Tanezumab and Nerve Function In Arthritis Patients

A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TANEZUMAB ON PERIPHERAL NERVE FUNCTION IN PATIENTS WITH OSTEOARTHRITIS.

Tanezumab reduces pain of osteoarthritis without affecting how nerve impulses are transmitted in sensory nerves.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: tanezumab; Biological: tanezumab; Other: 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): 220
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • Colorado
    • Aurora, Colorado, United States, 80014
      • JDP Medical Research, LLC
    • Centennial, Colorado, United States, 80112
      • Alpine Neurology
    • Centennial, Colorado, United States, 80112
      • Peak Anesthesia
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research, LLC
    • Atlantis, Florida, United States, 33462
      • Medical Specialists of the Palm Beaches
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center, Inc
    • Bradenton, Florida, United States, 34208
      • Manatee Internal Medicine
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Associates
    • Fort Myers, Florida, United States, 33919
      • Harris Bonnette, MD
    • Hollywood, Florida, United States, 33021
      • Sunrise Clinical Research, Inc.
    • Hollywood, Florida, United States, 33024
      • Sunrise Clinical Research, Inc
    • Miami, Florida, United States, 33183
      • International Research Associates, LLC
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic, Inc
    • Palm Harbor, Florida, United States, 34684
      • The Arthritis Center
    • Pembroke Pines, Florida, United States, 33028
      • Pembroke Clinical Trials
    • Pembroke Pines, Florida, United States, 33026
      • Pines Neurological Associates
    • Pembroke Pines, Florida, United States, 33028
      • Pines Neurological Associates
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Centers, Inc
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Center
    • Plantation, Florida, United States, 33317
      • Berma Research Group
    • Saint Petersburg, Florida, United States, 33713
      • Dale G. Bramlet, MD, P.L.
    • Saint Petersburg, Florida, United States, 33713
      • Carol L. Pappas MD, PhD
    • Saint Petersburg, Florida, United States, 33713
      • Carol L. Pappas, M.D. PhD
    • Sarasota, Florida, United States, 34232
      • Kennedy-White Orthopaedic Center
    • Sarasota, Florida, United States, 34232
      • Sarasota Center for Clinical Research
    • Sarasota, Florida, United States, 34232
      • Ronal Aung-Din, MD
    • Sarasota, Florida, United States, 34232
      • Ronald Aung-Din, MD
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • Arthritis & Rheumatic Care Center
    • South Miami, Florida, United States, 33143
      • Neuroscience Consultants, LLC
    • Tampa, Florida, United States, 33609
      • Tampa Neurology Associates
    • Tampa, Florida, United States, 33614
      • Tampa Medical Group, P.A.
    • Venice, Florida, United States, 34292
      • Venice Arthritis Center
    • Venice, Florida, United States, 34285
      • Radiology Associates of Venice & Englewood
    • Venice, Florida, United States, 34292
      • Lovelace Scientific Resources, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Incorporated
    • Atlanta, Georgia, United States, 30342
      • Atlanta Neurology
    • Atlanta, Georgia, United States, 30342
      • Diagnostic Imaging of Atlanta
    • Austell, Georgia, United States, 30106
      • Northwest Neurology, P.C.
    • Decatur, Georgia, United States, 30033
      • Neurology Specialists of Decatur
    • Decatur, Georgia, United States, 30033
      • Atlanta Knee And Sports Medicine
    • Decatur, Georgia, United States, 30033
      • Southeastern Center for Clinical Trials
    • Decatur, Georgia, United States, 30033
      • Joseph D. Weissman, MD
    • Decatur, Georgia, United States, 30333
      • Jefrey D. Lieberman, MD
  • Illinois
    • Bannockburn, Illinois, United States, 60015
      • Northwestern Lake Forest Hospital Diagnostic Imaging Centers
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology, Ltd.
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Elkhart Clinic, LLC
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46202
      • University Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • G. Timothy Kelly, MD
    • Las Vegas, Nevada, United States, 89146
      • Clinical Neurology Specialists
  • New York
    • Lake Success, New York, United States, 11042
      • Neurological Associates of Long Island, P.C.
