Tanezumab In Osteoarthritis Of The Knee (2)

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

The purpose of this study is to test the efficacy and safety of 2 doses of tanezumab compared with naproxen and placebo in patients with osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Arthritis; Osteoarthritis
• Intervention / Treatment: Biological: tanezumab 10 mg; Biological: tanezumab 5 mg; Drug: naproxen; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 832
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Anniston Medical Clinic, PC
    • Anniston, Alabama, United States, 36207
      • Pinnaccle Research Group, LLC
  • Arizona
    • Mesa, Arizona, United States, 85203
      • Clinical Research Advantage, Inc. / Mesa Family Medical Center, PC
    • Paradise Valley, Arizona, United States, 85253
      • Arizona Arthritis & Rheumatology Associates, P.C.
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Centers
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85037
      • Arizona Arthritis & Rheumatology Associates, P.C.
    • Tucson, Arizona, United States, 85724
      • University of Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona - Arizona Arthritis Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • St. Joseph'S Mercy Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Osteoporosis Medical Center
    • Fresno, California, United States, 93720
      • Valley Research
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Thousand Oaks, California, United States, 91360
      • Lawrence P McAdam, MD / A Medical Corporation
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Delaware
    • Newark, Delaware, United States, 19713
      • Javed Rheumatology Associates, Inc.
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc.
    • Clearwater, Florida, United States, 33756
      • Innovative Research Of West Florida, Inc
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Longwood, Florida, United States, 32779
      • Adult Medicine Specialists
    • Longwood, Florida, United States, 32779
      • Genesis Research International
    • Miami, Florida, United States, 33175
      • Kendall South Medical Center, Inc
    • Palm Harbor, Florida, United States, 34684
      • The Arthritis Center
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tamarac, Florida, United States, 33321
      • West Broward Rheumatology Associates, Inc.
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Arthritis and Rheumatology of Georgia
    • Decatur, Georgia, United States, 30033
      • Jeffrey D. Lieberman, MD
    • Marietta, Georgia, United States, 30060
      • Marietta Rheumatology
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Internal Medicine
    • Woodstock, Georgia, United States, 30188
      • Physician Pain Care
  • Idaho
    • Boise, Idaho, United States, 83702
      • Sonora Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Rehabilitation Institute of Chicago
    • Morton, Illinois, United States, 61550
      • Koch Family Practice
    • Morton Grove, Illinois, United States, 60053
      • Illinois Bone and Joint Institute, LLC
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Center for Clinical Research
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • David H. Neustadt, PSC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70816
      • Stanocola Medical Center
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis and Osteoporosis Center of Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology, P.C.
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Medical Advanced Pain Specialists
    • Edina, Minnesota, United States, 55435
      • MAPS Applied Research Center, Inc
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium
    • Las Vegas, Nevada, United States, 89119
      • Mirkil Medical
    • Las Vegas, Nevada, United States, 89128
      • G. Timothy Kelly, MD
    • Las Vegas, Nevada, United States, 89128
      • Michael Clifford, MD
  • 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
    • New York, New York, United States, 10024
      • The Medical Research Network, LLC
    • Rochester, New York, United States, 14618
      • AAIR Research Center
    • Roslyn, New York, United States, 11576
      • Andrew J. Porges, MD, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Carolina Bone and Joint, PA
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Odyssey Research
    • Fargo, North Dakota, United States, 58104
      • Plains Medical Clinic, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45224
      • Hightop Medical Research Center
    • 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 Incorporated
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • West Reading, Pennsylvania, United States, 19611
      • Clinical Research Center of Reading, LLP
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Appalachian Medical Research, Inc
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Austin, Texas, United States, 78705
      • Capitol Medical Clinic
    • Austin, Texas, United States, 78705
      • Office of Walter F Chase, MD, PA
    • Dallas, Texas, United States, 75230
      • North Texas Joint Care, PA
    • Houston, Texas, United States, 77008
      • Asif Cochinwala, MD, PA
    • Houston, Texas, United States, 77036
      • Pioneer Research Solutions, Inc
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
    • San Antonio, Texas, United States, 78217
      • Radiant Research San Antonio Northeast
    • San Antonio, Texas, United States, 78229
      • Diagnostic Research Group
    • San Antonio, Texas, United States, 78229
      • South Texas Radiology Group
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research, LLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
    • Portsmouth, Virginia, United States, 23701
      • Arthritis and Rheumatic Diseases
  • Washington
    • Yakima, Washington, United States, 98902
      • Clinical Trials Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Osteoarthritis of the knee according to Kellgren-Lawrence x-ray grade of 2

