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Trial record 1 of 1 for:    NCT02709486
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Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee.

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ClinicalTrials.gov Identifier: NCT02709486
Recruitment Status : Completed
First Posted : March 16, 2016
Results First Posted : June 26, 2019
Last Update Posted : June 26, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 26, 2016
First Posted Date  ICMJE March 16, 2016
Results First Submitted Date  ICMJE June 6, 2019
Results First Posted Date  ICMJE June 26, 2019
Last Update Posted Date June 26, 2019
Actual Study Start Date  ICMJE March 2, 2016
Actual Primary Completion Date June 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2016)
  • WOMAC Pain subscale. [ Time Frame: 24 weeks. ]
    Change from Baseline to Week 24 in the WOMAC Pain subscale.
  • WOMAC Physical Function subscale [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the WOMAC Physical Function subscale.
  • Patient's Global Assessment of Osteoarthritis [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the Patient's Global Assessment of Osteoarthritis.
Change History Complete list of historical versions of study NCT02709486 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 16 ]
    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). 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) Pain Subscale at Week 32 [ Time Frame: Baseline, Week 32 ]
    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). 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 Weeks 2, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 16 ]
    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 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32 [ Time Frame: Baseline, Week 32 ]
    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 Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 16 ]
    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).
  • Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32 [ Time Frame: Baseline, Week 32 ]
    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 worse condition.
  • Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index [ Time Frame: Weeks 2, 4, 8, 12, 16, 24 and 32 ]
    Participants were considered as OMERACT-OARSI responders: if the change (improvement) from baseline to week of interest was greater than or equal to (>=) 50 percent and >= 2 units in either WOMAC pain subscale or physical function subscale score; if change (improvement) from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 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 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [extreme difficulty], higher score = worse physical function) and PGA of OA (score: 1 [very good] to 5 [very poor], higher score = worse condition). Missing data was imputed using mixed baseline/last observation carried forward (BOCF/LOCF).
  • 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 [ Time Frame: Baseline, Weeks 16 and 24 ]
    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a 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. Percentage of participants with cumulative reduction (as percent) (greater than 0% ; >= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in WOMAC pain subscale from Baseline to Weeks 16 and 24 were reported, participants (%) are reported more than once in categories specified. Missing data was imputed using mixed BOCF/LOCF.
  • Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response [ Time Frame: Week 2, 4, 8, 12, 16, 24 and 32 ]
    Percentage of participants with reduction in WOMAC pain intensity of at least (>=) 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16, 24 and 32 compared to baseline were classified as responders to WOMAC pain subscale and are reported here. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with 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 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. Missing data was imputed using mixed BOCF/LOCF.
  • Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response [ Time Frame: Weeks 2, 4, 8, 12, 16, 24 and 32 ]
    Percentage of participants with reduction in WOMAC physical function of at least (>=)30%,50%,70% and 90% at weeks 2,4,8,12,16,24 and 32 compared to baseline were classified as responders to WOMAC physical function subscale. 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:Participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee/hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.
  • 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 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Percentage of participants with cumulative reduction (as percent) (greater than 0 %; >= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 % and 90%; =100 %) in WOMAC physical function subscale from Baseline to Weeks 16 and 24 were reported. 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: participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale:17-item questionnaire to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), higher scores indicate extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.
  • Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis [ Time Frame: Weeks 2, 4, 8, 12, 16, 24 and 32 ]
    PGA of OA 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 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 worse condition. Percentage of participants with improvement of at least 2 points from Baseline in PGA of OA were reported. Missing data was imputed using mixed BOCF/LOCF.
  • 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 [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 ]
    Participants assessed their average pain in the index hip/knee in the past 24 hours using a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data represents averages of the values reported during the 8-week interval up to and including the given week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.
  • Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32 [ Time Frame: Baseline, Weeks 28 and 32 ]
    Participants assessed their average pain in the index hip/knee in the past 24 hours using a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data represents averages of the values reported during the 8-week interval up to and including the given week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16 and 24 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32 [ Time Frame: Baseline, Week 32 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on a NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16 and 24 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32 [ Time Frame: Baseline, Week 32 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.
  • 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 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16 and 24 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 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) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32 [ Time Frame: Baseline, Week 32 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 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) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16 and 24 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 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) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32 [ Time Frame: Baseline, Week 32 ]
    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
  • Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline [ Time Frame: Baseline ]
    WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
  • Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 [ Time Frame: Baseline, Weeks 8, 16 and 24 ]
    WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
  • European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score [ Time Frame: Baseline, Weeks 8, 16 and 24 ]
    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The health utility score for a participant with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a participant reports greater levels of problems across the five dimensions.