    • Roslyn, New York, United States, 11576
      • Andrew J. Porges, M.D. PC
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Imaging
    • Asheville, North Carolina, United States, 28801
      • Biltmore Medical Associates
    • Asheville, North Carolina, United States, 28803
      • Clinical Study Center of Asheville, LLC
    • Asheville, North Carolina, United States, 28806-2287
      • Asheville Neurology
    • Hickory, North Carolina, United States, 28601
      • Unifour Medical Research Associates, LLC
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates, PA
    • Hickory, North Carolina, United States, 28602
      • Unifour Medical Research Associates, LLC
    • Lenoir, North Carolina, United States, 28645
      • Caldwell Memorial Hospital
    • Lenoir, North Carolina, United States, 28645
      • Northstate Clinical Research
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Ohio Research Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
    • Bend, Oregon, United States, 97701
      • North Star Neurology
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • Blair Neurologic Associates
    • Altoona, Pennsylvania, United States, 16602
      • Blair Orthopedic Associates, Inc.
    • Altoona, Pennsylvania, United States, 16602
      • Blair Medical Associates
    • Altoona, Pennsylvania, United States, 16601
      • Altoona Hospital Campus
    • Altoona, Pennsylvania, United States, 16602
      • Bon Secour Campus
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • Goose Creek, South Carolina, United States, 29445
      • Coastal Carolina Research Center in Goose Creek
    • Goose Creek, South Carolina, United States, 29445
      • Tidewater Neurology
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Diagnostic Clinic
    • Amarillo, Texas, United States, 79106
      • AAMR Research Clinic, PA
    • Dallas, Texas, United States, 75231
      • Radiant Research, Inc.
    • Dallas, Texas, United States, 75243
      • Dr. Michael Vengrow
    • Houston, Texas, United States, 77030
      • Foundation for Southwest Orthopedic Research
    • Houston, Texas, United States, 77030
      • The Neurology Center
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78229
      • Neurodiagnostic Laboratories of San Antonio, Inc
    • San Antonio, Texas, United States, 78205
      • Paragon Research Center, LLC
    • San Antonio, Texas, United States, 78229
      • Radiant Research Inc.
    • San Antonio, Texas, United States, 78215
      • Baptist M&S Imaging
    • San Antonio, Texas, United States, 78229
      • Christine L. Truitt, MD
    • San Antonio, Texas, United States, 78229
      • Neurodiagnostic Laboratories of San Antonio, Inc.
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Virginia Hospital Center
    • Arlington, Virginia, United States, 22205
      • IntegraTrials, L.L.C
    • Arlington, Virginia, United States, 22205
      • TLC Neurology, P.L.L.C
    • Roanoke, Virginia, United States, 24014
      • Hypothe Test, LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Everett, Washington, United States, 98201
      • Evergreen Neurology and Neurodiagnostics, PLLC

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:

• BMI less or equal to 39 kg/m2
• Osteoarthritis (arthritis) of the knee or hip with pain score that qualifies
• Willing to comply with study visit schedule and study requirements, including, for women of child-bearing potential or male patients with female partners of child-bearing potential, the use of 2 forms of birth control, one of which is a barrier method.
• Patients must consent in writing to participate in the study.

Exclusion Criteria:

• Untreated, uncontrolled diseases,
• Unwilling or unable to discontinue the use of prohibited medications, including other pain medications, during the screening period and during the study,
• Significant cardiac disease within the past 6 months
• Significant neurological disease (e.g. peripheral neuropathy, multiple sclerosis, stroke) or signs of neuropathy at screening
• Known bleeding disorder or anticoagulation therapy
• Planned surgery during the study period
• History of alcoholism or drug abuse in the past 2 years
• Unable to use acetaminophen
• Use of a biologic (including live vaccines, with the exception of Flumist) within the past 3 months
• Allergic reaction to a biologic or an antibody in the past
• Disqualifying laboratory values, including Hepatitis B or C, HIV or drug test
• Cancer in the past 5 years. Basal cell or squamous cell carcinoma are okay.
