A Randomized, Two-arm, Placebo-controlled, Participant and Investigator-blinded Study Investigating the Efficacy, Safety and Tolerability of DFV890 in Patients With Symptomatic Knee Osteoarthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 31
- 主要终点
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale
研究概览
简要总结
This was a double-blinded, two-arm, phase 2a study to assess efficacy, safety and tolerability of DFV890 in participants with symptomatic knee osteoarthritis.
详细描述
The purpose of the Phase 2a proof of concept study was to evaluate the safety and tolerability of DFV890 in participants with symptomatic knee OA, and to determine the efficacy of DFV890 in reducing knee pain as evidenced by change in KOOS (knee injury and osteoarthritis outcome score). The study had a screening period up to 45 days, a treatment period of 12 weeks and a 4-week follow-up period. At most, the study duration was 21 weeks.
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
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants >= 50 and <= 80 years old on the day of Informed Consent signature.
- •Participants must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 35 kg/m2 at screening. BMI = Body weight (kg) / [Height (m)]2
- •High sensitivity C-reactive protein (hsCRP) >=1.8 mg/L at screening
- •Symptomatic OA with pain (corresponding to Numeric Rating Scale [NRS] 5-9, inclusive) in the target knee for the majority of days in the last 3 months prior to screening
- •KOOS pain sub-scale score <= 60 in index knee at screening and baseline
- •Radiographic disease: K&L grade 2 or 3 knee osteoarthritis in the target knee, confirmed by X-ray at screening.
- •Active synovial inflammation at screening (defined a summary score of ≥7 with at least one region scoring 2) on contrast enhanced MRI (CE-MRI) of the whole knee for synovitis detection from 11 sites.
排除标准
- •Total WBC count < 3,000/µL, absolute peripheral blood neutrophil count (ANC) < 1,000/µL, hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/µL at Screening
- •Known autoimmune disease with inflammatory arthritis (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystal-induced arthritis (gout, pseudogout associated arthritis), active acute or chronic infection or past infection of the knee joint, Lyme disease involving the knee, reactive arthritis, systemic cartilage disorders, moderate to severe fibromyalgia (widespread pain index, WPI, >4 out of 19), or a known systemic connective tissue disease
- •Any known active infections, including skin or knee infections or infections that may compromise the immune system, such as HIV or chronic hepatitis B or C infection. COVID-19 specific: PCR or antigen test against COVID-19 is mandatory where required by the local Health Authority and/or by local regulation, e.g. in Germany.
- •Use of prohibited medications: any local i.a. treatment into the knee, including but not restricted to viscosupplementation and corticosteroids within 12 weeks prior to Day 1; long-term treatment (>14 days) with oral corticosteroids >5 mg/day within 4 weeks prior to Day 1; oral glucosamine, chondroitin sulfate, or any nutraceutical with potential activity on cartilage repairfrom screening 1; systemic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), selective Cyclooxygenase-2 (COX- 2) inhibitors or other non-opioid analgesics not defined as basic pain medication within 5 half-lives from PRO assessments; any other immunomodulatory drugs or treatment which cannot be discontinued or switched to a different medication within 28 days or 5 half-lives of screening (whichever is longer if required by local regulations), or until the expected PD effect has returned to baseline.
- •Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to Screening, as per patient judgment.
- •Severe malalignment greater than 7.5 degrees in the target knee (either varus or valgus), measured using x-ray at Screening.
- •Additional protocol-defined inclusion / exclusion criteria may apply.
研究组 & 干预措施
DFV890
DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.
干预措施: DFV890 (Drug)
Placebo
Matching Placebo was administered orally twice per day during 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale
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 pain and 0 indicating extreme pain) 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, baseline-by-timepoints interaction and treatment-by-timepoints interaction as fixed effects. Missing data is assumed to be Missing at Random (MAR).
次要结局
- Change From Baseline in Synovitis Activity Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)(Baseline, Week 12)
- Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Absolute Neutrophil Counts (ANC)(Baseline, Weeks 2, 4, 8 and 12)
- Maximum Plasma Concentration (Cmax) of DFV890(Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h)
- Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of DFV890(Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h)
- Area Under Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of DFV890(Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h)
- Pre-dose Trough Concentration (Ctrough) of DFV890(Week 2 and Week 12: pre-dose)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale(Baseline, Week 2, 4, 8 and 12)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale(Baseline, Week 2, 4, 8 and 12)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale(Baseline, Week 2, 4, 8 and 12)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee-related Quality of Life (QOL) Subscale(Baseline, Week 2, 4, 8 and 12)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale(Baseline, Week 2, 4, 8)
- Change From Baseline in Numeric Rating Scale (NRS) for Pain(Baseline, Weeks 2, 4, 8 and 12)