Tanezumab in Osteoarthritis of the Knee

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

Test the efficacy and safety of 3 doses in Osteoarthritis of the knee in patients.

Study Overview

• Status: Completed
• Conditions: Arthritis; Osteoarthritis
• Intervention / Treatment: Biological: tanezumab; Biological: tanezumab; Biological: tanezumab; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 697
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center, Inc.
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Clinical Research Center of Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Delaware
    • Newark, Delaware, United States, 19713
      • Javed Rheumatology Associates, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research Of West Florida, Inc.
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research
    • DeLand, Florida, United States, 32720
      • Avail Clinical Rearch, LLC
    • Delray Beach, Florida, United States, 33484
      • Delray Research Associates
    • Delray Beach, Florida, United States, 33484
      • Arthritis Associates of South Florida, Clinical Research Center
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic, LLC
    • Miami, Florida, United States, 33186
      • South Medical Research Group
    • Miami, Florida, United States, 33126
      • Neurorehabilitation & Diagnostic Services
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Palm Harbor, Florida, United States, 34684
      • The Arthritis Center
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research Incorporated
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Centers
    • Port Orange, Florida, United States, 32127
      • AvivoClin Clinical Services
    • Saint Petersburg, Florida, United States, 33713
      • Dale G. Bramlet, MD, P.L
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Laureate Clinical Reseach Group
    • Decatur, Georgia, United States, 30033
      • Jefrey D. Lieberman, MD, PC
    • Fort Valley, Georgia, United States, 31030
      • Early Family Practice Center
    • Marietta, Georgia, United States, 30060
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Internal Medicine
  • Idaho
    • Boise, Idaho, United States, 83702
      • Sonora Clinical Research
  • Illinois
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
  • Indiana
    • South Bend, Indiana, United States, 46601-1071
      • Memorial Health System, Inc./ Michiana Arthritis & Osteoporosis Center
    • South Bend, Indiana, United States, 46601
      • Memorial Health System, Inc.
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Center for Clinical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Arthritis Center of Lexington
    • Lexington, Kentucky, United States, 40515
      • Bluegrass Community Research, Inc
    • Louisville, Kentucky, United States, 40202
      • David H. Neustadt P.S.C.
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Gulf Coast Research, LLC
    • Baton Rouge, Louisiana, United States, 70808
      • The Baton Rouge Clinic
    • Monroe, Louisiana, United States, 71203
      • Arthritis and Diabetes Clinic
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • Office of Peter A. Holt, MD
    • Frederick, Maryland, United States, 21702
      • The Arthritis and Osteoporosis Center of Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Mansfield, Massachusetts, United States, 02048
      • Mansfield Health Center
    • Peabody, Massachusetts, United States, 01960-1628
      • Arthritis Associates Inc.
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Ann Arbor Clinical Research
    • Saint Clair Shores, Michigan, United States, 48081
      • KMED Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • MAPS Applied Research Center
    • Edina, Minnesota, United States, 55435
      • Medical Advanced Pain Specialists
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center, Incorporated
  • New York
    • Elmira, New York, United States, 14901
      • Health Sciences Research Center at Asthma & Allergy Assoc., PC
    • Ithaca, New York, United States, 14850
      • Health Sciences Research Center at Asthma and Allergy Associates P.C.
    • New York, New York, United States, 10128
      • The Medical Research Network, LLC
    • Plainview, New York, United States, 11803
      • Prem C. Chatpar, MD, LLC
    • Rochester, New York, United States, 14618
      • AAIR Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207-1198
      • Arthristis and Osteoporosis Consultants of the Carolinas
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Raleigh, North Carolina, United States, 27609
      • C.A.R.E. Center
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45224
      • Hilltop Physicians Inc, Hightop Medical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • Southwest Rheumatology and Research Group, LLC
    • Zanesville, Ohio, United States, 43701
      • Pharmacotherapy Research Associates,Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
  • Oregon
    • Beaverton, Oregon, United States, 97008
      • EPIC Imaging West
    • Portland, Oregon, United States, 97239
      • Covance Cru, Inc.
    • Portland, Oregon, United States, 97220
      • EPIC Imaging East:
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, Pc
    • Downingtown, Pennsylvania, United States, 19335-2620
      • Brandywine Clinical Research
    • Duncansville, Pennsylvania, United States, 16635-0909
      • Altoona Center for Clinical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Johnson City, Tennessee, United States, 37604-1417
      • Appalachian Medical Research
  • Texas
    • Austin, Texas, United States, 78705
      • Walter Chase, MD
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • San Antonio, Texas, United States, 78217
      • Texas Arthritis Research Center, PA
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
    • San Antonio, Texas, United States, 78217
      • Radiant Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
  • Washington
    • Yakima, Washington, United States, 98902
      • Clinical Trials Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Osteoarthritis of the knee according to ACR criteria with a 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 knee injections arthroplasty or replace 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 or intent to become pregnant during the study
• BMI greater than 39
• other severe pain, significant cardiac, neurological or psychological conditions, or above the protocol limits for laboratory and blood pressure results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Biological: Placebo; IV placebo to match tanezumab at 1 dose every 8 weeks
EXPERIMENTAL: Tanezumab 10 mg	Biological: tanezumab; IV tanezumab 10 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 5 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 2.5 mg at 1 dose every 8 weeks
EXPERIMENTAL: Tanezumab 5 mg	Biological: tanezumab; IV tanezumab 10 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 5 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 2.5 mg at 1 dose every 8 weeks
EXPERIMENTAL: Tanezumab 2.5 mg	Biological: tanezumab; IV tanezumab 10 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 5 mg at 1 dose every 8 weeks; Biological: tanezumab; IV tanezumab 2.5 mg at 1 dose every 8 weeks

