A Phase 1, Double-blind, Placebo-controlled, Multiple Intravenous, Ascending-Dose Study of CNTO 136 to Evaluate Safety and Pharmacokinetics in Subjects With Cutaneous Lupus Erythematosus and to Evaluate Safety and Pharmacokinetics in a Cohort of Subjects With Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 主要终点
- Physical examinations
研究概览
简要总结
The main purpose of this study was to evaluate the safety and pharmacokinetics (PK, the action of a drug in the body over a period of time) of multiple intravenous (IV) administrations of CNTO 136 in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). The secondary goal of this study was to assess the pharmacodynamics (biochemical and physiological effects of a drug and the mechanisms of action), immune response, and clinical response.
详细描述
In Part A of this study, patients with CLE were randomly assigned (like flipping a coin) to receive multiple IV doses of CNTO 136, a human anti-IL 6 monoclonal antibody (an immune protein that binds to interleukin 6) or placebo (a substance that appears identical to the treatment and has no active ingredients). Patients and study personnel did not know the identity of the administered treatments (double-blind study). Increasing doses were given, based on safety data collected during the initial weeks of treatment. In Part B, which was also double-blind, patients with SLE were randomly assigned to receive multiple IV doses of the highest well-tolerated dose, as determined in Part A, of CNTO 136, or placebo.
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
- Double (Participant, Investigator)
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
- •Diagnosis of cutaneous lupus erythematosus (CLE, including subacute cutaneous lupus erythematosus, discoid lupus erythematosus, or lupus erythematosus tumidus) or systemic lupus erythematosus (SLE)
- •Had a body weight less than or equal to 100 kg
- •Patients in Part A who were taking systemic medications for CLE had to be on a stable dose for 4 weeks before the first study agent infusion
- •Patients in Part B taking systemic medications for SLE had to be on a stable dose for at least 3 months before the first study agent infusion
- •Given informed consent and willing and able to adhere to the study visit schedule and other protocol requirements; agreed to avoid alcohol intake; and took adequate measures to prevent pregnancy
排除标准
- •Significant history of or concurrent medical condition (other than lupus)
- •Use of specific previous or concurrent medications or investigational therapies
- •Known or suspected allergy to the study agent or it constituents, having recently donated blood, or having any significant laboratory test values requiring intervention
- •Patients with SLE in Part B could not have active central nervous system lupus
研究组 & 干预措施
Part A, 1 mg/kg CNTO 136
干预措施: 1 mg/kg CNTO 136 (Drug)
Part A, 4 mg/kg CNTO 136
干预措施: 4 mg/kg CNTO 136 (Drug)
Part A, 10 mg/kg CNTO 136
干预措施: 10 mg/kg CNTO 136 (Drug)
Part B, 10 mg/kg CNTO 136/placebo
干预措施: 10 mg/kg CNTO 136 (Drug)
Part B, 10 mg/kg CNTO 136/placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Physical examinations
时间窗: Up to 26 weeks
Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination
Albumin and total protein
时间窗: Up to 26 weeks
Electrocardiograms (ECGs)
时间窗: Up to 26 weeks
Number of participants with adverse events
时间窗: Up to 26 weeks
Pharmacokinetic profile of CNTO 136
时间窗: Up to 22 weeks
Blood serum concentration over time
Heart rate
时间窗: Up to 26 weeks
Platelets and total white blood cells (WBC)
时间窗: Up to 26 weeks
Gamma-glutamyl-transferase
时间窗: Up to 26 weeks
Inorganic phosphate
时间窗: Up to 26 weeks
Sitting blood pressure
时间窗: Up to 26 weeks
Respiration rate
时间窗: Up to 26 weeks
Hematocrit
时间窗: Up to 26 weeks
Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
时间窗: Up to 26 weeks
Chloride, potassium, and sodium
时间窗: Up to 26 weeks
Bicarbonate
时间窗: Up to 26 weeks
Creatine kinase
时间窗: Up to 26 weeks
Lymphocytes and neutrophils
时间窗: Up to 26 weeks
Oral temperature
时间窗: Up to 26 weeks
Hemoglobin
时间窗: Up to 26 weeks
Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin
时间窗: Up to 26 weeks
Glucose
时间窗: Up to 26 weeks
Fasting Lipid Panel
时间窗: Up to 8 weeks
Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.
次要结局
- Pharmacodynamics evaluations(Up to 22 weeks)
- Immune response(Up to 22 weeks)
- Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)(Up to 22 weeks)
- British Isles Lupus Assessment Group (BILAG) score(Up to 22 weeks)
- SELENA-SLEDAI Flare Composite(Up to 22 weeks)