Exclusion Criteria:

• Pregnancy or intent to become pregnant
• BMI greater than 39
• other severe pain, significant cardiac, neurologic or cardiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: tanezumab 10 mg; tanezumab 10 mg one dose at weeks 0 and 8
Experimental: 2	Biological: tanezumab 5 mg; tanezumab 5 mg one dose at weeks 0 and 8
Placebo Comparator: 4	Other: placebo; placebo to match tanezumab and naproxen dosing
Active Comparator: 3	Drug: naproxen; naproxen 1000 mg daily for 16 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 in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more 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 in participants with osteoarthritis of knee. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a numerical rating scale of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate more difficulty. An overall possible WOMAC physical function subscale score range is of 0 (minimum difficulty) to 10 (maximum 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 of Osteoarthritis at Week 16: Baseline Observation Carried Forward (BOCF)	Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse 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 and 12: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.	Baseline, Week 2, 4, 8, 12
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.	Baseline, Week 2, 4, 8, 12
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a numerical rating scale of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate more difficulty. An overall possible WOMAC physical function subscale score range is of 0 (minimum difficulty) to 10 (maximum 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
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a numerical rating scale of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate more difficulty. An overall possible WOMAC physical function subscale score range is of 0 (minimum difficulty) to 10 (maximum 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
Change From Baseline in Patient Global Assessment of Osteoarthritis at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)	Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition.	Baseline, Week 2, 4, 8, 12
Change From Baseline in Patient Global Assessment of Osteoarthritis at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)	Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition.	Baseline, Week 2, 4, 8, 12
Percentage of Responders For Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI): Baseline Observation Carried Forward (BOCF)	A participant was considered as an OMERACT-OARSI responder: if the improvement from baseline to week of interest was greater than or equal to (>=) 50 percent and >=2 units in WOMAC pain or physical function subscale; if improvement from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: a) WOMAC pain subscale, b) WOMAC physical function subscale, c) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [minimum pain] to 10 [maximum pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = higher difficulty) and PGA of osteoarthritis (score: 1 [minimum affected] to 5 [maximum affected], higher score = worse condition). Percentage of participants who were OMERACT-OARSI responder were reported in this outcome measure.	Weeks 2, 4, 8, 12, 16
Percentage of Responders For Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI): Last Observation Carried Forward (LOCF)	A participant was considered as an OMERACT-OARSI responder: if the improvement from baseline to week of interest was greater than or equal to (>=) 50 percent and >=2 units in WOMAC pain or physical function subscale; if improvement from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: a) WOMAC pain subscale, b) WOMAC physical function subscale, c) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [minimum pain] to 10 [maximum pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = higher difficulty) and PGA of osteoarthritis (score: 1 [minimum affected] to 5 [maximum affected], higher score = worse condition). Percentage of participants who were OMERACT-OARSI responder were reported in this outcome measure.	Week 2, 4, 8, 12, 16
Percentage of Participants With at Least 30 Percent, and 50 Percent Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale were reported in this outcome measure.	Week 2, 4, 8, 12, 16
Percentage of Participants With at Least 30 Percent, and 50 Percent Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale were reported in this outcome measure.	Week 2, 4, 8, 12, 16
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 the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition. Percentage of participants with at least 2 points improvement from baseline in PGA of osteoarthritis at specified weeks were reported.	Baseline, Week 2, 4, 8, 12, 16
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 the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition. Percentage of participants with at least 2 points improvement from baseline in PGA of osteoarthritis at specified weeks were reported.	Baseline, Week 2, 4, 8, 12, 16
Percentage of Participants With Cumulative Reduction From Baseline up to Week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with cumulative reduction (greater than 0 percent [%]; >= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 % and 90%; = 100 %) in WOMAC pain subscale from Baseline up to Week 16 were reported.	Baseline up to Week 16
