Analgesic Efficacy And Safety of Tanezumab Added On To Diclofenac SR In Patients With Osteoarthritis Of The Knee Or Hip

A PHASE 3, RANDOMIZED, DOUBLE BLIND, CONTROLLED, MULTI CENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ADDED ON TO DICLOFENAC SR IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP

The purpose of this study is to investigate the analgesic efficacy and safety of tanezumab added on to diclofenac SR in patients with osteoarthritis of the knee or hip currently experiencing partial benefit from, and are tolerating, diclofenac 150 mg/day therapy.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: tanezumab; Drug: diclofenac; Biological: tanezumab; Biological: tanezumab; Other: IV placebo

Detailed Description

This study was terminated on 16 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.

• Study Type: Interventional
• Enrollment (Actual): 607
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8036
    • LKH-Medizinische Universitatsklinik Graz
  • Senftenberg, Austria, 3541
    • Nuhr Zentrum
  • Wien, Austria, A-1090
    • ClinPharm International GmbH
  • Wien, Austria, A-1090
    • Medizinische Universitaet Wien/AKH
  • Wien, Austria, A-1100
    • Rheuma Zentrum Favoriten
• France
  • Nantes cedex 1, France, 44093
    • CHU de Nantes
  • Paris, France, 75010
    • Hopital Lariboisiere
• Germany
  • Berlin, Germany, 13125
    • Klinische Forschung Berlin-Buch GmbH
  • Berlin, Germany, 10117
    • Charite-Universitaetsmedizin Berlin
  • Berlin, Germany, 13353
    • Apotheke
  • Berlin-Buch, Germany, 13125
    • Viereck-Apotheke
  • Bochum, Germany, 44787
    • Herz Apotheke
  • Bochum, Germany, 44787
    • Synexus ClinPharm GmbH
  • Dresden, Germany, 01067
    • Synexus ClinParm GmbH
  • Dresden, Germany, 01127
    • Apotheke im Arztehaus Mickten
  • Goeppingen, Germany, 73033
    • Schiller Apotheke & Stadt Apotheke
  • Goeppingen, Germany, 73033
    • Schmerz- und Palliativzentrum Goeppingen
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH
  • Hamburg, Germany, 20253
    • Falken Apotheke Hoheluft
  • Hannover, Germany, 30159
    • Klinische Forschung Hannover - Mitte GmbH
  • Hannover, Germany, 30159
    • Loewen-Apotheke
  • Leipzig, Germany, 04315
    • Arkana Apotheke OHG
  • Leipzig, Germany, 04103
    • Synexus ClinPharm GmbH
  • Magdeburg, Germany, 39104
    • Synexus ClinPharm GmbH
  • Magdeburg, Germany, 39112
    • Apotheke im MSZ
  • Potsdam, Germany, 14467
    • Apotheke des Ernst von Bergmann Klinikums
  • Potsdam, Germany, 14467
    • Synexus ClinParm GmbH
  • Potsdam, Germany, 14480
    • Kirchsteig Apotheke
• Poland
  • Chelm Slaski, Poland, 41-403
    • "Centrum Medyczne MEDENS S.C. Niepubliczny Zaklad
  • Krakow, Poland, 31-510
    • Malopolskie Centrum Medyczne s.c.
  • Warszawa, Poland, 02-256
    • Centrum Medyczne OSTEOMED Sp. z o. o.
  • Wroclaw, Poland, 50-088
    • Synexus SCM Sp. z o.o.
  • Zgierz, Poland, 95-100
    • Niepubliczny Zaklad Opieki Zdrowotnej "POLIMEDICA"
• Romania
  • Bucharest, Romania, 010225
    • Clinical Emergency Military Hospital "Dr. Carol Davila"
  • Bucharest, Romania, 010584
    • Duo Medical srl
  • Bucharest, Romania, 011025
    • Medical Center "SANA"
  • Bucharest, Romania, 011172
    • Clinical Hospital "Sf. Maria"
  • Bucharest, Romania, 020985
    • Center of Rheumatology "Dr Ion Stoia"
  • Constanta, Romania, 900591
    • Clinical Emergency County Hospital Constanta
  • Galati, Romania, 800578
    • County Emergency Clinic Hospital "Sf. Apostol Andrei"
  • District Prahova
