A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF 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
- 849
- 试验地点
- 146
- 主要终点
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24
研究概览
简要总结
Tanezumab is a monoclonal antibody that binds to and inhibits the actions of nerve growth factor (NGF). The Nerve Growth Factor Inhibitor (NGFI) class may offer an important breakthrough in the treatment of chronic pain and is under clinical investigation for the treatment of pain associated with osteoarthritis or other chronic pain conditions.
The primary objective of this study is to demonstrate superior efficacy of tanezumab 5 mg and 2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24 in subjects with osteoarthritis of the knee or hip. The 2.5 mg dose was shown to provide efficacy benefits with a favorable safety profile when administered intravenously in previous Phase 3 clinical trials. The 5 mg dose is expected to provide added efficacy benefit over the 2.5 mg dose based on data from previous studies.
详细描述
This is a randomized, double blind, placebo controlled, parallel group multicenter Phase 3 study of the efficacy and safety of tanezumab when administered by SC injection for 24 weeks compared to placebo in subjects with osteoarthritis of the knee or hip. A total of approximately 810 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (ie, 270/group). The randomization will be stratified by index joint (hip or knee), and most severe Kellgren-Lawrence grade (of any knee or hip joint) at study entry (grade 2, 3 or 4). Subjects will receive up to three SC doses of one of the following treatments at an 8-week interval between each injection:
- tanezumab 2.5 mg;
- tanezumab 5 mg;
- Placebo to match tanezumab. The study is designed with a total (post-randomization) duration of 48 weeks and will consist of three periods: Screening (up to 37 days), Double-blind Treatment (24 weeks) and Safety Follow-up (24 weeks). The Screening Period (beginning up to 37 days prior to Randomization) includes a Washout Period (lasting a minimum of 2 days for all prohibited pain medications), if required, and an Initial Pain Assessment Period (the 7 days prior to Randomization/Baseline).
Week 24 is the landmark analysis in this study. Subjects who do not complete the Double-blind Treatment period will enter and complete the 24-week Early-termination follow-up period.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of osteoarthritis of the index hip or knee based on American College of Rheumatology criteria with Kellgren Lawrence x-ray Grade of at least 2 as diagnosed by the Central Reader
- •A history of insufficient pain relief from acetaminophen along with a history of insufficient pain relief from, inability to tolerate or contraindication to taking NSAIDs, and tramadol or opioid treatments.
- •WOMAC Pain subscale score of at least 5 in the index hip or knee at Screening.
- •Be willing to discontinue all non study pain medications for osteoarthritis and not use prohibited pain medications throughout the duration of the study.
- •Female subjects of childbearing potential must agree to comply with protocol specified contraceptive requirements.
排除标准
- •Subjects exceeding protocol defined BMI or body weight limits.
- •History of other diseases specified in the protocol (e.g. inflammatory joint diseases, crystalline diseases such as gout or pseudogout) that may involve the index joint and that could interfere with efficacy assessments.
- •Radiographic evidence of protocol specified bone or joint conditions in any screening radiograph as determined by the central radiology reviewer.
- •A history of osteonecrosis or osteoporotic fracture.
- •History of significant trauma or surgery to a knee, hip or shoulder within the previous year.
- •Planned surgical procedure during the duration of the study.
- •Presence of conditions (e.g. fibromyalgia, radiculopathy) associated with moderate to severe pain that may confound assessments or self evaluation of osteoarthritis pain.
- •Signs or symptoms of carpal tunnel syndrome in the year prior to Screening.
- •Considered unfit for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required.
- •History of intolerance or hypersensitivity to acetaminophen or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated.
- •Use of prohibited medications without the appropriate washout period prior to Screening or Initial Pain Assessment Period.
- •History of cancer within 5 years of Screening, except for cutaneous basal cell or squamous cell cancer resolved by excision.
- •Subjects with signs and symptoms of clinically significant cardiac disease as described in the protocol.
- •Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits that would preclude completion of required study activities.
- •History, diagnosis, or signs and symptoms of clinically significant neurological disease such as but not limited to peripheral or autonomic neuropathy.
- •History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder.
- •History of known alcohol, analgesic or drug abuse within 2 years of Screening.
- •Previous exposure to exogenous NGF or to an anti-NGF antibody.
- •History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein.
