A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF A DOSE TITRATION REGIMEN FOR THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 698
- 试验地点
- 174
- 主要终点
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy of a titration arm of tanezumab in which treatment is started at a lower dose (2.5 mg) and increased to a higher dose (5 mg) at Week 8, compared to giving 2 doses of tanezumab 2.5 mg or 2 doses of placebo. The study also evaluates the safety of the treatment regimens.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Osteoarthritis of the knee or hip confirmed by X-ray
- •Documented history that subject tried the following medications and had insufficient pain relief or is cannot take or tolerate them: acetaminophen, NSAIDs and either tramadol or opioids
- •Meet the protocol requirements for pain at screening and pain, physical function and patient global assessment of osteoarthritis at baseline
- •Willing to discontinue all pain medications except study medication and rescue medication during the course of the study and use those as directed per protocol
- •Women able to have children must agree to use 2 forms of contraception during the study
排除标准
- •Body Mass Index (BMI) greater than 39
- •History of diseases other than osteoarthritis in a shoulder, hip or knee (example, rheumatoid arthritis, gout, joint infections, osteonecrosis)
- •Patients with x-ray showing joint conditions such as osteonecrosis (dead bone) or certain types of fractures
- •Patients who have had significant trauma or surgery to a knee, hip or shoulder within the previous year
- •Planned surgical procedure during the study
- •Patients who are largely or wholly incapacitated (example bedridden or confined to a wheelchair, permitting little or no self-care)
- •Patients who would be unwilling or unable to undergo joint replacement surgery if one eventually became necessary
- •Patients with significant conditions other than osteoarthritis that could interfere with assessment of pain in the joints (example fibromyalgia, lupus erythematosus)
- •Patients with significant heart, neurological or psychiatric diseases
- •Patients who had cancer other than certain skin cancers within the past 5 years
- •Patients with alcohol, analgesic (pain medications) or drug abuse within the past 2 years
- •Women who are pregnant, breast-feeding or intending to become pregnant or breast-feed during the course of the study.
结局指标
主要结局
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
时间窗: Baseline, Week 16
WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16
时间窗: Baseline, Week 16
PGA of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
时间窗: Baseline, Week 16
WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
次要结局
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8 and 12(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24(Baseline, Week 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8 and 12(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24(Baseline, Week 24)
- Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8 and 12(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 24(Baseline, Week 24)
- Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index(Weeks 2, 4, 8, 12, 16 and 24)
- Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response(Week 2, 4, 8, 12, 16 and 24)
- Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16(Baseline to Week 16)
- Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response(Weeks 2, 4, 8, 12, 16 and 24)
- Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16(Baseline to Week 16)
- Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis(Weeks 2, 4, 8, 12, 16 and 24)
- Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16(Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16)
- Change From Baseline for Average Pain Score in the Index Joint at Weeks 20 and 24(Baseline, Weeks 20 and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 24(Baseline, Week 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 24(Baseline, Week 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 24(Baseline, Week 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Week 24(Baseline, Week 24)
- Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline(Baseline)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Week 16(Baseline and Week 16)
- European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Dimensions Score(Baseline, Weeks 8 and 16)
- European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score/Index Value(Baseline, Weeks 8 and 16)
- Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Time to Discontinuation Due to Lack of Efficacy(Baseline up to Week 16)
- Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12 and 16(Week 2, 4, 8, 12 and 16)
- Number of Participants Who Took Rescue Medication During Week 24(Week 24)
- Number of Days of Rescue Medication Use at Week 2, 4, 8, 12 and 16(Week 2, 4, 8, 12, 16)
- Number of Days of Rescue Medication Use at Week 24(Week 24)
- Amount of Rescue Medication Taken at Weeks 2, 4, 8, 12 and 16(Week 2, 4, 8, 12, 16)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 40)
- Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 40)
- Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline(Baseline up to Week 40)
- Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis(Baseline, Weeks 24 and 40)
- Number of Participants Who Withdrew Due to Lack of Efficacy(Baseline up to Week 16)
- Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 40(Baseline, Weeks 2, 4, 8, 12, 16, 24, 40)
- Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12,16, 24, 40(Baseline, Weeks 2, 4, 8, 12, 16, 24 and 40)
- Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16 and 40(Baseline, Weeks 16, 40)
- Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16 and 40(Baseline, Weeks 16 and 40)
- Percentage of Participants With Adjudicated Joint Safety Outcomes(Baseline up to Week 40)
- Percentage of Participants With Total Joint Replacements(Baseline up to Week 40)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8,12,16, 24 and 40(Baseline, Weeks 2, 4, 8,12,16, 24 and 40)
- Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline(Baseline up to Week 40)
- Number of Participants With Confirmed Orthostatic Hypotension(Baseline up to Week 40)
- Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Weeks 24 and 40(Baseline, Weeks 24 and 40)
- Number of Participants With Anti-Tanezumab Antibodies(Baseline, Weeks 8,16, 24 and 40)