• Medical condition that may interfere with study endpoints or safety of the subject as determined by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo, Intravenously, every 8 weeks for duration of study
Experimental: Tanezumab 5 mg	Biological: tanezumab; 5 mg dose Intravenously every 8 weeks for duration of study; Biological: tanezumab; 10 mg dose Intravenously every 8 weeks for duration of study
Experimental: Tanezumab 10 mg	Biological: tanezumab; 5 mg dose Intravenously every 8 weeks for duration of study; Biological: tanezumab; 10 mg dose Intravenously every 8 weeks for duration of study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Intent to Treat (ITT) Analysis Set	5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency [MNDL],peroneal nerve compound muscle action potential[CMAP],peroneal motor nerve conduction velocity[MNCV],tibial MNDL,sural sensory nerve action potential amplitude [SNAP])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score >0=worse response,less than(<)0=better response compared to normal matched population.Score change>0=worsening,<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Per Protocol Analysis Set (PPAS)	5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency [MNDL],peroneal nerve compound muscle action potential[CMAP],peroneal motor nerve conduction velocity[MNCV],tibial MNDL,sural sensory nerve action potential amplitude [SNAP])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score >0=worse response,less than(<)0=better response compared to normal matched population.Score change>0=worsening,<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Neuropathy Impairment Score - Lower Limbs [NIS (LL)] at Week 24	NIS-LL: assess muscle weakness, reflexes, sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. NIS-LL score: sum of scores of NIS items 17-24, 28-29 and 34-37. Total possible NIS-LL score range 0-88, high score = more impairment.	Baseline, Week 24
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24	NIS: 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness are 24 items and scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes and sensation are 13 items and scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0 to 244, higher score = greater impairment.	Baseline, Week 24
Change From Baseline in Neuropathy Symptoms and Change (NSC) Score at Week 24	NSC score is the number of the 38 symptom questions where the participants indicated experiencing the symptom to any severity. Total score range: 0 to 38 where higher score indicated more symptoms. A change from Baseline > 0 indicated some symptoms of peripheral neuropathy.	Baseline, Week 24
Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: ITT Analysis Set	Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score <0 indicated worse response and >0 indicated better response than the normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the two NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: PPAS	Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score <0 indicated worse response and >0 indicated better response than the normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: ITT Analysis Set	Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score <0 indicated worse response and >0 indicated better response than the normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: PPAS	Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score <0 indicated worse response and >0 indicated better response than the normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set	Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score >0 indicated worse response and <0 indicated better response as compared to normal matched population. Score change >0 indicated worsening and <0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS	Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score >0 indicated worse response and <0 indicated better response as compared to normal matched population. Score change >0 indicated worsening and <0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set	Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score >0 indicated worse response and <0 indicated better response as compared to normal matched population. Score change >0 indicated worsening and <0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS	Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score >0 indicated worse response and <0 indicated better response as compared to normal matched population. Score change >0 indicated worsening and <0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: ITT Analysis Set	Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. A score <0 indicated worse response and >0 indicated better response than the normal matched population. A change <0 indicated worsening and >0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: PPAS	Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. A score <0 indicated worse response and >0 indicated better response than the normal matched population. A change <0 indicated worsening and >0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: ITT Analysis Set	HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score <0 indicated worse response and >0 indicated better response as compared to normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: PPAS	HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score <0 indicated worse response and >0 indicated better response as compared to normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in 5 Nerve Conduction Test - Normal Deviate [5NC (nd)] at Week 24: ITT Analysis Set	5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Total score calculated as sum of each NCS attribute. Total score >0 indicated worse and <0 indicated better response as compared to normal matched population. Total score change >0 indicated worsening and <0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in 5 Nerve Conduction Test - Normal Deviate (5NC [nd]) at Week 24: PPAS	5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Total score calculated as sum of each NCS attribute. Total score >0 indicated worse and <0 indicated better response as compared to normal matched population. Total score change >0 indicated worsening and <0 indicated improvement as compared to baseline.2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.	Baseline, Week 24
