Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging Study

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

This is an efficacy and safety study of 3 doses (2.5 mg, 5 mg and 10mg) of tanezumab administered subcutaneously versus placebo. This study will also compare a subcutaneous (SC) administration of 10 mg of tanezumab) with an intravenous (IV) administration of 10 mg of tanezumab. Each person will receive an IV infusion and a SC infusion. The study will last 16 weeks for those who wish to enter a 64-week extension study or 24 weeks for those who do not.

Study Overview

• Status: Terminated
• Conditions: Pain; Arthritis; Osteoarthritis
• Intervention / Treatment: Biological: Placebo IV; Biological: Placebo SC; Biological: Placebo IV; Biological: Placebo IV; Biological: Placebo SC; Biological: Tanezumab SC; Biological: Tanezumab IV

Detailed Description

This study was terminated on 08 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): 385
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36117
      • Vaughn H. Mancha, Jr., MD, PC
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Novara Clinical Research
    • Phoenix, Arizona, United States, 85029
      • Redpoint Research
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Anaheim, California, United States, 92801
      • West Coast Radiology Center
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Fresno, California, United States, 93720
      • Valley Research
    • La Jolla, California, United States, 92037-1233
      • Allergy and Rheumatology Medical Clinic, Inc.
    • La Mesa, California, United States, 91942
      • Triwest Research Associates
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Sacramento, California, United States, 95816
      • Benchmark Research
    • Santa Ana, California, United States, 92701
      • Trinity Clinical Trials
    • Santa Ana, California, United States, 92701
      • Probe Clinical Research Corp.
    • Upland, California, United States, 91786
      • FMC Clinical Trials
  • Colorado
    • Englewood, Colorado, United States, 80110
      • Colorado Hematology
    • Englewood, Colorado, United States, 80110
      • Colorado Orthopedic Consultants, P.C.
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • District of Columbia
    • Washington, District of Columbia, United States, 20003
      • Office of Cynthia Morgan, MD
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Crystal River, Florida, United States, 34429
      • Nature Coast Clinical Research
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Largo, Florida, United States, 33777
      • BayCare Outpatient Imaging at Bardmoor
    • Opa-locka, Florida, United States, 33054
      • Sunshine Research Center
    • Pinellas Park, Florida, United States, 33782
      • DMI Research, Inc.
    • Saint Petersburg, Florida, United States, 33710
      • St. Petersburg Arthritis Center
  • Georgia
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Internal Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Boise, Idaho, United States, 83702
      • Sonora Clinical Research
    • Boise, Idaho, United States, 83702
      • Sonoma Clinical Research, LLC.
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Apex Medical Research, AMR, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas, LLC
    • Wichita, Kansas, United States, 67208
      • Wichita Clinic PA
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research, Inc.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis Treatment Center
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research, LLC
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Ann Arbor Clinical Reserch
    • Troy, Michigan, United States, 48098
      • Troy Internal Medicine, PC
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39402
      • Arthritis Associates, PLLC
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Research Center
    • Billings, Montana, United States, 59101
      • Billings Clinic Infusion Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
    • Omaha, Nebraska, United States, 68114
      • Midwest Minor Medical
    • Omaha, Nebraska, United States, 68127
      • Midwest Minor Medical
    • Omaha, Nebraska, United States, 68144
      • Midwest Minor Medical
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • G. Timothy Kelly, MD
  • New York
    • Roslyn, New York, United States, 11576
      • Andrew Porges, MD, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28209-3734
      • PMG Research of Charlotte
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Greensboro, North Carolina, United States, 27407
      • Greensboro Imaging
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Community Research
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Lion Research
    • Norman, Oklahoma, United States, 73072
      • McBride Clinic
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Lebanon, Pennsylvania, United States, 17042
      • Lebanon Internal Medicine Associates
    • Philadelphia, Pennsylvania, United States, 19152
      • Founders Research Corporation
    • Wyomissing, Pennsylvania, United States, 19610
      • 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
      • SoFHA Clinical Research
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc.
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77005
      • Westbury Medical Clinic
    • Houston, Texas, United States, 77074
      • Houston Institute For Clinical Research
    • Houston, Texas, United States, 77036
      • Pioneer Research Solutions, Inc
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research
    • Houston, Texas, United States, 77036
      • Mercury Clinical Research
    • Houston, Texas, United States, 77008
      • Asif Cochinwala, MD, P.A.
    • Houston, Texas, United States, 77093
      • Little York Medical Center
    • Kingwood, Texas, United States, 77339
      • Internist Associates of Texas
    • Nassau Bay, Texas, United States, 77058
      • Accurate Clinical Research Inc
    • Plano, Texas, United States, 75075
      • Clinical Investigations of Texas, LLC
    • San Angelo, Texas, United States, 76904
      • Benchmark Research
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions, Inc
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Roanoke, Virginia, United States, 24018
      • Hypothe Test, LLC
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research