- •Poorly controlled hypertension as defined in the protocol or taking an antihypertensive that has not been stable for at least 1 month prior to Screening.
- •Evidence of protocol defined orthostatic hypotension at Screening.
- •Disqualifying score on the Survey of Autonomic Symptoms questionnaire at Screening.
- •Screening AST, ALT, serum creatinine or HbA1c values that exceed protocol defined limits.
- •Presence of drugs of abuse in screening urine toxicology panel.
- •Positive hepatitis B, hepatitis C or HIV test results indicative of current infection.
- •Participation in other investigational drug studies within protocol defined time limits.
- •Pregnant, breastfeeding or female subjects of childbearing potential who are unwilling or unable to follow protocol required contraceptive requirements.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator, would make the subject inappropriate for entry into this study.
研究组 & 干预措施
Low dose
Investigational product
干预措施: Tanezumab (Drug)
Placebo
Investigational product
干预措施: Placebo (Drug)
High dose
Investigational product
干预措施: Tanezumab (Drug)
结局指标
主要结局
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24
时间窗: Baseline, Week 24
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA). The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA 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). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24
时间窗: Baseline, Week 24
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. 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 OA 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. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Week 24
时间窗: Baseline, Week 24
PGA of OA 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.
次要结局
- Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index(Weeks 2, 4, 8, 12, 16, 24 and 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32(Baseline, Week 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32(Baseline, Week 32)
- Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24(Baseline, Weeks 16 and 24)
- Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis(Weeks 2, 4, 8, 12, 16, 24 and 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32(Baseline, Week 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32(Baseline, Week 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32(Baseline, Week 32)
- Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis(Baseline, Weeks 32 and 48)
- Percentage of Participants With Adjudicated Joint Safety Outcomes(Baseline up to Week 48)
- Number of Days of Rescue Medication Used at Week 32(Week 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response(Weeks 2, 4, 8, 12, 16, 24 and 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24(Baseline, Weeks 2, 4, 8, 12, 16 and 24)
- Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline(Baseline)
- 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, 24 and 32)
- Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24(Baseline, Weeks 16 and 24)
- Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24(Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24)
- Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32(Baseline, Weeks 28 and 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24(Baseline, Weeks 2, 4, 8, 12, 16 and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24(Baseline, Weeks 2, 4, 8, 12, 16 and 24)
- Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32(Baseline, Week 32)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Participant Reported Treatment Impact Assessment-Overall, How Satisfied Are You With The Drug That You Received in This Study?(Weeks 16 and 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, 16 and 24(Baseline, Weeks 2, 4, 8, 12, 16 and 24)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24(Baseline, Weeks 8, 16 and 24)
- European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value(Baseline, Weeks 8, 16 and 24)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Osteoarthritis Pain Before Enrolling?(Weeks 16 and 24)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Participant Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?(Weeks 16 and 24)
- Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things(Baseline, Weeks 32 and 48)
- Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Number of Participants Who Took Rescue Medication During Week 32(Week 32)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32(Baseline, Week 32)
- Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Participant Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Osteoarthritis Pain?(Weeks 16 and 24)
- Number of Participants Who Withdrew Due to Lack of Efficacy(Baseline up to Week 24)
- Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16 and 24(Weeks 2, 4, 8, 12, 16 and 24)
- Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline(Baseline up to Week 48)
- European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score(Baseline, Weeks 8, 16 and 24)
- Time to Discontinuation Due to Lack of Efficacy(Baseline up to Week 24)
- Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24(Weeks 2, 4, 8, 12, 16 and 24)
- Amount of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24(Weeks 2, 4, 8, 12, 16 and 24)
- Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study(Baseline up to Week 48)
- Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48)
- Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48(Baseline, Weeks 24 and 48)
- Number of Participants With Confirmed Orthostatic Hypotension(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48)
- Number of Participants With Anti Tanezumab Antibodies(Baseline, Weeks 8,16, 24, 32 and 48)
- Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis(Baseline, Weeks 32 and 48)
- Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline(Baseline up to Week 48)
- Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 24 and 48(Baseline, Weeks 24 and 48)
- Percentage of Participants With Total Joint Replacements(Baseline up to Week 48)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study(Baseline up to Week 48)
- Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48(Baseline, Weeks 2, 4, 8, 12,16, 24, 32 and 48)
- Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24(Baseline, Week 24)