Change From Baseline in Protein Gene Product (PGP) 9.5-Positive Intraepidermal Epidermal Nerve Fiber (IENF) Density at Week 24	IENF density was quantified in 3 millimeter (mm) immunostained (PGP 9.5-immunohistochemical staining) skin punch biopsies taken from the distal end of the leg, 10 centimeter (cm) above the lateral malleolus, within the territory of the sural nerve, containing epidermis and superficial dermis to evaluate amount of small diameter nerve fibers. Skin biopsies were taken from normal appearing skin and skin having local scar, signs of trauma, ulceration, or active dermatologic process were avoided.	Baseline, Week 24
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 8, 16, and 24	WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.	Baseline, Weeks 8, 16, and 24
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 8, 16, and 24	WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function.	Baseline, Weeks 8, 16, and 24
Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 8, 16, and 24	Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition using a 5-point 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 severe condition.	Baseline, Weeks 8, 16, and 24
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response	OMERACT-OARSI response: >=50 percent (%) improvement from baseline and absolute change from baseline of >=2 units 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 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).	Weeks 8, 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	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint ( knee or hip) in the past 48 hours. It is calculated as the mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.	Weeks 8, 16, and 24
Percentage of Participants With Improvement of At Least 2 Points From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis	Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition using a 5-point 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 severe condition.	Weeks 8, 16, and 24
Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 are reported.	Week 16
Change From Baseline in Average Pain Score in the Index Knee/Hip Joint at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24	Participants assessed daily average index joint pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 8, 16, and 24	The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10, with higher scores indicating more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicate more stiffness. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip).	Baseline, Weeks 8, 16, and 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 8, 16, and 24	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 or hip. 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. Change from baseline <0 indicates an improvement.	Baseline, Weeks 8, 16, and 24
Change From Baseline in WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 8, 16, and 24	Participants answered: "How much pain have you had when walking on a flat surface?". Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain. Change from baseline <0 indicated an improvement.	Baseline, Weeks 8, 16, and 24
Change From Baseline in WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 8, 16, and 24	Participants answered: How much pain have you had when going up or down stairs?. Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain. Change from baseline <0 indicates an improvement.	Baseline, Weeks 8, 16, and 24
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 24	SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning). Change from baseline >0 indicates an improvement.	Baseline, Week 24
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 24	SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. Total score for each aspect were scaled 0-100(100=highest level of functioning). 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. Change from baseline >0 indicates an improvement.	Baseline, Week 24
Number of Participants With Rescue Medication Usage	In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.	Week 8, 16, 24
Number of Days With Rescue Medication Usage	In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Result reported is number of days of rescue medication use in each week, and ranges from 0 to 7.	Weeks 8, 16, and 24
Amount of Rescue Medication Used	In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Results reported is total dose of acetaminophen (in mg) for each week.	Weeks 8, 16, and 24
Number of Participants With Anti-Drug Antibody (ADA)	Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semiquantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point.	pre-dose on Day 1 (Baseline), Week 8, 16, 24, 32
Plasma Trough Concentration of Tanezumab	Plasma trough concentration of tanezumab was measured using a validated, sensitive and specific enzyme-linked immunosorbent assay (ELISA).	pre-dose on Day 1 (Baseline), Weeks 8, 16, 24, and 32
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. 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. AEs included both serious AEs and non-serious AEs.	Baseline through 112 days after last Intravenous dose of Investigational product to last participant treated with study medication on study (up to Week 32 after last IV dose of investigational product to last participant treated)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Intravenous Doses of Study Medication	Number of participants are reported based on the maximum number of intravenous (IV) doses of either tanezumab or placebo received.	Day 1 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.
• Brown MT, Herrmann DN, Goldstein M, Burr AM, Smith MD, West CR, Verburg KM, Dyck PJ. Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment. J Neurol Sci. 2014 Oct 15;345(1-2):139-47. doi: 10.1016/j.jns.2014.07.028. Epub 2014 Jul 18.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2009
• Primary Completion (Actual): November 16, 2010
• Study Completion (Actual): November 16, 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 4, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tanezumab
• Other Study ID Numbers: A4091026; NERVE SAFETY STUDY (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.