NCT01724931已完成2 期
A Phase 2 Double-Blind, Placebo-Controlled, Randomized Dose Finding Study For The Efficacy And Safety Of Aminopterin In Methotrexate-Naive Rheumatoid Arthritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 15
- 主要终点
- ACR20
研究概览
简要总结
The purpose of this study is to determine whether aminopterin is effective in the treatment of rheumatoid arthritis (RA).
详细描述
This is a double-blind, randomized, placebo-controlled, dose ranging study that will evaluate the safety, efficacy, and pharmacokinetic properties (the absorption, distribution and excretion) of aminopterin following oral administration by subjects with active rheumatoid arthritis (≥ 6 tender and ≥ 6 swollen joints) who have not been treated with methotrexate (MTX). Subjects are randomized to one of three treatments: placebo, 1 mg of LD-aminopterin, or 3 mg of LD-aminopterin in a 1:1:1 ratio. The study hypothesis is that the 3 mg LD-aminopterin per week is effective at treating rheumatoid arthritis compared to 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
- 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
- •> 18 years of age.
- •A diagnosis of RA established by the ACR/EULAR 2010 criteria applied to patients who: 1) have >1 joint with definite clinical synovitis (swelling); 2) with the synovitis not better explained by another disease.
- •Add scores of categories A-D; a score >6/10 is required for study entry.
- •A. Joint involvement:
- •1 large joint=0; 2-10 large joints=1; 1-3 small joints (with or without involvement of large joints=2; 4-10 small joints (with or without involvement of large joints)=3; >10 joints (at least 1 small joint)=
- •B. Serology (at least 1 test result is needed for classification):
- •Negative RF and negative ACPA=0; Low-positive RF or low-positive ACPA=2; High-positive RF or high-positive ACPA=
- •C. Acute-phase reactants (at least 1 test result is needed for classification):
- •Normal CRP and normal ESR=0; Abnormal CRP or abnormal ESR=
- •D. Duration of symptoms:
- •less than 6 weeks=0; 6 weeks or greater=
- •Class I, II or III functional according to the ACR 1992 revised criteria for the classification of global functional status in RA.
- •RA is active, defined as ≥ 6 swollen joints and ≥ 6 tender joints.
- •Ability to understand and sign written informed consent.
- •For sexually active men and for women of childbearing potential, an adequate form of contraception.
- •For pre-menopausal women, a negative pregnancy test, obtained within 1 week prior to first study drug dose.
- •Negative serology for hepatitis B and hepatitis C.
- •The following screening laboratory blood tests must have the following values, or not clinically significant as determined by the PI and Medical Monitor: WBC WNL; absolute neutrophil count > lower limit of normal; platelet count WNL; hemoglobin >10.0 g/dL; AST WNL.
- •Adequate renal function: GFR estimated by Cockcroft-Gault formula >60 ml/min
排除标准
- •Known history of hepatitis, HIV infection, interstitial lung disease.
- •Alcohol consumption on a regular basis and unwilling, or unable, to discontinue this consumption during the study period.
- •Prior methotrexate or aminopterin therapy.
- •Prior biologic drug therapy (e.g., etanercept, adalimumab, infliximab).
- •Within 2 weeks prior to Study Day 0, or on Study Day 0, or at any time during the study, use of any of the following medications that may result in drug/drug interactions with AMT: trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; triamethamine; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin).
- •At Study Day 0 use of DMARDs and biologics (except antimalarials) including oral or injectable gold, azathioprine, penicillamine, sulfasalazine or cyclosporine. Subjects previously treated with any of these medications are eligible provided a 28 day wash-out is completed prior to Study Day
- •Antimalarial can be continued at the same dose if they have been administered at the same dose for 8 weeks before Study Day 0, and they will be administered at the same dose throughout the study. NSAIDs or corticosteroid (≤ 10 mg prednisone or equivalent/day) may be continued at the same dose if they have been used at a stable dose for two weeks prior to Study Day 0, and will be continued at the same doses throughout the study.
- •Use of corticosteroids in excess of 10 mg prednisone or equivalent/day.
- •Known concurrent malignancy except basal or squamous cell skin carcinoma, or cervical carcinoma in situ.
- •Concurrent participation in another clinical trial involving experimental treatment within 30 days of Study Day
- •Current and uncontrolled infection, cardiovascular, renal, pulmonary, hepatic or GI conditions that will interfere with the conduct of the trial or pose a morbid risk.
- •Investigator's opinion that a concurrent disease or condition impairs the subject's ability to complete the trial: includes psychological, familial, sociological, geographical or medical conditions.
研究组 & 干预措施
Placebo
Placebo Comparator
Placebo once weekly
干预措施: placebo (Drug)
3 mg LD-Aminopterin
Experimental
3 mg LD-aminopterin once weekly
干预措施: LD-aminopterin (Drug)
1 mg LD-aminopterin
Experimental
1 mg LD-aminopterin once weekly
干预措施: LD-aminopterin (Drug)
结局指标
主要结局
ACR20
时间窗: Study Day 84
The primary efficacy endpoint, determined at study day 84 or last observation carried forward (LOCF), is the percent of subjects who obtain ACR20 in the 3 mg/week LD-AMT dose compared to placebo.
次要结局
- ACR20(Study Day 84)
研究者
研究点 (15)
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