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 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 (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.	Baseline (Day 1), Week 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale 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 OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), 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 knee 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.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 2, 4, 8, 12, 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.	Baseline, Week 2, 4, 8, 12, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 2, 4, 8, 12, 16, 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.	Baseline, Week 2, 4, 8, 12, 16, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8, 12, 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 OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), 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, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8, 12, 16, 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 OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), 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 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscales at Week 2, 4, 8, 12, 16, 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 OA. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 2 individual questions scored on NRS of (no stiffness) to 10 (extreme stiffness), with higher scores indicate higher stiffness. Total score range for WOMAC stiffness subscale score is (no stiffness) to 10 (extreme stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of knee.	Baseline, Week 2, 4, 8, 12, 16, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 2, 4, 8, 12, 16, 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 OA. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 2 individual questions scored on NRS of (no stiffness) to 10 (extreme stiffness), with higher scores indicate higher stiffness. Total score range for WOMAC stiffness subscale score is (no stiffness) to 10 (extreme stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of knee.	Baseline, Week 2, 4, 8, 12, 16, 24
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8, 12, 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 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.	Baseline, Week 2, 4, 8, 12, 24
Change 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 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.	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)	OMERACT-OARSI response: greater than or equal to (>=) 50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at Week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at Week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0-10, 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)	OMERACT-OARSI response: >= 50% improvement from baseline and absolute change from baseline of >=2 units at Week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at Week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0-10, higher score=higher pain/difficulty).	Week 2, 4, 8, 12, 16, 24
Percentage of Participants With at Least 30% and 50% Reduction From Baseline in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale Score: 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.	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 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.	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: 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 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.	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: 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 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.	Baseline, Week 2, 4, 8, 12, 16, 24
Percentage of Participants With Cumulative Reduction From Baseline to Week 16 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale Score: 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline up to Week 16 are reported.	Baseline up to Week 16
Percentage of Participants With Cumulative Reduction From Baseline to Week 16 in Western Ontario and McMaster 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 OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), 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 up to Week 16 are reported.	Baseline up to Week 16
Change From Baseline in Average Pain Score in the Index Knee at Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24: Baseline Observation Carried Forward (BOCF)	Participants assessed daily average knee pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Baseline score was calculated as the mean of the scores over the 3 days and a weekly mean was calculated using the daily pain scores within each study week. The change from Baseline was calculated using difference between each post-baseline weekly mean and the Baseline mean score.	Baseline, Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 12, 16, 24: Baseline Observation Carried Forward (BOCF)	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 knee. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, 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 at Week 2, 4, 8, 12, 16, 24: Baseline Observation Carried Forward (BOCF)	Participants answered, Question (Q)1: "How much pain have you had when walking on a flat surface?" and Q2: "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 = extreme 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, 24: Baseline Observation Carried Forward (BOCF)	SF-36v2: standardized survey evaluating 8 domains of functional health and wellbeing (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each domain were scaled 0 (poor health) to 100 (best health), higher scores indicating good health condition.	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, 24: Baseline Observation Carried Forward (BOCF)	SF-36v2: standardized survey evaluating 8 domains of functional health and wellbeing (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each domain were scaled 0 (poor health) to 100 (best health), higher scores indicating good health condition. For obtaining physical and mental component scores, z-score for each scale = (observed score - mean score for general 1990 United States [US] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score [better functioning])/lower (in case of negative z-score [worse functioning]) participant's value was relative to the mean of the reference population.	Baseline, Week 12, 24
Percentage of Participants Who Used Rescue Medications	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.	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.	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.	Week 2, 4, 8, 12, 16, 24

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Tive L, Bello AE, Radin D, Schnitzer TJ, Nguyen H, Brown MT, West CR. Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip. J Pain Res. 2019 Mar 19;12:975-995. doi: 10.2147/JPR.S191297. eCollection 2019. Erratum In: J Pain Res. 2020 Sep 14;13:2267-2268.
• Hochberg MC, Tive LA, Abramson SB, Vignon E, Verburg KM, West CR, Smith MD, Hungerford DS. When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious Adverse Joint Events in the Tanezumab Clinical Development Program. Arthritis Rheumatol. 2016 Feb;68(2):382-91. doi: 10.1002/art.39492.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2008
• Primary Completion (ACTUAL): August 24, 2009
• Study Completion (ACTUAL): January 14, 2010

Study Registration Dates

• First Submitted: August 11, 2008
• First Submitted That Met QC Criteria: August 12, 2008
• First Posted (ESTIMATE): August 13, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: pain; monoclonal antibody; nerve growth factor; OA; RN624; PF-04383119; anti-nerve growth factor
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tanezumab
• Other Study ID Numbers: A4091011; P3 OA KNEE (OTHER: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.