A Dose-finding, Pharmacokinetic Phase I Study of the Human Monoclonal Antibody-cytokine Fusion Protein F8IL10 (Dekavil) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 5
- 主要终点
- Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage
研究概览
简要总结
Phase I, multicenter, open-label, dose escalation study to test the efficacy and safety of F8IL10 and methotrexate when given as a combination in rheumatoid arthritis patients.
详细描述
The study is designed to explore whether F8IL10 can be safely administered in combination with standard-dose of MTX in patients with active rheumatoid arthritis and to determine the recommended dose of F8IL10 when combined with MTX.
As soon as the MTD/RD is determined, an additional 12 patients will be randomized (6+6) between F8IL10 (RD) and placebo to further investigate the safety and pharmacacodynamics profile of the study treatment.
Methotrexate (MTX) will be administered as concomitant medication in the dose escalation as well as in the randomized part of the study.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
F8IL10 + MTX
Ten cohorts of 3-6 RA patients will be treated at increasing doses per cohort of F8IL10 plus fixed doses of MTX and folic acid.
An additional 12 patients will be randomized (6+6) in a double blind, placebo controlled cohort with F8IL10 given at RD and placebo. In both arms, MTX will be administered as concomitant medication.
In all coohorts a stable dose of folic acid (5 mg) will be administered on Day 2.
干预措施: F8IL10 (Drug)
F8IL10 + MTX
Ten cohorts of 3-6 RA patients will be treated at increasing doses per cohort of F8IL10 plus fixed doses of MTX and folic acid.
An additional 12 patients will be randomized (6+6) in a double blind, placebo controlled cohort with F8IL10 given at RD and placebo. In both arms, MTX will be administered as concomitant medication.
In all coohorts a stable dose of folic acid (5 mg) will be administered on Day 2.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage
时间窗: Up to day 28
To establish the MTD and the RD of F8IL10 when administered in combination with methotrexate
次要结局
- Terminal half-life [t1/2](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Accumulation ratio for Cmin [R min](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Response rate according to EULAR criteria (Good, Moderate and Non-responders) based on DAS28 score(1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up))
- Area under the drug concentration-time curve [AUC(0 - t last)](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Maximum drug concentration [Cmax](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Area under the drug concentration-time curve, extrapolated to infinity [AUC](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Accumulation ratio for Cmax [Rmax](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- ACR 20, ACR 50, ACR 70 response rate(1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up))
- Time to reach maximum drug concentration [Tmax](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Accumulation ratio for AUC [R AUC](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Relative change over time of blood biomarkers(From day -14 up to day 0 (screening); at day 1 of week 1; at day 1 of week 5 /week 9 (EoT); from week 7 up to week 11 (safety follow-up); from week 11 up to week 15 (efficacy follow-up); from week 11-15 up to week 57-61, every 4 weeks (total follow-up))
- Total clearance following the dose administered [CL](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Volume of distribution at steady state [Vss](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Mean residence time [MRT](At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4)
- Human anti-fusion protein antibodies (HAFA) levels(1) at day 1 of week 1; 2) at day 1 of week 4; 3) from week 5 up to week 9 (EoT visit))
- Change from baseline in DAS28(1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up))