A 28-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 496
- 试验地点
- 76
- 主要终点
- Change From Baseline OA Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12
研究概览
简要总结
This phase 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intraarticularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study will utilize patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.
详细描述
SM04690-OA-10 was a phase 3, 28-week multicenter, randomized, double-blind, placebo-controlled, parallel group study investigating the safety, tolerability and efficacy of lorecivivint 0.07 mg (compared with placebo) injected into the target knee joint of moderately to severely symptomatic knee OA subjects.
Patient-reported outcomes included Pain Numeric Rating Scale (NRS) [0-10], Western Ontario and McMaster Universities Arthritis Index (WOMAC), and Patient Global Assessment (PGA) of knee osteoarthritis.
The primary efficacy endpoint was change from baseline in target knee Pain NRS at Week 12. Secondary endpoints included change at Week 12 in WOMAC Function and PGA.
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, 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
- •Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
- •Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
- •Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at the Screening Visit (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
- •Radiographic disease Stage 2 or 3 in target knee within 24 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
- •Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)
- •Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
- •Primary source of pain throughout the body is due to OA in the target knee
- •Body mass index (BMI) ≤ 35 kg/m2 at the Screening Visit
- •Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, unless any of these drugs are allowed per protocol and prescribed by a physician to treat a specific condition
排除标准
- •Pregnant women, breastfeeding women, and women who are not post-menopausal (defined as 12 months with no menses without an alternative medical cause) or permanently surgically sterile (includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) who have a positive or indeterminate pregnancy test result at the Screening Visit or Day 1
- •Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus > 10°, valgus > 10°) by radiograph within 24 weeks of the Screening Visit as assessed by independent central readers
- •Partial or complete joint replacement in either knee
- •Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
- •Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
- •Intra-articular (IA) injection into the target knee with a therapeutic aim including, but not limited to hyaluronic acid, platelet-rich plasma (PRP), and stem cell therapies within 26 weeks prior to Day 1; or IA glucocorticoids within 12 weeks prior to Day 1 allowed
- •Previous treatment with lorecivivint (SM04690)
- •Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
- •Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial
- •Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1
- •History of malignancy within the last 5 years; not including subjects with prior history of adequately treated in situ cervical cancer or basal or squamous cell skin cancer
- •Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
- •Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of IA infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at Day 1
研究组 & 干预措施
Lorecivivint
Healthcare professional-administered intra-articular injection; performed on Day 1.
干预措施: Lorecivivint (Drug)
Vehicle
Healthcare professional-administered intra-articular injection; performed on Day 1.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline OA Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12
时间窗: Baseline and Week 12
Evaluate change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 12. The pain NRS is an 11-point scale \[0-10\] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain.
次要结局
- Change From Baseline OA Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 24(Baseline and Week 24)
- Change From Baseline OA Function in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12(Baseline and Week 12)
- Change From Baseline OA Function in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 24(Baseline and Week 24)
- Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12(Baseline and Week 12)
- Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 24(Baseline and Week 24)