Tanezumab in Osteoarthritis Of The Hip

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the efficacy and safety of 3 doses of tanezumab in osteoarthritis of the hip in patients

Official Title
-----------------
A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE HIP.

Conditions
-----------------
Arthritis, Osteoarthritis, Osteoarthritis, Hip

Intervention / Treatment
-----------------
* Biological: tanezumab
* Biological: tanezumab
* Biological: tanezumab
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Osteoarthritis of the hip according to ACR criteria with Kellgren-Lawrence x-ray grade of 2 Unwilling or unable to take non-opiate pain medications, for whom non-opiate pain medications have not provided adequate pain relief or are candidates for Hip injections, arthroplasty or replacement surgery Pain level and function levels as required by the protocol at Screening and Baseline Willing to discontinue pain medications (acetaminophen will be permitted up to a certain level) before and during the study Must agree to the contraceptive requirements of the protocol if applicable Must agree to the treatment plan, scheduled visits, and procedures of the protocol Exclusion Criteria: Pregnancy BMI greater than 39 Other severe pain, significant cardiac, neurological or psychological conditions, or above the protocol limits for laboratory and blood pressure results

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tanezumab 10 mg<br>Tanezumab 10 mg IV every 8 weeks | Biological: tanezumab<br>* Tanezumab 10 mg IV every 8 weeks<br>|
| Experimental: Tanezumab 5 mg<br>Tanezumab 5mg IV every 8 weeks | Biological: tanezumab<br>* Tanezumab 5mg IV every 8 weeks<br>|
| Experimental: Tanezumab 2.5 mg<br>Tanezumab 2.5 mg IV every 8 weeks. | Biological: tanezumab<br>* Tanezumab 2.5 mg IV every 8 weeks.<br>|
| Experimental: Placebo<br>Placebo | Biological: Placebo<br>* Placebo to match tanezumab IV every 8 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint 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 is 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline (Day 1), Week 16 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse 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 Patient Global Assessment (PGA) of Osteoarthritis at Week 16: Baseline Observation Carried Forward (BOCF) | Participants answered: Considering all the ways your osteoarthritis in your hip joint affects you, how are you doing today?, participants responded by using a 5-point scale where 1 = very good (no symptom and limitation of normal activities) and 5 = very poor (very severe symptoms and inability to carry out normal activities), where lower scores indicates better condition. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in Pain Subscale Score at Week 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint 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 is 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Week 2, 4, 8, 12, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in Pain Subscale Score at Week 2, 4, 8, 12,16 and 24: Last Observation Carried Forward (LOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint 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 is 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Subscale Score at Week 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint 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 is 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Week 2, 4, 8, 12, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Subscale at Week 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF) | Participants answered: Considering all the ways your osteoarthritis in your hip joint affects you, how are you doing today?, participants responded by using a 5-point scale where 1 = very good (no symptom and limitation of normal activities) and 5 = very poor (very severe symptoms and inability to carry out normal activities), where lower scores indicates better condition. | Baseline, Week 2, 4, 8, 12, 24 | 
| Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) | Participants answered: Considering all the ways your osteoarthritis in your hip joint affects you, how are you doing today?, participants responded by using a 5-point scale where 1 = very good (no symptom and limitation of normal activities) and 5 = very poor (very severe symptoms and inability to carry out normal activities), where lower scores indicates better condition. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Percentage of Participants With Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Response: Baseline Observation Carried Forward (BOCF) | A participant was considered as an OMERACT-OARSI responder if at least one of the following criteria were met: Improvement in WOMAC pain or physical function subscale from baseline to week of interest was greater than or equal to (>=) 50 percent (%)and absolute change of >=2 units from baseline at the week of interest, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at the week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis. Score range for PGA: 1 = very good to 5 = very poor, where higher scores=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0 [no pain] to 10 [worst possible pain], higher score=higher pain/difficulty). | Week 2, 4, 8, 12, 16, 24 | 
| Percentage of Participants With Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Response: Last Observation Carried Forward (LOCF) | A participant was considered as an OMERACT-OARSI responder if at least one of the following criteria were met: Improvement in WOMAC pain or physical function subscale from baseline to week of interest was greater than or equal to (>=) 50 percent (%)and absolute change of >=2 units from baseline at the week of interest, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at the week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis. Score range for PGA: 1 = very good to 5 = very poor, where higher scores=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0 [no pain] to 10 [worst possible pain], higher score=higher pain/difficulty). | Week 2, 4, 8, 12 ,16, 24 | 
