Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients
2015年3月27日 更新者：Novartis Pharmaceuticals
A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose
Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as a single dose (intravenous infusion) in patients with active rheumatoid arthritis in combination with a stable dose of methotrexate.
And to compare efficacy on the dose groups.
研究概览
研究类型
介入性
注册 (实际的)
104
阶段
- 阶段2
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Bad Nauheim、德国、61231
- Novartis Investigative Site
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Erlangen、德国、91054
- Novartis Investigative Site
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Muenchen、德国、80336
- Novartis Investigative Site
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Singapore、新加坡、119074
- Novartis Investigative Site
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Singapore、新加坡、529889
- Novartis Investigative Site
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Bruxelles、比利时、1200
- Novartis Investigative Site
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Merksem、比利时、2170
- Novartis Investigative Site
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Alabama
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Anniston、Alabama、美国、36207-5710
- Novartis Investigative Site
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Arizona
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Tucson、Arizona、美国、85724
- Novartis Investigative Site
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Florida
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Largo、Florida、美国、33773
- Novartis Investigative Site
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Ocala、Florida、美国、34471
- Novartis Investigative Site
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Palm Harbor、Florida、美国、34684
- Novartis Investigative Site
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Port Orange、Florida、美国、32127
- Novartis Investigative Site
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Kentucky
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Madisonville、Kentucky、美国、42431
- Novartis Investigative Site
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Missouri
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St. Louis、Missouri、美国、63110
- Novartis Investigative Site
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Nebraska
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Omaha、Nebraska、美国、68131-2197
- Novartis Investigative Site
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Oklahoma
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Oklahoma City、Oklahoma、美国、73103
- Novartis Investigative Site
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Oregon
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Bend、Oregon、美国、97701
- Novartis Investigative Site
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Pennsylvania
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Duncansville、Pennsylvania、美国、16635
- Novartis Investigative Site
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Amsterdam、荷兰、1105 AZ
- Novartis Investigative Site
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Nijmegen、荷兰、6525 GA
- Novartis Investigative Site
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Guadalajara、西班牙、19002
- Novartis Investigative Site
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Galicia
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La Coruna、Galicia、西班牙、15006
- Novartis Investigative Site
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Santiago de Compostela、Galicia、西班牙、15706
- Novartis Investigative Site
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 75年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
- Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
- Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;
Exclusion Criteria:
- Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
- Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
- Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
- History of renal trauma, glomerulonephritis or patient with one kidney.
- Pregnant or breastfeeding women will be excluded.
- A positive tuberculin skin test.
Other protocol-defined inclusion/exclusion criteria may apply.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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实验性的：Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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实验性的：Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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实验性的：Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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安慰剂比较：Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
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Placebo to AIN457
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实验性的：Parts 2 and 3 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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实验性的：Parts 2 and 3 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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实验性的：Parts 2 and 3 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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安慰剂比较：Parts 2 and 3 - Placebo
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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Placebo to AIN457
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实验性的：Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
|
|
实验性的：Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
|
|
安慰剂比较：Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
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Placebo to AIN457
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
大体时间：Day 43
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Clinical response to treatment was assessed according to ACR20 criteria.
A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.
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Day 43
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Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.
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Day 113
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PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
大体时间：Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
大体时间：Day 43
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Clinical response to treatment was assessed according to ACR50 and ACR70 criteria.
A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant
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Day 43
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Disease Activity Score (DAS28) of Parts 2 and 3 Participants
大体时间：Day 43
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The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS).
The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination.
The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded.
The swollen joint count was calculated in the same manner.
For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment.
For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe.
DAS28 scores range from <2.6 (disease remission) to >5.1 (high disease activity).
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Day 43
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2005年12月1日
初级完成 (实际的)
2008年11月1日
研究完成 (实际的)
2008年11月1日
研究注册日期
首次提交
2008年4月29日
首先提交符合 QC 标准的
2008年4月30日
首次发布 (估计)
2008年5月1日
研究记录更新
最后更新发布 (估计)
2015年3月30日
上次提交的符合 QC 标准的更新
2015年3月27日
最后验证
2015年3月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
AIN457的临床试验
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Novartis Pharmaceuticals终止类风湿关节炎美国, 德国, 希腊, 阿根廷, 巴西, 哥伦比亚, 捷克共和国, 多明尼加共和国, 危地马拉, 印度, 意大利, 日本, 大韩民国, 巴拿马, 葡萄牙, 南非
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Novartis Pharmaceuticals完全的类风湿关节炎哥伦比亚, 美国, 比利时, 火鸡, 泰国, 阿根廷, 意大利, 危地马拉, 印度, 日本, 巴拿马, 匈牙利, 英国, 墨西哥, 波多黎各, 加拿大
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Novartis Pharmaceuticals终止狼疮性肾炎中国, 克罗地亚, 捷克语, 俄罗斯联邦, 火鸡, 澳大利亚, 西班牙, 泰国, 阿根廷, 美国, 丹麦, 希腊, 罗马尼亚, 德国, 大韩民国, 印度, 巴西, 日本, 秘鲁, 葡萄牙, 意大利, 台湾, 越南, 挪威, 哥伦比亚, 瑞典, 危地马拉, 法国, 菲律宾, 智利, 斯洛伐克, 墨西哥, 加拿大, 瑞士
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Novartis Pharmaceuticals主动，不招人
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Academisch Medisch Centrum - Universiteit van Amsterdam...Novartis完全的