A Double-blind, Randomised, Placebo-controlled, Four Parallel Arm, Dose-finding Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Single Intra-articular Injections of Fasitibant in Patients With Symptomatic Osteoarthritis of the Knee.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 436
- 试验地点
- 25
- 主要终点
- Change in WOMAC A
研究概览
简要总结
This study is designed as a double-blind, randomised, placebo-controlled, four parallel arm, dose-finding study, to be conducted in approximately 26 sites, to evaluate the efficacy, safety, tolerability, and pharmacokinetics of single intra-articular (IA) injections of fasitibant in patients with symptomatic osteoarthritis (OA) of the knee.
Approximately 400 male and female patients 40-80 years old, with BMI < 30 kg/m² and with a clinical diagnosis of symptomatic primary osteoarthritis of the knee will be randomised to a total of 4 treatment arms. Each arm includes a single intra-articular injection of one of three dosages of fasitibant (low, intermediate and high dose) OR placebo. The randomisation ratio will be 1:1:1:1.
The primary efficacy variable will be the change of the Western Ontario and McMaster Universities Visual Analogue Scale 3.1 A (WOMAC VA 3.1 A) (total pain) subscore from baseline up to 2 weeks after randomisation. Safety will be assessed by monitoring adverse events and clinical laboratory tests; local tolerability at the injection site will also be assessed. In addition, the population pharmacokinetics and the exposure-response relationship will be evaluated.
The individual experimental clinical phase will last up to maximal 15 weeks encompassing 7 planned visits at site, including screening, randomisation, 4 follow-up visits and the End of study visit.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 40 to 80 years with BMI < 30 kg/m²
- •Patient with Kellgren-Lawrence Grade 2 to 3, symptomatic primary osteoarthritis at the index knee (ACR criteria), for which an IA treatment is indicated
- •Pain of moderate to severe intensity, even if treated with chronic doses of non steroidal antinflammatory drugs
排除标准
- •History of hypersensitivity/allergy to drugs including paracetamol and to disinfectants
- •Any pharmacological treatment of concomitant disease(s) started or changed during 4 weeks prior to randomisation, or likely to be changed during the course of the study
- •Use of systemic or topical corticosteroids > 10 mg prednisolone equivalent per day, or immunosuppressant drugs
- •Current use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics, antidepressive agents), including topical treatments
- •Viscosupplementation to the target knee administered < 4 months prior to randomisation and/or scheduled during the course of the study
- •Evidence of clinically significant hepatic disease or of moderate or severe renal insufficiency
- •Current use of any medications that are substrate of CYP3A4 and/or moderate or strong CYP3A4 inhibitors
- •Patients with any clinically relevant or unstable disease, or malignant neoplasms that, in the opinion of the Investigator, may pose the patient at risk, or confound the efficacy and safety results of the study
- •Patients with any clinically relevant abnormal safety laboratory test results, and/or abnormalities in vital signs, and/or ECG parameters
- •Pregnant and breastfeeding women
- •Any sign of significant immunodeficiency, systemic infection, knee infection or knee bursitis
- •Patients with bleeding diathesis or on therapy with anticoagulants
研究组 & 干预措施
Fasitibant low dose
Drug: solution for intra-articular injection
干预措施: Fasitibant- low dose (Drug)
Fasitibant intermediate dose
Drug: solution for intra-articular injection
干预措施: Fasitibant- intermediate dose (Drug)
Fasitibant high dose
Drug: solution for intra-articular injection
干预措施: Fasitibant- high dose (Drug)
PLACEBO
Drug: solution for intra-articular injection
干预措施: Placebo comparator (Drug)
结局指标
主要结局
Change in WOMAC A
时间窗: from baseline up to 2 weeks after randomisation
The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.
次要结局
- Change in WOMAC INDEX(from baseline up to 6 weeks after randomisation)
- Responder Rate According to OMERACT-OARSI Criteria(from baseline up to 6 weeks after randomisation)
- Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate(from baseline up to 6 weeks after randomisation)