Percentage of Participants With Cumulative Reduction From Baseline up to Week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with cumulative reduction (greater than 0 percent [%]; >= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 % and 90%; = 100 %) in WOMAC pain subscale from Baseline up to Week 16 were reported.	Baseline up to Week 16
Change From Baseline for the Average Pain Score in the Index Knee at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	Participants assessed daily average pain score in the index knee using a scale ranging from 0 (no pain) to 10 (maximum pain), where higher scores indicate more pain. A weekly mean was calculated using the daily average index knee pain scores within each specified study week.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline for the Average Pain Score in the Index Knee at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)	Participants assessed daily average pain score in the index knee using a scale ranging from 0 (no pain) to 10 (maximum pain), where higher scores indicate more pain. A weekly mean was calculated using the daily average index knee pain scores within each specified study week.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in knee joint during past 48 hours. It is calculated as mean of the scores from 2 individual questions each scored on numerical rating scale of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate greater stiffness. An overall possible WOMAC stiffness subscale score range is of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in moving the index knee.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in knee joint during past 48 hours. It is calculated as mean of the scores from 2 individual questions each scored on numerical rating scale of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate greater stiffness. An overall possible WOMAC stiffness subscale score range is of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in moving the index knee.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale assess amount of pain experienced (score: 0 [minimum pain] to 10 [maximum pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = higher difficulty) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [minimum stiffness] to 10 [maximum stiffness], higher score = higher stiffness). WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores, giving an overall possible WOMAC average score range of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse response.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale assess amount of pain experienced (score: 0 [minimum pain] to 10 [maximum pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = higher difficulty) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [minimum stiffness] to 10 [maximum stiffness], higher score = higher stiffness). WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores, giving an overall possible WOMAC average score range of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse response.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Walking on a Flat Surface at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when walking on a flat surface, where 0= no pain and 10= extreme pain. Higher score indicates more pain.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Walking on a Flat Surface at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when walking on a flat surface, where 0= no pain and 10= extreme pain. Higher score indicates more pain.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Going Up or Down Stairs at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when going up or down stairs, where 0= no pain and 10= extreme pain. Higher score indicates more pain.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Going Up or Down Stairs at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when going up or down stairs, where 0= no pain and 10= extreme pain. Higher score indicates more pain.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Short-Form 36 Health Survey (SF-36) 8 Health Domains, Mental Component Aggregate and Physical Component Aggregate Scores at Week 12 and 16: Baseline Observation Carried Forward (BOCF)	SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional and domain 8= mental health. Total score for each of the 8 domains are scaled from 0 (minimum level of functioning) to 100 (maximum level of functioning). These 8 domains are also summarized as 2 summary scores: mental component aggregate (MCA) and physical component aggregate (PCA). Total score range for each of the 2 summary scores =0 (minimum level of functioning) to 100 (maximum level of functioning). Higher (8 domains and 2 summary) scores indicate a better health related quality of life.	Baseline, Week 12, 16
Change From Baseline in Short-Form 36 Health Survey (SF-36) 8 Health Domains, Mental Component Aggregate and Physical Component Aggregate Scores at Week 12 and 16: Last Observation Carried Forward (LOCF)	SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional and domain 8= mental health. Total score for each of the 8 domains are scaled from 0 (minimum level of functioning) to 100 (maximum level of functioning). These 8 domains are also summarized as 2 summary scores: mental component aggregate (MCA) and physical component aggregate (PCA). Total score range for each of the 2 summary scores =0 (minimum level of functioning) to 100 (maximum level of functioning). Higher (8 domains and 2 summary) scores indicate a better health related quality of life.	Baseline, Week 12, 16