    • Ploiesti, District Prahova, Romania, 100337
      • Municipal Hospital No. 1 "Schuller"
• Russian Federation
  • Arkhangelsk, Russian Federation, 163000
    • Center polyclinic of Federal State Institution
  • Moscow, Russian Federation, 111539
    • State Healthcare Institution of Moscow city "City Clinical Hospital #15 n.a. O. M. Filatov"
  • Ryazan, Russian Federation, 390026
    • Chair of Hospital Therapy of Ryazan State Medical University
  • St. Petersburg, Russian Federation, 190068
    • St. Petersburg State Healthcare Institution "City Hospital #25 City Rheumatology Center"
  • St. Petersburg, Russian Federation, 191015
    • State Educational Institution of Additional Professional Education
  • St. Petersburg, Russian Federation, 194017
    • Institution of Russian Academy of Sciences "St. Petersburg Clinical Hospital of RAS"
  • St. Petersburg, Russian Federation, 196211
    • St. Petersburg State Healthcare Institution "City Outpatient Clinical #51"
  • St. Petersburg, Russian Federation, 199106
    • St. Petersburg State Healthcare Institution "City Pokrovskaya Hospital"
• Spain
  • Elda Alicante, Spain, 03600
    • Hospital Comarcal de Elda
  • Getafe-Madrid, Spain, 28905
    • Hospital Universitario Getafe
  • Madrid, Spain, 28007
    • Hospital G. U. Gregorio Maranon
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico Universitario Santiago
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15705
      • Hospital Nuestra Señora de La Esperanza
  • Alicante
    • Petrer, Alicante, Spain, 03610
      • Centro Salud Petrer 1
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Sweden
  • Goteborg, Sweden, 400 14
    • Me3plus AB
  • Goteborg, Sweden, 412 63
    • Me3plus AB
  • Malmo, Sweden, 211 52
    • Center for Lakemedelsstudier
  • Norrkoping, Sweden, 602 32
    • Medicinskt Centrum
• Ukraine
  • Chernivtsi, Ukraine, 58000
    • Chernivtsi Regional Clinical Hospital,Department of Rheumatology
  • Dnipropetrovsk, Ukraine, 49008
    • Road Clinical Hospital at Dnipropetrovsk station, Department of Rheumatology
  • Donetsk, Ukraine, 83045
    • Institute of Urgent and Recovery Surgery named after V.K. Gusaka AMS Ukraine
  • Donetsk, Ukraine, 83114
    • Central City Clinical Hospital#1, Department of Therapy,
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Clinical Hospital
  • Kharkiv, Ukraine, 61176
    • City Clinical Hospital #8, Department of reumatology,
  • Kiev, Ukraine, 04114
    • State Institution "Institute of Gerontology AMS of Ukraine"
  • Kyiv, Ukraine, 01023
    • Oleksandrivska Clinical Hospital in Kyiv-Department of Rheumatology # 1
  • Kyiv, Ukraine, 04053
    • Kyiv Central Basin Clinical Hospital, Department of cardiology,
  • Lviv, Ukraine, 79011
    • 4th City Communal Clinical Hospital, Department of Rheumatology,
  • Lviv, Ukraine, 79013
    • City communal clinical hospital #5, Dept. of Therapy, Danylo Galytskiy Lviv National Med. University
  • Ternopil, Ukraine, 46001
    • Communal Institution Ternopil regional council, "Ternopil Regional Clinical Hospital"
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya regional clinical hospital named after M.I. Pyrogova
  • Zaporizhzhia, Ukraine, 69118
    • Communal institution "City Hospital #7", Department of Therapy,
• United Kingdom
  • Dudley, West Midlands, United Kingdom, DY1 2HQ
    • Department of rheumatology
  • Wigan, United Kingdom, WN6 9EP
    • Wrightington Hospital
  • South Yorkshire
    • Barnsley, South Yorkshire, United Kingdom, S75 2EP
      • Barnsley Hospital NHS Trust

