A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 531
- 试验地点
- 32
- 主要终点
- Change in Knee Pain as Assessed by VAS
研究概览
简要总结
A randomized, double-blind, placebo-controlled, multi-center, phase 3 study to determine the efficacy and safety of TG-C in subjects with Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee, Osteoarthritis Research Society International (OARSI) medial joint space narrowing (JSN) Grade 1 or 2 of the knee joint. TG-C is to be administered by a single intra-articular injection to the damaged joint area via ultrasound guidance. Patients will be followed for 24 months for safety and efficacy.
详细描述
This protocol is designed to assess the safety and efficacy of TG-C in treating symptoms of osteoarthritis of the knee and determining disease modifying effects of TG-C. This study is intended for the treatment of patients with K&L Grade 2 and 3 osteoarthritis and OARSI JSN Grade 1 and 2. Assessments will be made on both the symptomatic effects of pain (VAS), function (WOMAC), and Quality of Life (SF-12) as well as the physical effects (JSW, MRI evaluations of whole knee joint organ tissues and structure) and biochemical biomarkers. This is a placebo-controlled study, TG-C will be compared to normal saline as a control. Additionally, this protocol is designed to evaluate the safety of TG-C. Safety will be evaluated by observation of the injection site for irritation or other effects, the incidence and severity of adverse events, and changes in physical examination findings, radiographic criteria, and laboratory tests. Patients will be followed for 24 months for both safety and efficacy with annual cancer surveillance questionnaires through 15 years post dose for subjects who do not enroll in the Long Term Safety study.
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
Double-blind
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
- •Aged 40 or older
- •BMI between 18.5 and 40
- •KL Grade 2 or 3 knee OA
- •OARSI Grade 1 or 2 medial JSN
- •Pain >= 40 on VAS scale
- •Written informed consent
- •Using birth control
排除标准
- •Knee symptoms that result in difficulty or inability to walk
- •Knee effusion >2+
- •Has Grade 3 OARSI JSN
- •Has a score of 0 or >=5 on the cartilage feature of the WORMS at Screening
- •MRI exam indicates fracture or tumor
- •Has a positive result on RCR testing at screening
- •Has taken NSAIDS with 14 days of baseline
- •Has taken steroidal anti-inflammatory or biologic therapy medication within 2 months of baseline
- •Chronic (>21 days) narcotic use
- •Recent history (within 1 year) of drug or alcohol abuse
- •Pregnant or lactating
- •Has received injection to target knee within 2 months prior to study entry
- •History of various disorders of the knee including but not limited to rheumatoid arthritis, psoriatic arthritis, autoimmune disorder, chondrocalcinosis, gout, hemochromatosis, villonodular synovitis, or synovial chondromatosis
- •Severe hip osteoarthritis ipsilateral to the target knee
- •Ongoing infectious disease including but not limited to HIV, HTLV-1, VSV-G, HBV, or HCV.
- •Clinically significant congestive heart failure, hepatic disease, kidney disease, adrenal insufficiency, acromegaly, uncontrolled hyper- or hypothyroidism, or non-specified uncontrolled endocrine disorder.
- •Uncontrolled diabetes based on a HbA1c > 8% at screening.
- •Documented active malignancy within the last 5 years except for basal cell carcinoma, squamous cell carcinoma, and benign pigmented nevi.
研究组 & 干预措施
Active Treatment (TG-C)
TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
干预措施: TG-C (Biological)
Placebo Control (Normal Saline)
Normal saline, single 2 mL intraarticular injection
干预措施: Placebo Control (Biological)
结局指标
主要结局
Change in Knee Pain as Assessed by VAS
时间窗: 12 months
Assessment of change from baseline in target knee pain using the Visual Analog Scale (VAS). The VAS is a method for the assessment of the intensity of pain. The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from "0" or no pain to "100" very severe pain.
Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC)
时间窗: 12 months
Assessment of change from baseline in target knee function using the WOMAC Osteoarthritis Index. The WOMAC is a proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee including pain, stiffness, and physical functioning of the joints. The response to the questions is in the form of a checked box associated with the response; None, Mild, Moderate, Severe and Extreme.
次要结局
- MRI Assessment of Target Knee(12 months)
- PCS of the SF-12 Questionnaire(12 months)
- WOMAC Total Score(24 Months)
- Health Assessment Questionnaire Disability Index(12 months)