A Phase Ib Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation, Safety and Tolerability Study of PRTX-100 in Combination With Methotrexate or Leflunomide in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 2
- 主要终点
- Vital Signs and Physical Examinations
研究概览
简要总结
The purpose of this study is to determine the safety and tolerability of PRTX-100 when various doses are given 5 times at weekly intervals to patients with active rheumatoid arthritis that are taking methotrexate or leflunomide. The drug is administered in a physician's office via an intravenous infusion. PRTX-100 may be effective in rheumatoid arthritis by suppressing the immune responses.
PRTX-100 is a highly-purified bacterial protein called Staphylococcal Protein A. In this study, cohorts of patients with active RA will receive sequentially higher doses of PRTX-100. There will be an inactive placebo cohort for comparison. Patients who do not attain low RA disease activity, by a commonly used measure, will leave the study at 3 months after their first dose of study drug.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Active RA with disease duration of not less than 6 months
- •Concomitant stable methotrexate or leflunomide therapy
排除标准
- •Diagnosis of any other inflammatory arthritis
- •ACR Functional Classification of IV
- •Significant systemic involvement secondary to RA (except for secondary Sjogren's syndrome)
- •History of clincally significant hypogammaglobulinemia, common variable immunodeficiency, or humeral immunodeficientncy
- •History of active tuberculosis, pro-thrombotic disorder, venous thrombosis requiring anti-coagulation, substance abuse, or serious psychiatric condition
- •History of allergy or hypersensitivity to aspirin or non-steroidal cyclooxygenase inhibitors, Staphylococcal protein A
- •History or presence of malignancy (except for surgically treated basal or squamous cell carcinoma of the skin at least 3 months prior to the start of study medication)
- •Uncontrolled diabetes or Type 1 diabetes
- •Unstable ischemic heart disease
- •Serious active or recurrent infection, hepatic cirrhosis, or other medically unstable condition
- •Systemic autoimmune diseases other than RA (such as systemic lupus erythematosus, scleroderma, inflammatory bowel disease, inflammatory myopathy)
- •Positive for HIV, hepatitis B surface antigen, or hepatitis C antibody
- •Pregnant or nursing females
- •Inadequate hepatic, renal, or hematologic function
- •Receipt of live vaccine within 5 weeks of start of study medication
- •Concomitant administration of other biologic or non-biologic DMARDS, corticosteroids, or anti-CD20 antibodies
研究组 & 干预措施
1.5 mcg/kg
PRTX-100 at 1.5 mcg/kg administered via infusion once per week for 5 weeks
干预措施: PRTX-100 at 1.5 mcg/kg (Drug)
3.0 mcg/kg
PRTX-100 at 3.0 mcg/kg administered via infusion once per week for 5 weeks
干预措施: PRTX-100 at 3.0 mcg/kg (Drug)
6.0 mcg/kg
PRTX-100 at 6.0 mcg/kg administered via infusion once per week for 5 weeks
干预措施: PRTX-100 at 6.0 mcg/kg (Drug)
12.0 mcg/kg
PRTX-100 at 12.0 mcg/kg administered via infusion once per week for 5 weeks
干预措施: PRTX-100 at 12.0 mcg/kg (Drug)
240 mcg
PRTX-100 at 240 mcg/dose administered via infusion once per week for 5 weeks then once every four weeks for 16 weeks thereafter.
干预措施: PRTX-100 at 240 mcg (Drug)
Placebo
Placebo administered via infusion once per week for 5 weeks
干预措施: Placebo (Drug)
420 mcg
PRTX-100 at 420 mcg/dose administered via infusion once per week for 5 weeks then once every four weeks for 16 weeks thereafter.
干预措施: PRTX-100 at 420 mcg (Drug)
结局指标
主要结局
Vital Signs and Physical Examinations
时间窗: Screening up to 25 Weeks
Change from baseline in blood pressure, heart rate, body temperature, and physical examination parameters
ECG
时间窗: Screening, first dose, 5th dose, 9 weeks, and 25 weeks
Change from baseline in heart rate, PR interval, QT/QTc interval and QRS duration
Adverse Events
时间窗: Screening up to 53 Weeks
Number, severity and attribution of relatedness of Adverse Events
Clinical Laboratory Testing
时间窗: Screening up to 25 weeks
Change from baseline in blood chemistry, hematology, and urinalysis values
次要结局
- Immunogenicity(Prior to first dose, and at 4 weeks, 9 weeks, and 25 weeks)
- Disease activity(Screening up to 53 weeks)
- Pharmacokinetics(Prior to first dose up to 72 hours after last dose of PRTX-100)