  • European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value [ Time Frame: Baseline, Weeks 8, 16 and 24 ]
    EQ-5D-5L: standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses from the five domains were used to calculate a single utility index (the Overall health utility score) where values are less than equal to (<=) 1. The Overall health utility score for a participant with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a participant reports greater levels of problems across the five dimensions.
  • 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? [ Time Frame: Weeks 16 and 24 ]
    The mPRTI is a self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction), participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. For participant satisfaction, participants responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where 1=extremely dissatisfied, 2=dissatisfied, 3=neither satisfied nor dissatisfied, 4=satisfied and 5=extremely satisfied. Higher scores indicated greater satisfaction.
  • 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? [ Time Frame: Weeks 16 and 24 ]
    The mPRTI is a self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction), participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess previous treatment, participants responded for, 1=injectable prescription medicines, 2=prescription medicines taken by mouth, 3=surgery, 4=prescription medicines and surgery and 5=no treatment.
  • 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? [ Time Frame: Weeks 16 and 24 ]
    The mPRTI is a self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction), participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess preference to continue using the investigational product, participants responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where, 1= yes, I definitely prefer the drug that I am receiving now, 2= I have a slight preference for the drug that I am receiving now, 3= I have no preference either way, 4= I have a slight preference for my previous treatment, 5= No, I definitely prefer my previous treatment. Higher scores indicate lesser preference to use the investigational product.
  • 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? [ Time Frame: Weeks 16 and 24 ]
    The mPRTI is a self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction), participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess Patient willingness to use drug again, participants responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where, 1= yes, I would definitely want to use the same drug again, 2= I might want to use the same drug again, 3= I am not sure, 4= I might not want to use the same drug again, 5= no, I definitely would not want to use the same drug again. Higher scores indicate lesser willingness to use the investigational product.
  • Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Visits of services directly related to osteoarthritis evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner.
  • Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of participants who visited the emergency room due to osteoarthritis.
  • Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of visits to the emergency room due to OA.
  • Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of participants who were hospitalized due to OA.
  • Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of nights stayed in the hospital due to OA.
  • Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of participants who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices.
  • Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage (during 3 months prior to baseline) at baseline, Week 32 and Week 48. Domain evaluated was number of participants who quit job due to OA.
  • Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis [ Time Frame: Baseline, Weeks 32 and 48 ]
    Osteoarthritis HCRU assessed healthcare usage (during 3 months prior to baseline) at baseline, Week 32 and Week 48. Domain evaluated was duration since quitting job due to OA.
  • Number of Participants Who Withdrew Due to Lack of Efficacy [ Time Frame: Baseline up to Week 24 ]
    Number of participants who withdrew from treatment due to lack of efficacy have been reported here.
  • Time to Discontinuation Due to Lack of Efficacy [ Time Frame: Baseline up to Week 24 ]
    Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of participant from treatment due to lack of efficacy.
  • Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24 ]
    In case of inadequate pain relief, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication between day 1 and week 24. Number of participants with any use of rescue medication during the particular study week were summarized.
  • Number of Participants Who Took Rescue Medication During Week 32 [ Time Frame: Week 32 ]
    In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of participants with any use of rescue medication during the 4 weeks up to and including the particular study week were summarized.
  • Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24 ]
    In case of inadequate pain relief during the treatment period, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week a could be taken as rescue medication. Number of days the participants used the rescue medication during the particular study weeks were summarized.
  • Number of Days of Rescue Medication Used at Week 32 [ Time Frame: Week 32 ]
    In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of days per week the participants used the rescue medication during the 4 weeks up to and including the particular study week were summarized.
  • Amount of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24 ]
    In case of inadequate pain relief, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication. The total dosage of acetaminophen in milligrams used during the specified week were summarized.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study [ Time Frame: Baseline up to Week 48 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 were events between first dose of study drug and up to week 48 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
  • Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study [ Time Frame: Baseline up to Week 48 ]
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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 were events between first dose of study drug and up to week 48 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
  • Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline [ Time Frame: Baseline up to Week 48 ]
    Primary Abnormality criteria: HGB, hematocrit, RBC count <0.8* lower limit of normal(LLN); Ery. mean corpuscular volume/hemoglobin/ HGB concentration, RBCs distribution width <0.9*LLN, >1.1*upper limit of normal(ULN); platelets <0.5*LLN,>1.75*ULN; WBC count<0.6*LLN, >1.5*ULN; Lymphocytes,Leukocytes,Neutrophils <0.8*LLN, >1.2*ULN; Basophils,Eosinophils,Monocytes>1.2*ULN; Prothrombin time/Intl. normalized ratio>1.1*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen,creatinine,Cholesterol,triglycerides >1.3*ULN; Urate>1.2*ULN; sodium<0.95*LLN,>1.05*ULN; potassium,chloride,calcium,magnesium,bicarbonate <0.9*LLN, >1.1*ULN; phosphate<0.8*LLN, >1.2*ULN; glucose<0.6*LLN, >1.5*ULN; HGB A1C >1.3*ULN; creatine kinase>2.0*ULN, specific gravity<1.003, >1.030; pH<4.5, >8; Urine Glucose, protein,HGB,bilirubin >=1; Ketones>=1;Urine erythrocytes,Leukocytes>=20.
  • Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline [ Time Frame: Baseline up to Week 48 ]
    Primary Abnormality criteria: hemoglobin; hematocrit; RBC count < 0.8*LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*ULN; platelets <0.5*LLN,>1.75*upper limit of normal (ULN); white blood cell count<0.6*LLN, >1.5*ULN; Lymphocytes, Leukocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils, Eosinophils, Monocytes >1.2*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides >1.3*ULN; Urate >1.2*ULN; sodium <0.95*LLN,>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate <0.9*LLN, >1.1*ULN; phosphate <0.8*LLN, >1.2*ULN; glucose <0.6*LLN, >1.5*ULN; Hemoglobin A1C >1.3*ULN; creatine kinase >2.0*ULN; Nitrite >=1.
  • Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48 ]
    Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP).
  • Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 [ Time Frame: Baseline, Weeks 2, 4, 8, 12,16, 24, 32 and 48 ]
    Heart rate was measured at sitting position.
  • Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    A 12-lead ECG was recorded after participants had rested for at least 5 minutes in the supine position in a quiet environment. All standard intervals (PR, QRS, QT, QTcF, QTcB, QTcF, RR intervals) were collected.
  • Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Heart rate was measured at sitting position.
  • Percentage of Participants With Adjudicated Joint Safety Outcomes [ Time Frame: Baseline up to Week 48 ]
    Incidence of participants with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive OA (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture.
  • Percentage of Participants With Total Joint Replacements [ Time Frame: Baseline up to Week 48 ]
    Percentage of participants who underwent at least one total knee, hip or shoulder joint replacement surgery.
  • Number of Participants With Confirmed Orthostatic Hypotension [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48 ]
    Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: For systolic BP <=150 mmHg (mean supine): Reduction in systolic BP>=20 mmHg or reduction in diastolic BP>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP >150 mmHg (mean supine): Reduction in systolic BP>=30 mmHg or reduction in diastolic BP>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.
  • Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24 [ Time Frame: Baseline, Week 24 ]
    The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total impact score was the sum of all symptom rating scores, with 0 assigned where the participant did not have the particular symptom. The range for the total impact score is 0-60 for males and 0-55 for females, higher scores indicating higher impact.
  • Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48 ]
    NIS is a standardized instrument used to evaluate participant for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, from both the left and right side, where 24 items scored from 0 (normal) to 4 (paralysis), higher score indicated higher abnormality/impairment and 13 items scored from 0 (normal), 1 (decreased) and 2 (absent), higher score indicated higher impairment. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased impairment.
  • Number of Participants With Anti Tanezumab Antibodies [ Time Frame: Baseline, Weeks 8,16, 24, 32 and 48 ]
    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Participants listed as having anti-tanezumab antibodies had ADA titer level >=3.32. Less than 3.32 was considered below the limit of quantitation.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2016)
  • WOMAC Pain subscale [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32. ]
    WOMAC Pain subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
  • WOMAC Physical Function subscale [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32 ]
    WOMAC Physical Function subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
  • Patient's Global Assessment of Osteoarthritis [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32. ]
    Patient's Global Assessment of Osteoarthritis (5 point Likert scale) change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
  • OMERACT OARSI responder index [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    OMERACT OARSI responder index at Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale [ Time Frame: Week 16 and 24 ]
    Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale score to Week 16 and 24 (endpoint for summary only).
  • Treatment Response: Reduction in the WOMAC Pain subscale of 30%, 50%, 70% and 90% [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    Treatment Response: Reduction in the WOMAC Pain subscale of 30%, 50%, 70% and 90%, at Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Treatment Response: Reduction in the WOMAC Physical Function subscale of 30%, 50%, 70% and 90% [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    Treatment Response: Reduction in the WOMAC Physical Function subscale of 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale [ Time Frame: Week 16 and 24 ]
    Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale score to Week 16 and 24 (endpoint for summary only).
  • Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Osteoarthritis [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Average pain score in the index knee or hip change [ Time Frame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32. ]
    Average pain score in the index knee or hip change from Baseline to Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32.
