (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to Month 24
AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Number of Participants With Abnormal Hematology Values of Potential Clinical Concern (PCC)
时间窗: Up to Month 48
Hematology parameters: hemoglobin, white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were assessed for abnormal PCC values. Data for abnormal parameters (high and low) is presented. Only those parameters for which at least one value of PCC was reported are summarized.
Mean Overall Maximum Cytokines Level
时间窗: Up to Week 8
Levels of cytokines: interferon (IFN)-gamma, interleukin (IL)-10, IL-6 and tumor necrosis factor (TNF)-alpha were assessed. One sample was collected at Baseline, on dose Day 1 at 1, 2, 3, and 8 hours post-end of infusion (EOI) and on all other dosing days at pre-dose, and 1, 2, 3, and 8 hour post-EOI. After the completion of dosing, on Day 21 and Week 8, only the IL-10 level was assessed in the cytokine blood sample.
Number of Participants With Cytokine Release AE
时间窗: Up to Month 24
AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Cytokine release AEs were defined as occurring during dosing or within a limited time window after the last dose.
Number of Participants With Abnormal Clinical Chemistry Values of PCC
时间窗: Up to Month 48
Clinical chemistry parameters: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase, lactate dehydrogenase, lipids, blood urea nitrogen, creatinine, uric acid, sodium, potassium, chloride, carbon dioxide, creatinine phosphokinase, albumin, calcium, magnesium, glucose, phosphate, bicarbonate and total protein were assessed for abnormal PCC values. Data for abnormal parameters (high and low) is presented. Only those parameters for which at least one value of PCC was reported are summarized.
Number of Participants With Abnormal Urinalysis Dipstick Results
时间窗: Up to Month 48
Urinalysis parameters: Occult blood, Glucose urine, Ketones, Leukocyte esterase, Nitrite, pH, Protein urine were assessed. Abnormal values for occult blood and ketones were presented as 1+, 2+ and 3+ (the plus sign increases with a higher level of parameters: 1+=slightly positive, 2+=positive, 3+=high positive). Abnormal glucose urine values were presented as 50, 100, 250 and 1000 mg/dL. Abnormal nitrite values were presented as 'positive', and abnormal urine protein values were presented as 30 and 100 mg/dL.
Number of Participants With Positive Epstein Barr Virus (EBV) Viral Load
时间窗: Up to Month 18
EBV load was measured using quantitative polymerase chain reaction (PCR) method. If a participant had an EBV viral load of \>100,000 copies/10\^6 peripheral blood mononuclear cells (c/10\^6 PBMC) lymphocytes at any time post-dose, the test was repeated immediately. Data for participants with abnormal viral load is presented.
次要结局
- Mean CD4+/CD8+ Ratio(Day 8 and 28)
- Amounts of Cell-bound Otelixizumab on CD4+ and CD8+ T Cells(At the screening visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.)
- Saturation of CD4+ and CD8+ T Cells With Otelixizumab(At the screening visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.)
- CD3/TCR Complexes on CD4+ and CD8+ T Cells(At the Screen visit and at Baseline. On dose Day 1, at EOI and 4 hour post-SOI. On all other dosing days, at pre-dose, EOI and 4 hour post-SOI up to 48 months.)
- Maximum Plasma Drug Concentration (Cmax) of Otelixizumab(At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-SOI. On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.)
- Time of Last Quantifiable Drug Concentration (Tlast) and Time of Occurrence of Maximum Plasma Drug Concentration (Tmax) of Otelixizumab(At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-SOI. On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.)
- Mean Lymphocytes Subsets (CD19+ B Cells, CD4+CD25hiFoxP3+ T Cells, CD8+CD25+FoxP3+ T Cells) Count(Day 8 and 28)
- Mean Lymphocytes Subsets (CD4+ T Cells, CD8+ T Cells) Count(Day 8 and 28)
- Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUClast) of Otelixizumab(At Baseline, and on all dose days except the final dose day, at pre-dose, EOI, and 4 hour post-start of infusion (SOI). On Dose Day 5, at pre-dose, EOI, and 3.5, 4, 5, and 8-10 hour post-SOI.)
- Change From Baseline in Percent Glycosylated Hemoglobin (HbA1c)(Baseline and up to Month 48)
- Percent Lymphocytes Subsets (CD25+CD8+Tregs) Count(Day 8 and 28)
- Number of Participants With Detectable Anti-otelixizumab Antiglobulin Response(Up to Month 48)
- Number of Participants With Use of Analgesics, Antihistamines and IV Hydration as Concomitant Medication During Dosing Days(Up to Day 8)