A Randomized, Four-arm, Canakinumab Placebo-controlled, Participant, Investigator and Sponsor-blinded Study Investigating the Safety, Tolerability and Efficacy of Intra-articular Canakinumab Followed by Intra-articular LNA043 in Patients With Knee Osteoarthritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 6
- 主要终点
- Change in Cartilage Volume in the Index Region Measured by MRI at Day 197 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)
研究概览
简要总结
The study was established to show safety and efficacy of canakinumab and LNA043 in patients with knee osteoarthritis (OA).
详细描述
This was a non-confirmatory, randomized, four arm, placebo-controlled, participant-, investigator and sponsor-blinded study in participants with symptomatic knee OA with synovial inflammation.
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)
盲法说明
Masking only applies to the canakinumab treatment. LNA043 treatment is open label.
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
- •Moderate to severe OA pain (corresponding to NRS Pain ≥5 to ≤9) in the target knee for the majority of days in the last 3 months prior to Screening
- •KOOS pain subscale <60 for the target knee during Screening
- •High sensitivity C-reactive Protein (hsCRP) ≥1.8 mg/L
- •Radiographic KL grade 2 to 4 knee OA and joint space width (JSW) 2.0-4.0 mm (men) or 1.5-3.5 mm (women) in the medial tibiofemoral compartment (TFC) in the target knee
- •Contrast-enhanced MRI (CE-MRI) diagnosed moderate or severe knee synovitis based on an established synovititis scoring system (moderate score 9-12 or severe score ≥13)
排除标准
- •History of, or planned; knee replacement (partial or total) in either knee; arthroscopy or lavage in either knee within 6 months prior to screening; any other previous surgical intervention in the target knee, or for the contralateral knee within 12 months prior to Screening, including mosaicplasty, microfracture, meniscectomy >50% or osteotomy
- •Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to screening
- •Malalignment >7.5° in the target knee (either varus or valgus)
- •Any diagnosis of systemic inflammatory arthritis or connective tissue disease, including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, Paget's disease, systemic lupus erythematosus) or other systemic condition that might confound assessment of OA (e.g. fibromyalgia)
- •Ipsilateral hip OA or hip prosthesis recently implanted (within 1 year prior to screening) or hip replacement on either side planned within the study period
研究组 & 干预措施
Placebo+LNA043
Placebo to canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71
干预措施: LNA043 (Biological)
Placebo+LNA043
Placebo to canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71
干预措施: Placebo to canakinumab (Other)
Placebo
Placebo to canakinumab on Day 1
干预措施: Placebo to canakinumab (Other)
canakinumab + LNA043
Canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71
干预措施: canakinumab (Biological)
canakinumab + LNA043
Canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71
干预措施: LNA043 (Biological)
canakinumab
Canakinumab on Day 1
干预措施: canakinumab (Biological)
结局指标
主要结局
Change in Cartilage Volume in the Index Region Measured by MRI at Day 197 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)
时间窗: Baseline, Day 197
Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale (ACZ885 Versus Placebo to ACZ885)
时间窗: Baseline, Day 85
The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS pain consisting of 9 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.
次要结局
- Maximum Serum Concentration (Cmax) of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)(Pre-dose Day 1, Day 15, Day 43 and 60 minutes after first injection of LNA043 on Day 15)
- Change in Cartilage Volume of the Index Region Measured by MRI at Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)(Baseline, Day 365)
- Change in Synovitis Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI) (ACZ885 Versus Placebo to ACZ885)(Baseline, Day 85)
- Maximum Serum Concentration (Cmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)(Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15)
- Number of Participants With Anti-LNA043 Antibodies (Placebo to ACZ885+LNA043 Versus ACZ885 + LNA043)(From pre-dose up to Day 365)
- Area Under Serum Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)(Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15)
- Change in Cartilage Volume of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)(Baseline, Day 197 and Day 365)
- Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885)(Baseline, Day 15, 29, 43, 57, 71, 85)
- Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)(Pre-dose on Days 1, 15, 43, and 71)
- Time to Reach Maximum Serum Concentration (Tmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)(Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15)
- Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)(Baseline, Day 197 and 365)
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885)(Baseline, Day 15, 29, 43, 57, 71, 85)
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)(Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365)
- Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)(Baseline, Day 197 and 365)
- Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)(Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365)
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885)(Baseline, Day 15, 29, 43, 57, 71, 85)
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)(Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365)