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 or hip according to ACR criteria with Kellgren-Lawrence X-ray grade equal to, or greater than, 2.
• Patients must be experiencing some benefit from their current stable dose regimen of oral diclofenac 150 mg/day and be tolerating their diclofenac regimen.
• Pain and function levels as required by the protocol at Screening and Baseline.
• Willing to discontinue all non-study pain medications throughout the study except as permitted per protocol.
• Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

• Pregnant women.
• BMI greater than 39.
• History of other disease that may involve index knee or hip including inflammatory joint diseases, chrystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis (RA), joint infections, neuropathic disorders, avascular necrosis, Paget's disease or tumors.
• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with OA.
• Signs and symptoms of clinically significant cardiac disease within 6 months prior to screening.
• Diagnosis or TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
• History, diagnosis , signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
• At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 150 micro-mol/L in men or 133 micro-mol/L in women.
• Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to Screening.
• Known hypersensitivity to NSAIDs (eg, diclofenac), cyclooxygenase inhibitors or paracetamol (acetaminophen).

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: Tanezumab 10 mg + diclofenac; IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)	Biological: tanezumab; IV tanezumab 10 mg every 8 weeks (through Week 16); Drug: diclofenac; Oral diclofenac SR 75 mg BID for 32 weeks; Biological: tanezumab; IV tanezumab 5 mg every 8 weeks (through Week 16); Biological: tanezumab; IV tanezumab 2.5 mg every 8 weeks (through Week 16)
Experimental: Tanezumab 5 mg + diclofenac; IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)	Biological: tanezumab; IV tanezumab 10 mg every 8 weeks (through Week 16); Drug: diclofenac; Oral diclofenac SR 75 mg BID for 32 weeks; Biological: tanezumab; IV tanezumab 5 mg every 8 weeks (through Week 16); Biological: tanezumab; IV tanezumab 2.5 mg every 8 weeks (through Week 16)
Experimental: Tanezumab 2.5 mg + diclofenac; IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)	Biological: tanezumab; IV tanezumab 10 mg every 8 weeks (through Week 16); Drug: diclofenac; Oral diclofenac SR 75 mg BID for 32 weeks; Biological: tanezumab; IV tanezumab 5 mg every 8 weeks (through Week 16); Biological: tanezumab; IV tanezumab 2.5 mg every 8 weeks (through Week 16)
Placebo Comparator: IV placebo + diclofenac; IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)	Drug: diclofenac; Oral diclofenac SR 75 mg BID for 32 weeks; Other: IV placebo; IV placebo to match tanezumab every 8 weeks (through Week 16)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16	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 or hip 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 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16	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 or hip 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 Score at Week 16	Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24	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 or hip 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, Weeks 2, 4, 8, 12, and 24
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12, 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. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip 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, Weeks 2, 4, 8, 12, and 24
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Weeks 2, 4, 8, 12, and 24	Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.	Baseline, Weeks 2, 4, 8, 12, and 24
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response; LOCF	OMERACT-OARSI responder: participant has >=50 percent (%) change and >=2 absolute change from Baseline in either WOMAC pain or physical function subscale scores or at least 2 of the following being true: >=20% change and >=1 absolute change from Baseline in WOMAC pain subscale; >=20% change and >=1 absolute change from Baseline in the WOMAC physical function subscale; >=20% change and >=1 absolute change from Baseline in PGA of osteoarthritis. WOMAC pain and physical function score: 0 to 10 with higher score = worse response. PGA score: 1 = very good and 5 = very poor.	Weeks 2, 4, 8, 12, 16, and 24
Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 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 osteoarthritis (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip 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. Greater percentage reduction indicates greater improvement. 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.	Baseline, Week 16 and 24
Percentage of Participants With At Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score; LOCF	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 or hip 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. Greater percentage reduction indicates greater improvement. 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.	Baseline, Weeks 2, 4, 8, 12, 16, and 24
Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; LOCF	Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition. A decrease of at least 2 points on the 5-point scale relative to baseline value indicated improvement.	Weeks 2, 4, 8, 12, 16, and 24
Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; Baseline Observation Carried Forward (BOCF)	Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition. A decrease of at least 2 points on the 5-point scale relative to baseline value indicates improvement.	Weeks 2, 4, 8, 12, 16, and 24
