A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO AND ACTIVE-CONTROLLED, MULTICENTER, PARALLEL-GROUP STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB IN ADULT SUBJECTS WITH CHRONIC LOW BACK PAIN
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,832
- 试验地点
- 516
- 主要终点
- Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16
研究概览
简要总结
This study will investigate the efficacy and safety of tanezumab 5 mg and 10 mg administered by subcutaneous injection seven times at 8 week intervals (56 weeks). The primary objective of this study is to evaluate the effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. Secondary objectives are to evaluate the long-term safety and effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. In addition, the study will evaluate the effectiveness and long term safety profile of tanezumab treatment for chronic low back pain compared to tramadol Prolonged Release (PR), a medication commonly utilized for the treatment of chronic low back pain.
详细描述
This is a randomized, double blind, placebo and active controlled, multicenter, parallel group Phase 3 study of the efficacy and safety of tanezumab when administered by SC injection for up to 56 weeks in subjects with chronic low back pain. Approximately 1800 subjects will be randomized to 1 of 4 treatment groups in a 2:2:2:3 ratio (ie, 400 subjects per treatment group for the placebo, tanezumab 5 mg and tanezumab 10 mg treatment groups and 600 subjects in the tramadol PR treatment group). Treatment groups will include: 1.) Placebo administered SC at an 8 week interval plus placebo matching tramadol PR up to Week 16. At the Week 16 visit, subjects in this group who meet the efficacy responder criteria will be switched in a blinded fashion in a 1:1 ratio to either tanezumab 5 mg or tanezumab 10 mg administered SC at an 8 week interval plus placebo matching tramadol PR to Week 56; 2.)Tanezumab 5 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 3.) Tanezumab 10 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 4.) Oral tramadol PR plus placebo administered SC at an 8 week interval to Week 56. The study is designed with a total duration (post randomization) of up to 80 weeks and will consist of three periods: Screening (up to a maximum of 37 days; includes a Washout Period and an Initial Pain Assessment Period), a Double blind Treatment Period (comprised of a 16 week Primary Efficacy Phase and a 40 week Long Term Safety and Efficacy Phase), and a Follow up Period (24 weeks). The Screening Period (beginning up to 37 days prior to Randomization) includes a Washout Period (lasting 2 32 days), if required, and an Initial Pain Assessment Period (the 5 days prior to Randomization/Baseline). Prior to entering the study, subjects must have a documented history of previous inadequate treatment response to medications in 3 different categories of agents commonly used to treat and generally considered effective for the treatment of chronic low back pain.
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
- •Chronic low back pain ≥3 months in duration, Quebec Task Force in Spinal Disorders class 1 or 2, with documented history of previous inadequate treatment response to at least 3 different categories of agents commonly used and generally considered effective for the treatment of chronic low back pain.
排除标准
- •-Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) criteria.
- •Subjects who have Kellgren Lawrence Grade > or =2 radiographic evidence of hip or Grade > or=3 radiographic evidence of knee osteoarthritis will be excluded;
- •History or radiographic evidence of other diseases that could confound efficacy or safety assessments (e.g., rheumatoid arthritis).
- •History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
- •Signs and symptoms of clinically significant cardiac disease within 6 months of the study (e.g., unstable angina, myocardial infarction, resting bradycardia, poorly controlled or untreated hypertension) as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the Investigator would render a subject unsuitable to participate in the study
- •History, diagnosis, or signs and symptoms of clinically significant neurological disease (e.g., transient ischemic attack, stroke, peripheral or autonomic neuropathy) as specified in the protocol
- •Subjects with evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol.
结局指标
主要结局
Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16
时间窗: Baseline, Week 16
Average low back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive response technology (IRT). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.
次要结局
- Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo(Baseline, Week 16)
- Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64(Baseline, Week 64)
- Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80: Observed Data(Baseline, Weeks 64 and 80)
- Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Percentage of Participants Achieving Average LBPI Reduction of >=30 Percent(%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Week 64: Observed Data(Baseline, Week 64)
- Percentage of Participants Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Percentage of Participants With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56(Baseline, Weeks 16, 24 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Worst Pain at Week 64: Observed Data(Baseline, Week 64)
- Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16(Baseline, Week 16)
- Change From Baseline in Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56(Baseline, Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56)
- Percentage of Participants With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)(Baseline, Weeks 16, 24 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Scores Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Week 64: Observed Data(Baseline, Week 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Week 64: Observed Data(Baseline, Week 64)
- Number of Participants Who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56(Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64(Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64)
- Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Week 64: Observed Data(Baseline, Week 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Average Pain at Week 64: Observed Data(Baseline, Week 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Week 64: Observed Data(Baseline, Week 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Number of Participants Who Withdrew Due to Lack of Efficacy(Baseline up to Week 56)
- Number of Participants Who Took Rescue Medication During Week 64: Observed Data(Week 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value(Baseline, Weeks 8, 16, 24, 40, 56 and 64)
- Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data(Baseline)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64(Baseline, Weeks 16, 56 and 64)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Week 64: Observed Data(Baseline, Week 64)
- European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score(Baseline, Weeks 8, 16, 24, 40 and 56)
- Time to Discontinuation Due to Lack of Efficacy(Baseline up to Week 56)
- Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF)(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56)
- Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain(Baseline, Weeks 64 and 80)
- Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56(Weeks 16 and 56)
- Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56(Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56)
- Number of Days of Rescue Medication Used at Week 64(Week 64)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling?(Weeks 16 and 56)
- Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline(Baseline up to Week 80)
- Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline(Baseline up to Week 80)
- Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80(Screening (up to maximum of 37 days prior to Baseline), Weeks 24, 56 and 80)
- Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16(Weeks 2, 4, 8, 12 and 16)
- Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80)
- Number of Participants With Anti Tanezumab Antibodies(Baseline, Weeks 8, 16, 32, 40, 48, 56, 64 and 80)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?(Weeks 16 and 56)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 80)
- Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 56(Baseline up to Week 56)
- Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80)
- Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain(Baseline, Weeks 64 and 80)
- Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things(Baseline, Weeks 64 and 80)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain?(Weeks 16 and 56)
- Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80)
- Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80(Baseline, Weeks 16, 56 and 80)
- Percentage of Participants With Adjudicated Joint Safety Outcomes(Baseline up to Week 80)
- Percentage of Participants With Total Joint Replacements(Baseline up to Week 80)
- Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16, 56 and 80(Baseline, Weeks 16, 56 and 80)
- Number of Participants With Confirmed Orthostatic Hypotension(Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80)