A Phase 2a, Open Label, Multiple-Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Teplizumab in Adults With Moderate or More Severe Psoriasis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- MacroGenics
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Adverse Events (AE)
研究概览
简要总结
The purpose of this study is to determine whether teplizumab is safe when administered subcutaneously (by needle under the skin) in subjects with psoriasis. The study will also evaluate how long teplizumab stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it improves psoriasis.
详细描述
This study will test the hypotheses that therapeutic modulation of T-cell function by teplizumab is well tolerated in subjects with moderate or more severe psoriasis, and that this treatment ameliorates the immunopathology of psoriasis. This study will evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) administration for 6 days. Once the SC maximum tolerated dose is identified, this dose will be administered to a cohort of subject by intravenous for comparison of PK and PD.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic plaque psoriasis that has been present for more than 6 months and involves at least 10% Body Surface Area (BSA).
- •Baseline LS-PGA score of moderate or greater severity.
- •Weight <= 125 kg (276 lb) and a BSA <= 2.5 m^2.
排除标准
- •Clinically significant flare of psoriasis during the 12 weeks before enrollment.
- •Guttate, erythrodermic, palmoplantar, or pustular (von Zumbusch) psoriasis
- •Orally administered systemic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks before enrollment.
- •Prior administration of a biologic agent/monoclonal antibody within 12 weeks before enrollment or 5 half-lives of the agent, whichever is greater.
- •Prior otelixizumab, OKT®3, or teplizumab.
- •Treatment within the last 30 days with a non-biologic drug or device that has not received regulatory approval for any indication at the time of study entry or are unwilling to forgo experimental treatment other than teplizumab during this study.
- •Treatment with live vaccine within 8 weeks before enrollment or during study; vaccination with an antigen or killed organism during the study, within 8 weeks before enrollment, or 8 weeks after dosing.
- •Evidence of active infection.
- •Positive IgM test for hepatitis A.
- •History of or positive test for hepatitis B, C, or D.
- •History of or positive test for HIV.
- •Are immunocompromised, have had recent or current serious systemic or local infection, clinical or radiological evidence of active tuberculosis, or evidence of latent TB infection.
- •History of chronic liver disease, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or epilepsy.
- •Current serious or unstable illnesses or allergies.
- •Clinically significant laboratory abnormalities.
- •Presence of serological reactivity to teplizumab (in subjects previously treated with therapeutic antibodies).
- •Clinically significant ECG abnormalities.
研究组 & 干预措施
teplizumab
Anti CD-3 monoclonal antibody
干预措施: teplizumab (Biological)
结局指标
主要结局
Adverse Events (AE)
时间窗: Day 0 through Day 84
Primary endpoints include safety data such as vital signs, physical examinations, electrocardiograms, AE reports, and laboratory test results.
次要结局
- Number of Participants Improved on Lattice System Physician's Global Assessment (LS-PGA)(Day 0, 14, 28, 63 and 84)
- Number of Participants Improved on the Psoriasis Area and Severity Index (PASI)(Day 0, 14, 28, 63 and 84)
- Physician's Global Assessment (PGA)(Day 0, 14, 28, 63 and 84)
- Teplizumab Blood Levels(Day 0 through Day 84)