  • WOMAC Stiffness subscale change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24 and 32 ]
    WOMAC Stiffness subscale change from Baseline to Weeks 2, 4, 8, 12, 16, 24 and 32.
  • WOMAC Average change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    WOMAC Average score change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
  • WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
  • WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs, change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline [ Time Frame: Weeks 8, 16 and 24. ]
    Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline to Weeks 8, 16 and 24.
  • EQ 5D-5L Health State Utility and Five Items [ Time Frame: Weeks 8, 16 and 24. ]
    EQ 5D-5L Health State Utility and Five Items (Mobility; Self-Care; Usual Activities; Pain/Discomfort; Anxiety/Depression) change from Baseline to Weeks 8, 16 and 24.
  • Patient Reported Treatment Impact Assessment-Modified (mPRTI) [ Time Frame: Weeks 16 and 24. ]
    Patient Reported Treatment Impact Assessment-Modified (mPRTI) at Weeks 16 and 24.
  • Health Care Resource Utilization [ Time Frame: Weeks 32 and 48. ]
    Health Care Resource Utilization at Baseline, and Weeks 32 and 48.
  • Incidence of discontinuation due to Lack of Efficacy [ Time Frame: 24 weeks ]
    Incidence of discontinuation due to Lack of Efficacy.
  • Incidence of rescue medication use [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    Usage of rescue medication (incidence and number of days of use) during Weeks 2, 4, 8, 12, 16, 24, and 32.
  • Amount of rescue medication taken [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24. ]
    Usage of rescue medication (amount taken) during Weeks 2, 4, 8, 12, 16 and 24.
  • Incidence of Subjects with Adverse Events. [ Time Frame: 48 weeks ]
    Adverse Events.
  • Hematology testing [ Time Frame: Weeks 16 and 32. ]
    Hematology testing
  • Blood pressure [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Blood pressure in mmHg
  • Electrocardiogram [ Time Frame: Weeks 24 and 48. ]
    Electrocardiogram
  • Incidence of individual adjudication outcomes [ Time Frame: 48 weeks ]
    The Adjudication Committee will be asked to review all possible or probable joint related safety events, total joint replacement, as well as investigator reported adverse events of osteonecrosis, rapidly progressive osteoarthritis, subchondral insufficiency fracture (spontaneous osteonecrosis of the knee [SPONK]) or pathologic fracture.
  • Incidence of all cause total joint replacements [ Time Frame: 48 weeks ]
    All cause total joint replacement as defined in the protocol.
  • Orthostatic (supine / standing) blood pressure assessments. [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Orthostatic (supine / standing) blood pressure assessments.
  • Survey of Autonomic Symptom scores. [ Time Frame: Week 24. ]
    Survey of Autonomic Symptom scores.
  • Neurologic exam (Neuropathy Impairment Score [NIS]). [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32,and 48. ]
    Neurologic exam (Neuropathy Impairment Score [NIS]).
  • Anti-tanezumab antibody assessments. [ Time Frame: Weeks 8, 16, 24, 32 and 48. ]
    Anti-tanezumab antibody assessments.
  • Musculoskeletal examination. [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Physical examination of all major joints.
  • Time to discontinuation due to Lack of Efficacy. [ Time Frame: 24 weeks ]
    Time to discontinuation due to Lack of Efficacy.
  • Clinical chemistry testing [ Time Frame: Weeks 16 and 32. ]
    Clinical chemistry testing
  • General examination [ Time Frame: Week 24 ]
    General examination including cardiovascular, respiratory, abdominal and skin systems.
  • Heart rate [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Heart rate in beats per minutes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee.
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

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:

  1. tanezumab 2.5 mg;
  2. tanezumab 5 mg;
  3. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Osteoarthritis, Hip
  • Osteoarthritis, Knee
Intervention  ICMJE
  • Drug: Tanezumab
    2.5 mg
  • Drug: Tanezumab
    5 mg
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Low dose
    Investigational product
    Intervention: Drug: Tanezumab
  • Experimental: High dose
    Investigational product
    Intervention: Drug: Tanezumab
  • Placebo Comparator: Placebo
    Investigational product
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 5, 2018)
849
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2016)
810
Actual Study Completion Date  ICMJE November 14, 2018
Actual Primary Completion Date June 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Bulgaria,   Finland,   France,   Germany,   Hungary,   Italy,   Japan,   Poland,   Portugal,   Romania,   Slovakia,   Spain,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02709486
Other Study ID Numbers  ICMJE A4091057
2013-004508-21 ( EudraCT Number )
OA 6-MONTH EU STUDY ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP