Long-Term Analgesic Efficacy And Safety Of Tanezumab Alone Or In Combination With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Versus NSAIDs Alone In Patients With Osteoarthritis Of The Knee Or Hip

Study Overview
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Brief Summary
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The purpose of this study is to investigate the long-term analgesic efficacy and safety of tanezumab for patients with osteoarthritis (OA) of the knee or hip currently experiencing partial benefit from, and are tolerating, non-steroidal anti-inflammatory drug (NSAID) therapy.

Detailed Description
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This study was terminated on 28 October 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.

Official Title
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A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY OF THE LONG-TERM ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ALONE OR IN COMBINATION WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) VERSUS NSAIDS ALONE IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP

Conditions
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Osteoarthritis, Arthritis

Intervention / Treatment
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* Drug: NSAID
* Biological: tanezumab
* Biological: tanezumab
* Biological: tanezumab
* Drug: NSAID
* Biological: tanezumab
* Drug: NSAID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence x-ray grade equal to, or greater than, 2. Patients must be experiencing some benefit from their current stable dose regimen of oral NSAID therapy of either naproxen 500-1000 mg/day or celecoxib 200 mg/day (either 100 mg BID or 200 mg QD) and be tolerating their NSAID regimen. Pain level and function levels as required by the protocol at Screening and Baseline. Willing to discontinue all non-study pain medications for osteoarthritis except rescue medication (acetaminophen) and not use prohibited pain medications throughout the duration of the study except as permitted per protocol. Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria: Pregnant women. BMI greater than 39. Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to sever pain that may confound assessments or self-evaluation of the pain associated with OA. Signs and symptoms of clinically significant cardiac disease with 6 months prior to screening. Diagnosis of TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities. History, diagnosis, signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder. At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 1.7 mg/dL (men) or 1.5 mg/dL (women). Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to screening. Known hypersensitivity to NSAIDs or cyclooxygenase inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IV Placebo + NSAID<br>Oral NSAID | Drug: NSAID<br>* IV doses of placebo (to match tanezumab) every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks<br>|
| Experimental: Tanezumab 5 mg<br>IV tanezumab 5 mg every 8 weeks (through Week 48) | Biological: tanezumab<br>* IV tanezumab 5 mg every 8 weeks (through Week 48) and oral placebo for NSAID BID from Weeks 2 through 56<br>|
| Experimental: Tanezumab 10 mg<br>IV tanezumab 10 mg every 8 weeks (through Week 48) | Biological: tanezumab<br>* IV tanezumab 10 mg every 8 weeks (through Week 56) and oral placebo for NSAID BID from Weeks 2 through 56<br>|
| Experimental: Tanezumab 5 mg + NSAID<br>IV doses of tanezumab 5 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks | Biological: tanezumab<br>* IV tanezumab 5 mg every 8 weeks (through Week 48)<br>Drug: NSAID<br>* Oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks<br>|
| Experimental: Tanezumab 10 mg + NSAID<br>IV doses of tanezumab 10 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks | Biological: tanezumab<br>* IV tanezumab 10 mg every 8 weeks (through Week 48)<br>Drug: NSAID<br>* Oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Week 16 | 
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16 | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip).The WOMAC physical function subscale was comprised of 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis of 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 (maximum difficulty), where higher scores indicated worse physical function. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Week 16 | 
| Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Week 16 | Patient global assessment of osteoarthritis was assessed by asking a question from participants: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants responded by using a 5-point likert scale ranging from 1=very good (asymptomatic 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 which are intolerable and inability to carry out all normal activities). Higher scores indicating worse condition. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Weeks 2, 4, 8, 12, and 24 | 
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip).The WOMAC physical function subscale was comprised of 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis of 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 (maximum difficulty), where higher scores indicated worse physical function. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Weeks 2, 4, 8, 12, and 24 | 
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip).The WOMAC physical function subscale was comprised of 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis of 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 (maximum difficulty), where higher scores indicated worse physical function. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Weeks 2, 4, 8, 12, 24, 32, 40, 48, and 56 | 
| Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | Patient global assessment of osteoarthritis was assessed by asking a question from participants: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants responded by using a 5-point likert scale ranging from 1=very good (asymptomatic and no limitation of normal activities, 2= 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 which are intolerable and inability to carry out all normal activities). Higher scores indicating worse condition. | Baseline, Weeks 2, 4, 8, 12, and 24 | 
| Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | Patient global assessment of osteoarthritis was assessed by asking a question from participants: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants responded by using a 5-point likert scale ranging from 1=very good (asymptomatic and no limitation of normal activities, 2= 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 which are intolerable and inability to carry out all normal activities). Higher scores indicating worse condition. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response: Baseline Observation Carried Forward (BOCF) | Participants were considered as OMERACT-OARSI responder: if the improvement from baseline to week of interest was greater than or equal to (>=) 50 percent and >=2 units in WOMAC pain subscale or WOMAC physical function subscale score, or at least 2 of the following 3 being true: improvement from baseline to week of interest was >=20 percent and >=1 unit in 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [worst possible pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = worse physical function) and PGA of osteoarthritis (score: 1 [very good] to 5 [very poor], higher score = worse condition). | Weeks 2, 4, 8, 12, 16, and 24 | 
| Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response: Last Observation Carried Forward (LOCF) | Participants were considered as OMERACT-OARSI responder: if the improvement from baseline to week of interest was >=50 percent and >=2 units in WOMAC pain subscale or WOMAC physical function subscale score, or at least 2 of the following 3 being true: improvement from baseline to week of interest was >=20 percent and >=1 unit in 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [worst possible pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = worse physical function) and PGA of osteoarthritis (score: 1 [very good] to 5 [very poor], higher score = worse condition). | Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Percentage of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score From Baseline at Weeks 2, 4, 8, 12, 16, and 24: BOCF | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). The WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Percentage of participants who experienced an improvement (reduction) of >=30%, >=50%, >=70%, or >=90% in the WOMAC pain subscale scores from Baseline were reported. | Baseline, Weeks 2, 4, 8, 12, 16, and 24 | 
| Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Percentage of participants who experienced an improvement (reduction) of >=30 percent, >=50%, >=70%, or >=90% in the WOMAC pain subscale scores from Baseline were reported. | Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Number of participants who experienced reduction (as percent) of >0% to >=100% from Baseline in WOMAC pain subscale scores at Week 16 were reported. | Baseline, Week 16 | 
| Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was 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 mean of the scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Number of participants who experienced reduction (as percent) of >0% to >=100% from Baseline in WOMAC pain subscale scores at Week 16 were reported. | Baseline, Week 16 | 
| Percentage of Participants With Improvement of At Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, and 24: Baseline Observation Carried Forward (BOCF) | Patient global assessment of osteoarthritis was assessed by asking a question from participants: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants responded by using a 5-point likert scale ranging from 1=very good (asymptomatic and no limitation of normal activities, 2= 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 which are intolerable and inability to carry out all normal activities). Higher scores indicating worse condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value. Percentage of participants who showed an improvement of >=2 points on scale were reported. | Weeks 2, 4, 8, 12, 16, and 24 | 
| Percentage of Participants With Improvement of Atleast 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56: Last Observation Carried Forward (LOCF) | Patient global assessment of osteoarthritis was assessed by asking a question from participants: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants responded by using a 5-point likert scale ranging from 1=very good (asymptomatic and no limitation of normal activities, 2= 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 which are intolerable and inability to carry out all normal activities). Higher scores indicating worse condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value. Percentage of participants who showed an improvement of >=2 points on scale were reported. | Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC stiffness subscale was a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis of the index joint (knee or hip) during the past 48 hours. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). It was calculated as mean of the scores from 2 individual questions scored on NRS of 0 (no stiffness) to 10 (worst stiffness), with higher scores indicate more stiffness. Total score range for WOMAC stiffness subscale score was 0 (no stiffness) to 10 (worst stiffness), where higher scores indicated more stiffness. | Baseline, Weeks 2, 4, 8, 12, 16, and 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC stiffness subscale was a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in the index joint (knee or hip) during the past 48 hours. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). It was calculated as mean of the scores from 2 individual questions scored on NRS of 0 (no stiffness) to 10 (worst stiffness), with higher scores indicate more stiffness. Total score range for WOMAC stiffness subscale score was 0 (no stiffness) to 10 (worst stiffness), where higher scores indicated more stiffness. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). Each item is scored on a 0 to 10 NRS scale, where higher scores indicate higher pain/stiffness or worse function. WOMAC average score was calculated as the mean of 3 WOMAC subscale scores (pain, physical function and stiffness). Total score range was 0 (no response) to 10 (worse response), where higher score indicated worse response. | Baseline, Weeks 2, 4, 8, 12, 16, and 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). Each item is scored on a 0 to 10 NRS scale, where higher scores indicate higher pain/stiffness or worse function. WOMAC average score was calculated as the mean of 3 WOMAC subscale scores (pain, physical function and stiffness). Total score range was 0 (no response) to 10 (worse response), where higher score indicated worse response. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| 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 Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Participants responded about the amount of pain they experienced when walking on a flat surface by answering the question: How much pain have you had when walking on a flat surface?. Participants responded by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | 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 Walking on a Flat Surface at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Participants responded about the amount of pain they experienced when walking on a flat surface by answering the question: How much pain have you had when walking on a flat surface?. Participants responded by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). Participants responded about the amount of pain they experienced when going up or down stairs by answering the question: How much pain have you had when going up or down the stairs? Participants responded by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | 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 Down Stairs at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). Participants responded about the amount of pain they experienced when going up or down stairs by answering the question: How much pain have you had when going up or down the stairs? Participants responded by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24: Baseline Observation Carried Forward (BOCF) | The SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional, domain 8= mental health. Total score for each domain are scaled 0 (minimum) to 100 (maximum), where higher scores represent better health status. | Baseline, Weeks 12 and 24 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Weeks 12, 24, 40 and 56: Last Observation Carried Forward (LOCF) | The SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional, domain 8= mental health. Total score for each domain are scaled 0 (minimum) to 100 (maximum), where higher scores represent better health status. | Baseline, Weeks 12, 24, 40, and 56 | 