Percentage of Participants Who Used Rescue Medication	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days in a week could be taken as rescue medication. Percentage of participants with any use of rescue medication during the specified study week were summarized.	Week 2, 4, 8, 12, 16
Number of Days Participants Used Rescue Medication	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days in a week could be taken as rescue medication. Number of days participants used any of the rescue medication, during the specified week were summarized.	Week 2, 4, 8, 12, 16
Amount of Rescue Medication Taken	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days in a week could be taken as rescue medication. The total dosage of acetaminophen in mg used during the specified week were summarized.	Week 2, 4, 8, 12, 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 24 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.	Day 1 (Baseline) up to Week 24
Number of Participants With Laboratory Test Abnormalities	Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(<)0.8*lower limit of normal(LLN),MCV,MCH,MCHC<0.9*LLN or >1.1*ULN,platelet:<0.5*LLN or >1.75*upper limit of normal(ULN),white blood cell(WBC):<0.6*LLN or >1.5*ULN,lymphocyte,neutrophil,total neutrophil:<0.8*LLN or>1.2*ULN,basophil,eosinophil,monocyte:>1.2*ULN;total,direct bilirubin>1.5*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,LDH,alkaline phosphatase:> 3.0*ULN,total protein,albumin:<0.8*LLN or >1.2*ULN;blood urea nitrogen,creatinine:>1.3*ULN,uric acid>1.2*ULN;cholesterol,triglycerides>1.3*ULN;sodium <0.95*LLN or >1.05*ULN,potassium,chloride,calcium,magnesium,bicarbonate:<0.9*LLN or >1.1*ULN,phosphate<0.8*LLN or>1.2*ULN;glucose <0.6*LLN or >1.5*ULN,glycosylated Hgb >1.3*ULN,creatine kinase>2.0*ULN;urine(specific gravity <1.003or>1.030,pH <4.5or>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals>=1,RBC,WBC >1.5*ULN,epithelial cell>=6,casts,hyaline cast>1,bacteria>20).	Day 1 (Baseline) up to Week 24
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities	Criteria for potential clinical concern in ECG parameters are: Criterion 1= maximum QTcB interval (Bazett's correction) in range of 450 millisecond (msec) to less than 480 msec, Criterion 2= maximum QTcB interval in range of 480 msec to less than 500 msec, Criterion 3= maximum QTcB interval >= 500 msec; Criterion 4= maximum QTcF interval (Fridericia's correction) in range of 450 msec to less than 480 msec, Criterion 5= maximum QTcF interval in range of 480 msec to less than 500 msec, Criterion 6= maximum QTcF interval >= 500 msec, Criterion 7= maximum QTcB interval increase from baseline in range of 30 msec to less than 60 msec, Criterion 8= maximum QTcB interval increase >=60 msec, Criterion 9= maximum QTcF interval increase from baseline in range of 30 msec to less than 60 msec, Criterion 10= maximum QTcF interval increase >=60 msec.	Day 1 (Baseline) up to Week 24
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 2, 4, 8, 12, 16 and 24	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 function) to 4 (extreme abnormal function), higher score indicates higher abnormality and 13 items scored from 0 (normal function) to 2 (extreme abnormal function), higher score indicates higher abnormality. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicate increased impairment.	Baseline, Week 2, 4, 8, 12, 16, 24
Number of Participants With Positive Anti-Drug Antibody (ADA) Level	Participants who developed anti-tanezumab antibodies after treatment were evaluated for the presence of anti-tanezumab neutralizing antibodies in their serum. Number of participants with positive ADA were summarized for reporting groups: tanezumab 5 mg + placebo and tanezumab 10 mg + placebo. Results with titer value >= 4.32 nanogram per milliliter of anti-tanezumab neutralizing antibodies were counted as positive.	Baseline, Week 8, 16, 24
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities	Assessment of the clinical significance of vital sign changes was done per investigator judgment. Changes in vital signs determined to be clinically significant by the investigator were reported as adverse events.	Day 1 (Baseline) up to Week 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.
• Ekman EF, Gimbel JS, Bello AE, Smith MD, Keller DS, Annis KM, Brown MT, West CR, Verburg KM. Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen. J Rheumatol. 2014 Nov;41(11):2249-59. doi: 10.3899/jrheum.131294. Epub 2014 Oct 1.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2009
• Primary Completion (Actual): May 17, 2010
• Study Completion (Actual): August 31, 2010

Study Registration Dates

• First Submitted: January 23, 2009
• First Submitted That Met QC Criteria: January 26, 2009
• First Posted (Estimate): January 27, 2009

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: April 20, 2021
• Last Verified: April 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; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Tanezumab; Naproxen
• Other Study ID Numbers: A4091015; P3 OA KNEE NSAID POPULATION (Other Identifier: 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.