A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-articular Dose of the TrkA Inhibitor, GZ389988, in Patients With Painful Osteoarthritis of the Knee
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 104
- 试验地点
- 2
- 主要终点
- Change from baseline in weekly mean score of Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 pain subscore (walking pain) collected daily in the target knee, as measured by the Visual Analogue Scale (VAS) 0-100
研究概览
简要总结
Primary Objective:
To assess the efficacy of a single intraarticular dose of GZ389988 compared to placebo for relief of knee pain in patients with osteoarthritis (OA) of the knee.
Secondary Objectives:
To assess the safety and tolerability of a single intraarticular dose of GZ389988 in patients with painful OA of the knee.
To assess the pharmacokinetic parameters of a single intraarticular dose of GZ389988 in patients with painful OA of the knee.
详细描述
Screening will be performed within 21 days of dosing. Following the single dose of study medication, the study period for each patient will be 84 ± 7 days up to the end-of-study visit.
Total duration for one patient will be up to 16 weeks (up to the end-of-study visit), not including the long-term observational safety follow-up phone call for 12 additional weeks.
The collection of primary endpoint data up to Week 4 for futility analysis is optional. Assuming a possible step-down in dose due to safety/tolerability reasons, the total expected maximum number of included patients could be increased up to a maximum of 182 patients.
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
- 40 Years 至 80 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
GZ389988
Single intraarticular injection of GZ389988 in the knee joint
干预措施: GZ389988 (Drug)
GZ389988
Single intraarticular injection of GZ389988 in the knee joint
干预措施: acetaminophen or paracetamol (Drug)
GZ389988
Single intraarticular injection of GZ389988 in the knee joint
干预措施: fixed combination of paracetamol + codeine (Drug)
GZ389988
Single intraarticular injection of GZ389988 in the knee joint
干预措施: fixed combination of paracetamol + tramadol hydrochloride (Drug)
Placebo
Single intraarticular injection of placebo for GZ389988 in the knee joint
干预措施: placebo (Drug)
Placebo
Single intraarticular injection of placebo for GZ389988 in the knee joint
干预措施: acetaminophen or paracetamol (Drug)
Placebo
Single intraarticular injection of placebo for GZ389988 in the knee joint
干预措施: fixed combination of paracetamol + codeine (Drug)
Placebo
Single intraarticular injection of placebo for GZ389988 in the knee joint
干预措施: fixed combination of paracetamol + tramadol hydrochloride (Drug)
结局指标
主要结局
Change from baseline in weekly mean score of Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 pain subscore (walking pain) collected daily in the target knee, as measured by the Visual Analogue Scale (VAS) 0-100
时间窗: Averaged over 4 weeks (up to Day 28)
次要结局
- Change from baseline in weekly mean score of WOMAC A1 pain sub-score (walking pain) collected daily in the target knee, as measured by the VAS 0-100(Averaged over 12 weeks (up to Day 84))
- Change from baseline in weekly mean score of WOMAC A1 pain sub-score collected daily in the target knee(At 1, 2, 3, 4, 6, 8, 10, and 12 weeks)
- Change from baseline in weekly mean score of overall knee pain collected daily in the target knee(At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks)
- Change from baseline in Patient Global Assessment (PGA) of disease status(At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks)
- Change from baseline in WOMAC index (total score for pain, stiffness, and physical function subscales), pain, stiffness and physical function sub-scores(Averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks)
- Patient Global Impression of Change (PGIC)(Over the last 4 weeks at Day 28 (1 to 4 weeks), Day 56 (5 to 8 weeks), and Day 84 (9 to 12 weeks))
- Patient Global Assessment of Response to Therapy (PGART)(Over the last 4 weeks at Day 28 (1 to 4 weeks), Day 56 (5 to 8 weeks), and Day 84 (9 to 12 weeks))
- Rate of response to therapy according to Outcome Measures in Rheumatology committee (OMERACT) and the Osteoarthritis Research Society International (OARSI)(By Day 28, Day 56, and Day 84)
- WOMAC A1 responder rate based on percentage of patients with reduction in pain intensity of at least 30% and 50% at endpoint compared to baseline(Over 4 weeks (up to Day 28) and 12 weeks (up to Day 84) and at 1, 2, 3, 4, 6, 8, 10, and 12 weeks)
- Time to first WOMAC A1 response for ≥30% reduction in pain intensity(At 1, 2, 3, 4, 6, 8, 10, 12 weeks)
- Time to first WOMAC A1 response for 50% reduction in pain intensity(At 1, 2, 3, 4, 6, 8, 10, 12 weeks)
- Amount of rescue medication intake(Up to Day 84)