| Number of Participants Who Had Discontinued Study Due to Lack of Efficacy |  | Baseline up to Week 56 | 
| Time to Discontinuation Due to Lack of Efficacy | Time to discontinuation due to lack of efficacy was defined as the time interval from the date of study drug administration up to the date of discontinuation of participant from study due to lack of efficacy. | Baseline up to Week 56 | 
| Change From Baseline in Percent Work Time Missed Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions (Q) are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent work time missed due to health problem: Q2/(Q2+Q4). The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Week 24 | 
| Change From Baseline in Percent Work Time Missed Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent work time missed due to health problem: Q2/(Q2+Q4). The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Week 24 and 56 | 
| Change From Baseline in Percent Impairment While Working Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent impairment while working due to health problem: Q5/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Week 24 | 
| Change From Baseline in Percent Impairment While Working Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent impairment while working due to health problem: Q5/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Weeks 24 and 56 | 
| Change From Baseline in the Percent Overall Work Impairment Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): BOCF | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent overall work impairment due to health problem: Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))*(Q5/10)]. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Week 24 | 
| Change From Baseline in the Percent Overall Work Impairment Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): LOCF | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent overall work impairment due to health problem: Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))*(Q5/10)]. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Weeks 24 and 56 | 
| Change From Baseline in the Percent Activity Impairment Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent activity impairment due to health problem: Q6/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Week 24 | 
| Change From Baseline in the Percent Activity Impairment Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF) | The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated: Percent activity impairment due to health problem: Q6/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity. | Baseline, Weeks 24, and 56 | 
| Percentage of Participants Who Used Rescue Medication: Observed Data | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day for maximum of 3 days within a week could be taken as rescue medication. Percentage of participants with any use of rescue medication during each study interval were summarized. | Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48 and 49-56 | 
| Percentage of Participants Who Used Rescue Medication: Last Observation Carried Forward (LOCF) | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day for maximum of 3 days within a week could be taken as rescue medication. Percentage of participants with any use of rescue medication during each study interval were summarized. | Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48 and 49-56 | 
| Amount of Rescue Medication Used | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days in a week could be taken as rescue medication. The total dosage of acetaminophen in mg used during the specified time intervals were summarized. | Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48, and 49-56 | 
| Change From Baseline in Medial Minimum Joint Space Width of the Index Knee at Week 56 |  | Baseline, Week 56 | 
| Change From Baseline in Minimum Joint Space Width of the Index Hip at Week 56 |  | Baseline, Week 56 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 64 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events. | Baseline up to Week 64 | 
| Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Observed Data | The Neuropathy Impairment Score is the sum of scores over all 37 items from both the left and right side. The neurological impairment score assessed strength of groups of muscles of the head and neck, upper limbs and lower limbs, deep tendon reflexes and sensation (tactile, vibration, joint position sense, and pin prick) of index fingers and great toes through neurological examination. NIS calculated scoring muscle weakness (0=normal, 1=25% weak, 2=50% weak, 3=75% week, 3.25= move against gravity, 3.5=movement gravity eliminated, 3.75= muscle flicker no movement, 4=paralysis), scoring reflexes (0=normal, 1=reduced. 2=absent), scoring sensation (0=normal, 1=decreased, 2=absent). For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56 | 
| Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF) | The Neuropathy Impairment Score is the sum of scores over all 37 items from both the left and right side. The neurological impairment score assessed strength of groups of muscles of the head and neck, upper limbs and lower limbs, deep tendon reflexes and sensation (tactile, vibration, joint position sense, and pin prick) of index fingers and great toes through neurological examination. NIS calculated scoring muscle weakness (0=normal, 1=25% weak, 2=50% weak, 3=75% week, 3.25= move against gravity, 3.5=movement gravity eliminated, 3.75= muscle flicker no movement, 4=paralysis), scoring reflexes (0=normal, 1=reduced. 2=absent), scoring sensation (0=normal, 1=decreased, 2=absent). For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56 | 
| Plasma Trough (Pre-dose) Concentration of Tanezumab |  | Predose on Day 1, Weeks 16, 24, 40, and 56 | 
| Number of Participants With Intravenous (IV) Doses of Study Medication | Number of participants are reported based on the maximum number of IV doses of either tanezumab or placebo received. | Baseline up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal antibody, nerve growth factor (NGF), anti-NGF, tanezumab, PF-04383119, RN624, osteoarthritis (OA)