A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee, With an Open-Label Safety Extension
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 588
- 试验地点
- 2
- 主要终点
- Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
研究概览
简要总结
This multicenter, randomized, double-blind study will be performed in approximately 600 subjects with chronic idiopathic osteoarthritis (OA) of the knee. An open-label safety extension will follow.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Chronic OA of target knee confirmed by ACR Criteria
- •Pain due to OA in target knee present for at least 6 months:
- •Moderate to severe pain score of 41 mm to 90 mm recorded on a 100 mm VAS immediately following a 50-foot walk
- •A bilateral standing AP X-ray confirming OA of the target knee-obtained within a 6-month period prior to the Screening Visit-and a grade of 2 or 3 according to the Kellgren and Lawrence Grading Scale
- •Ability and willingness to use only acetaminophen as the analgesic (rescue) study medication
- •The acetaminophen dose must not exceed 4 grams/day (4000 mg)
- •If subject has known chronic liver disease, the maximum dose of acetaminophen must not exceed 2 grams/day (2000 mg)
- •The subject must be willing and able to discontinue acetaminophen at least 24 hours prior to all study-specific visits
- •The study specific acetaminophen provided will only be used for knee pain.
- •Ability to perform procedures required of the pain index evaluations (unassisted walking 50 feet on a flat surface and going up and down stairs).
- •Willingness and ability to complete efficacy and safety questionnaires and ability to read and understand study instructions
- •Signed study-specific Subject Informed Consent Form
排除标准
- •Any major injury (including sports injuries) to the target knee within the 12 months prior to the Screening Visit
- •Any surgery to the target knee within the 12 months prior to the Screening Visit, or surgery to the contralateral knee or other weight-bearing joint if it will interfere with knee assessments
- •Prior articular procedures, such as transplants or ligament reconstruction to the target knee
- •Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis
- •Gout or calcium pyrophosphate (pseudogout) diseases that have flared within the previous 6 months prior to the Screening Visit
- •X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee
- •Osteonecrosis of either knee
- •Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication
- •Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee
- •Significant target knee joint infection or skin disorder/infection within the previous 6 months prior to study enrollment
- •Symptomatic OA of the hips, spine, or ankle, if it would interfere with the evaluation of the target knee
- •Known hypersensitivity to acetaminophen, EUFLEXXA™, or Phosphate buffered saline solution
- •Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the entire study period
- •Recurrent medical history of severe allergic or immune-mediated reactions or other immune disorders
- •Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation
- •Current treatment or treatment within the previous 2 years prior to the Screening Visit for any malignancy unless specific written permission is provided by the Sponsor (excluding basal cell or squamous cell carcinoma of the skin)
- •Active liver disease based on liver profile of AST, ALT, and conjugated bilirubin >2 times the upper limit of normal
- •Renal insufficiency based on serum creatinine >2.0 mg/dL
- •Any clinically significant laboratory value based on clinical history that the Investigator feels may affect the study evaluation
- •Any intercurrent chronic disease or condition that may interfere with the completion of the 6-month (or 12-month) follow-up of the study, such as liver disease, severe coronary disease, drug abuse, disordered mental state, or other clinically significant condition
- •Current alcoholism, and/or any known current addiction to pain medications
- •Any clinically significant finding that would place the patient at health risk, impact the study, or affect the completion of the study
- •Any psychiatric illness that would prevent comprehension of the details and nature of the study
- •Participation in any experimental drug or device study within the 6 months prior to the Screening Visit
结局指标
主要结局
Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
时间窗: Weeks 0, 26
The level of pain is estimated by the participant following a walk of 50 feet in length which is observed by the investigator. Pain estimates were evaluated on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed.
Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
时间窗: Weeks 0 and 26
The percent difference in participant pain recorded by the participant during a walk of 50 feet in length between the baseline (week 0) and week 26 scores. Scores are measured on a visual analog scale of 100 millimeters; a score of 0 millimeters meaning no pain was observed; a score of 100 millimeters meaning extreme pain was observed.
Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52
时间窗: weeks 26 and 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Range of motion indicates the flexibility of the knee, and is measured by the number of degrees between when the knee is hyper-extended and when the knee is flexed.
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
时间窗: weeks 26 and 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Tenderness of the knee was subjectively rated by participants as none, mild, moderate or severe.
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
时间窗: weeks 26 and 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Local warmth of the target knee was recorded as Yes (warmth present) or No (knee was not warmer than expected).
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
时间窗: weeks 26 and 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Redness of the knee was subjectively rated as Yes (knee was red) and No (knee was not red).
次要结局
- Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study(weeks -1 and 26)
- Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study for a Subpopulation of Participants With More Severe Knee Pain(weeks -1, 0, and 26)
- Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12(Week 12)
- Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26(Week 26)
- Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12(Week 12)
- Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26(week 26)
- Change From Baseline in Patient Global Assessment of Knee Pain at Week 26(Weeks 0 and 26)
- Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26.(Weeks 0 and 26)
- Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26(Weeks 0, 26)
- Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26(weeks 0 and 26)
- Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26(weeks 0 and 26)
- Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26(Weeks 0, 26)
- Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test(Weeks 0 and 26)
- Observed Pain Scores on the 50-foot Walk Test During the Extension Study(Baseline (week 26), week 52)
- Mean Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Extension Study(Extension baseline (week 26), week 52)
- Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52(Week 52 (Extension Study))
- Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52.(Extension baseline (week 26 pre-dose), week 52)