A Randomized, Two-arm, Placebo-controlled, Participant, Investigator and Sponsor-blinded, Proof-of-concept Study Investigating the Efficacy, Safety and Tolerability of QUC398 in Patients With Symptomatic Knee Osteoarthritis
概览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 101
- 试验地点
- 14
- 主要终点
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale at Week 12
概览
简要总结
The purpose of the study was to find out if the investigational treatment named QUC398 had beneficial effects on osteoarthritis (OA) knee pain and knee cartilage, and if it was safe and tolerated.
详细描述
This was a non-confirmatory study using a randomized, placebo-controlled, parallel-group, participant, investigator and sponsor-blinded design to investigate efficacy, safety and tolerability of subcutaneous injections of QUC398 300 mg vs placebo every 4 weeks (q4w) in participants with symptomatic knee OA.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
participant, investigator and sponsor-blinded
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
- •Weight ≥ 50 kg and body mass index 18 -35 kg/m2 at Screening 1
- •Kellgren-Lawrence grade 2 to 4 in the tibio-femoral compartment in the target knee confirmed by radiography in standing weight-bearing fixed flexion position and posterior-anterior view, at Screening 1
- •mJSN 1-2 in the medial tibiofemoral compartment of the target knee, confirmed with Xray by central reader at Screening 1
- •Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee for the majority of days in the last 3 months prior to Screening 1, as per participant's judgement
- •Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee at Screening 1 and 2
- •Moderate to severe OA pain (corresponding to Pain NRS ≥5 to ≤9) in the target knee during the last 7 days prior to Screening 3, confirmed by:
- •Completed pain diary for at least 6 of the last 7 days prior to Screening 3, AND Diary reported Pain NRS ≥5 to ≤9 for at least 6 of the last 7 days prior to Screening 3
- •\- KOOS pain subscale ≤ 60 in the target knee at Screening 1, Screening 2, and Screening 3
排除标准
- •Painful ipsilateral hip OA defined as a Pain NRS ≥3 on the majority of days in the last 3 months prior to Screening 1, as reported by the patient
- •Symptomatic, patello-femoral pain in the target knee as per investigator's examination at Screening 1
- •Severe malalignment \> 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1
- •Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI
- •Previous exposure to any ADAMTS-5 drug, including QUC
- •History or current diagnosis of ECG abnormalities
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo
Placebo was administered subcutaneous every 4 weeks during 48 weeks.
干预措施: Placebo (Drug)
QUC398 300 mg
QUC398 was administered subcutaneous every 4 weeks during 48 weeks.
干预措施: QUC398 (Drug)
结局指标
主要结局
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale at Week 12
时间窗: Baseline, Week 12
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 pain frequency/severity during functional activities consisting of 9 questions with a recall of 7 days. 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. Change from baseline in KOOS pain score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on a primary estimand framework.
次要结局
- Change From Baseline in Cartilage Volume of the Knee Index Region Measured by 3D-MRI(Baseline, Week 52)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale(Baseline, Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Pain Assessed by a Pain Numerical Rating Scale (NRS)(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Total Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee Related Quality of Life Subscale(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Patient's Global Assessment (PGA) as Assessed by NRS(Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)