Change From Baseline in Average Pain Score in the Index Knee or Hip at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24	Participants were asked to assess index joint (knee/hip) pain during the past 24 hours on an 0-10 point integer scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline score was calculated as the mean of the scores in the index joint over the 3 days days in the initial pain assessment period and a weekly mean was calculated using the daily pain scores in the index joint within each study week. The change from Baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score, where negative change indicated an improvement.	Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at 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. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in index knee or hip 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/hip. Negative change indicated an improvement.	Baseline, Weeks 2, 4, 8, 12, 16, and 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16, and 24	WOMAC Index: 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 the hip and/or knee. WOMAC average score is the mean of the WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, with higher score indicating worse response. Greater reduction in WOMAC average score indicated greater improvement.	Baseline, Weeks 2, 4, 8, 12, 16, and 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 2, 4, 8, 12, 16, and 24	Participants answered the question: "How much pain have you had when walking on a flat surface?" Participants responded by using an 11-point scale where 0 = no pain and 10 = extreme pain. Where 0 is the best response and negative change indicated an improvement.	Baseline, Week 2, 4, 8, 12, 16, 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Downstairs at Weeks 2, 4, 8, 12, 16, and 24	Participants answered the question: "How much pain have you had when going up or down the stairs?" Participants responded by using an 11-point scale, where 0 = no pain and 10 = extreme pain. Where 0 is the best response and negative change indicated an improvement.	Baseline, Weeks 2, 4, 8, 12, 16, and 24
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 12 and 24	SF-36v2 was a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and role limitations due to emotional problems, bodily pain, general health, vitality, and mental health. The total score and the score for a section was an average of the individual question scores, which were scaled 0-100. Higher scores reflected better participant status and positive change indicated an improvement.	Baseline, Week 12, and 24
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 12 and 24	SF-36v2: standardized survey evaluating 8 aspects of functional health and wellbeing (physical and social functioning, role limitations due to physical and emotional problems, bodily pain, general health, vitality, mental health). Total score for each aspect were scaled 0-100. Higher scores reflect better participant status and positive change indicated an improvement. 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 and 24
Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Index Score at Week 24	EQ-5D was a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme dysfunction) and a single index value characterizing current health status using a visual analog scale with score ranging from 0 (worst) to 100 (best). EQ-5D summary index was obtained with a formula that weights each level of the dimensions. The index-based score was interpreted along a continuum of 0 (death) to 1 (perfect health). Negative change from baseline represented worsening.	Baseline, Week 24
Number of Participants With Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Individual Health State Profile at Week 24	EQ-5D was a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme dysfunction) and a single index value characterizing current health status using a visual analog scale with score ranging from 0 (worst) to 100 (best). Baseline EQ-5D individual health state profile was determined as number of participants "no dysfunction, moderate or some dysfunction and extreme dysfunction" and change from baseline in EQ-5D individual health state profile was determined as number of participants "improved, no change or worsened".	Baseline, Week 24
Number of Participants Who Discontinued Due to Lack of Efficacy	Number of participants who discontinued due to lack of efficacy were reported.	Baseline up to end of study (Week 32)
Time to Discontinuation (TTD) 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 and 24
Number of Participants With 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 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs as well as non-serious AEs which occurred during the trial.	Baseline up to 112 days after last intravenous dose (up to Week 32)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Intravenous Doses of Study Medication	Number of participants were reported based on the maximum number of intravenous (IV) doses of either tanezumab or placebo received.	Day 1 up to Week 16

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.
• Balanescu AR, Feist E, Wolfram G, Davignon I, Smith MD, Brown MT, West CR. Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial. Ann Rheum Dis. 2014 Sep;73(9):1665-72. doi: 10.1136/annrheumdis-2012-203164. Epub 2013 Jul 12.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2009
• Primary Completion (Actual): November 16, 2010
• Study Completion (Actual): November 24, 2010

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Arthritis monoclonal antibody nerve growth factor (NGF) anti-NGF tanezumab PF-04383119 RN-624 OA
• 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; Diclofenac; Tanezumab
• Other Study ID Numbers: A4091017; 2009-009318-41 (EudraCT Number); P3 6 MO OA HIP/KNEE DICLOFENAC (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.