| Percentage of Participants With at Least 30 Percent (%), and 50 % Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 2, 4, 8, 12, 16, 24: Baseline Observation Carried Forward | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint 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 is 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Percentage of participants with >=30% or >=50% reduction in WOMAC pain subscale score from baseline to specified weeks were reported. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Percentage of Participants With at Least 30 Percent (%), and 50% 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 questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a NRS of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Percentage of participants with >=30% or >=50% reduction in WOMAC pain subscale score from baseline to specified weeks were reported. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Percentage of Participants With at Least 2 Points Improvement From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8, 12 ,16 and 24: Baseline Observation Carried Forward (BOCF) | Participants answered: Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?, participants responded by using a 5-point scale where 1 = very good and 5 = very poor where lower scores indicating better condition. Percentage of participants with an improvement of greater than or equal to 2 points from baseline at specified weeks were reported. | Baseline, Week 2, 4, 8, 12 ,16, 24 | 
| Percentage of Participants With at Least 2 Points Improvement From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8, 12, 16, 24: Last Observation Carried Forward (LOCF) | Participants answered: Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?, participants responded by using a 5-point scale where 1 = very good and 5 = very poor where lower scores indicating better condition. Percentage of participants with an improvement of greater than or equal to 2 points from baseline at specified weeks were reported. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a NRS of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 were reported. | Baseline, Week 16 | 
| Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16: Last Observation Carried Forward (LOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a NRS of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 were reported. | Baseline, Week 16 | 
| Change From Baseline in Average Daily Pain Score in the Hip Joint at Week 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | Participants assessed daily average hip joint pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Post baseline weekly scores were calculated as the mean of the scores over the last 7 days prior to each assessment time point. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Week 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in hip joint during past 48 hours. It is calculated as mean of the scores from 2 individual questions each scored on numerical rating scale of 0 (minimum stiffness) to 10 (maximum stiffness), giving an overall possible mean score range of 0 (minimum stiffness) to 10 (maximum stiffness). Higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of hip joint. | Baseline, Week 2, 4, 8, 12 ,16, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) Average Score at Week 2, 4, 8, 12,16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis of hip joint. Each item is scored on a 0 (no pain) to 10 (worst possible pain) NRS scale, where higher scores indicate higher pain/stiffness or worse function. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 (no pain) to 10 (worst possible pain), where higher score indicates worse response. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) Pain Subscale Item (Pain When Walking on Flat Surface) Score at Week 2, 4, 8, 12, 16 and 24 : Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Participants answered How much pain have you had when walking on a flat surface?. Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 =extreme pain. Higher scores indicated more pain. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) Score at Week 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF) | WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Participants answered How much pain have you had when going up or down the stairs?. Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = worst possible pain, where higher scores indicating higher pain. | Baseline, Week 2, 4, 8, 12, 16, 24 | 
| Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 12 and 24: Baseline Observation Carried Forward (BOCF) | The SF-36 health survey was 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 score indicates highest level of functioning. | Baseline, Week 12, 24 | 
| Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 12 and 24: Baseline Observation Carried Forward (BOCF) | The SF-36 health survey was 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 score indicates highest level of functioning. These 8 domains were also summarized as summary scores: mental component aggregate (MCA) and physical component aggregate (PCA). Total score range for the each summary scores =0 to 100, where higher scores represented higher level of functioning. Higher summary scores indicated a better health related quality of life. | Baseline, Week 12, 24 | 
| Time to Discontinuation Due to Lack of Efficacy | Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method. | Baseline up to Week 16 | 
| Percentage of Participants Who Used Rescue Medication | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. Percentage of participants with any use of rescue medication during the particular study week were summarized. | Week 2, 4, 8, 12 ,16, 24 | 
| Duration of Rescue Medication Use | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. Number of days participant used any of the rescue medication, during the specified week were summarized. | Week 2, 4, 8, 12, 16, 24 | 
| Amount of Rescue Medication Taken | In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. The total dosage of acetaminophen in mg used during the specified week were summarized. | Week 2, 4, 8, 12, 16, 24 | 
| 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 32 that were absent before treatment or that worsened relative to pretreatment state. Adverse events included both serious and all non-serious adverse events. | Baseline up to Week 32 | 
| Change From Baseline in Neuropathy Impairment Score (NIS) at Week 2, 4, 6, 8, 12, 16 and 24 | The NIS is a standardized instrument used to evaluate participant for signs of peripheral neuropathy. Neurologic examination 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 in order to complete the NIS. The NIS is the sum of scores of over all 37 items (24 scored 0-4; 13 scored 0-2), made separately for left and right sides, giving a possible overall score range of 0 (no impairment) to 122 (severe impairment). NIS Total score range (total of both left and right sides) was 0 (no impairment) to 244 (severe impairment), where higher scores indicated increased impairment. | Baseline, Week 2, 4, 6, 8, 12, 16, 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
monoclonal antibody RN624 PF-04383119 nerve growth factor anti-nerve growth OA