Intra-articular Treatment With MEN16132 in Patients With Symptomatic Primary Osteoarthritis of the Knee: A Randomized, Multi-centre, Double Blind, Placebo Controlled, Five Parallel Group, Dose Finding Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 423
- 试验地点
- 23
- 主要终点
- WOMAC VA 3.1 A Score (Total Pain)
研究概览
简要总结
The purpose of this study is to determine whether intra-articular (knee joint) administration of MEN16132 is effective reducing the pain from knee osteoarthritis.
详细描述
MEN16132 is a non-peptide bradykinin B2-receptor antagonist showing analgesic and anti-inflammatory activity in nonclinical osteoarthritis models. This study is being conducted as a dose finding study to determine the safety and efficacy of MEN16132, given as three doses/four treatment regimens in comparison to placebo, as well the time to onset and duration of effect.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients ≥40 years old.
- •Symptomatic primary knee osteoarthritis (ACR criteria) since ≥6 months prior to screening, Kellgren Lawrence Grade 2 or 3, and representing an indication for intra-articular drug injection.
- •>50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface).
- •>125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain).
- •Pain in the index knee on at least 50% of the days in the month preceding the screening.
排除标准
- •Patients with Kellgren & Lawrence Grade I or IV (doubtful or severe) osteoarthritis of the knee.
- •Knee condition representing an indication for surgery
- •Patients with Inflammatory or crystal arthropathies, acute fractures, severe loss of bone density, bone necrosis.
- •Patients with isolated patella-femoral syndrome or chondromalacia.
- •Patients with OA predominant in the lateral compartment or any significant valgus deformity.
- •Patients with any other disease or condition interfering with the free use and evaluation of the index knee for the 3 month duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis).
- •Major injury or surgery to the index knee within the previous 12 months prior to screening.
- •Severe hip osteoarthritis ipsilateral to index knee.
- •Any pain >30 mm VAS that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee).
- •Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation or likely to be changed during the duration of the study
- •Use of systemic or topical corticosteroids >10 mg prednisolone equivalent per day during 30 days prior to randomisation.
- •Use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) during 1 or 2 weeks prior to randomisation.
- •Any intra-articular or local periarticular punction, injection or surgery to the index knee during the 6 months prior to screening.
研究组 & 干预措施
Double dose MEN16132 0.125 mg
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
干预措施: MEN16132 - 0.125 mg (Drug)
Double dose MEN16132 0.25 mg
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
干预措施: MEN16132 - 0.25 mg (Drug)
Double dose MEN16132 0.5 mg
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
干预措施: MEN16132 - 0.5 mg (Drug)
Single dose MEN16132 0.5 mg
Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval.
干预措施: MEN16132 - 0.5 mg (Drug)
Placebo
Intra-articular administration of two doses of Placebo at 2-week interval.
干预措施: Placebo (Drug)
结局指标
主要结局
WOMAC VA 3.1 A Score (Total Pain)
时间窗: over the 3 weeks after the first administration
Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The WOMAC VA 3.1 A score (total pain , range 0-500 mm) is the sum of VAS scores (0-100 mm) attributed by the patient to each of the 5 questions referring to osteoarthritic pain experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 A score, the higher is the intensity of pain symptoms (0 = no pain ; 500 = extreme pain). A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. The change from baseline was assessed along 3 weeks after first drug administrations.
次要结局
- WOMAC VA 3.1.B Score (Knee Stiffness)(up to 3 months after first dose)
- WOMAC VA 3.1. C Score (Function)(up to 3 months after first dose)
- Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria(up to 3 months after first dose)
- Patient Global Assessment(up to 3 months after first dose)
- WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25](over the 3 weeks after the first administration)
- WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25](over the 3 weeks after the first administration)
- Adverse Event Reports(up to 4 months after screening)
- Clinically Significant Abnormal Laboratory Tests(up to 4 months from screening)