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:

• Diagnosis of osteoarthritis (OA) of the knee according to American College of Rheumatology (ACR) criteria with a Kellgren- Lawrence score of greater than or equal to 2
• 18 years of age or greater
• Two methods of birth control one of which must be barrier if of childbearing potential
• Willing to discontinue pain medication except as permitted per protocol

Exclusion Criteria:

• Pregnancy or wishing to be pregnant during the course of the study, lactating women
• Body Mass Index (BMI) greater than 39
• Clinically significant cardiac, neurological, psychiatric conditions and other conditions that are excluded by the protocol.
• Previous exposure to a Nerve Growth Factor (NGF) antibody

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Biological: Placebo IV; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo SC; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo IV; 1 ml placebo administered IV every 8 weeks; Biological: Placebo IV; 1ml placebo administered IV every 8 weeks; Biological: Placebo SC; 1ml placebo administered SC every 8 weeks
EXPERIMENTAL: 2.5 mg tanezumab SC and placebo IV	Biological: Placebo IV; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo IV; 1 ml placebo administered IV every 8 weeks; Biological: Placebo IV; 1ml placebo administered IV every 8 weeks; Biological: Tanezumab SC; 1 ml tanezumab injection SC administered every 8 weeks
EXPERIMENTAL: 5 mg tanezumab SC and placebo IV	Biological: Placebo IV; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo IV; 1 ml placebo administered IV every 8 weeks; Biological: Placebo IV; 1ml placebo administered IV every 8 weeks; Biological: Tanezumab SC; 1 ml tanezumab injection SC administered every 8 weeks
EXPERIMENTAL: 10 mg tanezumab SC and placebo IV	Biological: Placebo IV; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo IV; 1 ml placebo administered IV every 8 weeks; Biological: Placebo IV; 1ml placebo administered IV every 8 weeks; Biological: Tanezumab SC; 1 ml tanezumab injection SC administered every 8 weeks
EXPERIMENTAL: 10 mg tanezumab IV	Biological: Placebo SC; 1 ml of placebo administered SC and IV once every 8 weeks.; Biological: Placebo SC; 1ml placebo administered SC every 8 weeks; Biological: Tanezumab IV; 1 ml tanezumab injection IV administered every 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee 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, Week 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16	The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint 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, Week 16
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis Score at Week 16	Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by 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, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 1, 2, 4, 8, and 12	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee 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 1, 2, 4, 8, and 12
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 1, 2, 4, 8, and 12	The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint 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 1, 2, 4, 8, and 12
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Weeks 1, 2, 4, 8, and 12	Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by 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 1, 2, 4, 8, and 12
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response	The OMERACT-OARSI responder index is based on 3 parameters. OMERACT-OARSI response: greater than or equal to (>=) 50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score range: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score range: 0-10, higher score=higher pain/difficulty).	Weeks 1, 2, 4, 8, 12, and 16
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 knee 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.	Weeks 1, 2, 4, 8, 12, and 16
Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score at Weeks 1, 2, 4, 8, 12, and 16	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a 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.	Weeks 1, 2, 4, 8, 12, 16
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis	Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by 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. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value.	Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline in Average Pain Score in the Index Knee at Weeks 1, 2, 4, 8, 12 and 16	Participants assessed average osteoarthritis pain in their knee in the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain. Baseline score was calculated as the mean of the scores over the 3 days in the initial pain assessment period and a weekly mean was calculated using the daily pain scores within each study week.	Baseline, Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 1, 2, 4, 8, 12, and 16	The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced in the index joint 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 is defined as a sensation of decreased ease in movement of the knee.	Baseline, Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 1, 2, 4, 8, 12, and 16	WOMAC: self-administered, disease-specific 24-item questionnaire, which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis of knee. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores. WOMAC pain, physical function and stiffness subscale and average score ranges from 0 to 10, where higher score indicates worse response.	Baseline, Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 1, 2, 4, 8, 12, and 16	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.	Baseline, Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 1, 2, 4, 8, 12, and 16	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.	Baseline, Weeks 1, 2, 4, 8, 12, and 16
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 16	SF-36v2 is a standardized self-administered survey evaluating 8 aspects/domains of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning).	Baseline, Week 16
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 16	SF-36v2: standardized self-administered survey evaluating 8 aspects of functional health and wellbeing (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each 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.	Baseline, Week 16
Time to Discontinuation Due to Lack of Efficacy	Median time to discontinuation due to lack of efficacy for participants who discontinued due to lack of efficacy was reported.	Baseline up to Week 24
Percentage of Participants Who Used Rescue Medication	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Incidence of rescue medication use is calculated as any use of rescue medication during the study week in question.	Weeks 1, 2, 4, 8, 12, and 16
Duration of Rescue Medication Use	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Duration of rescue medication use is calculated as the number of study days per week when any rescue medication was taken.	Weeks 1, 2, 4, 8, 12, and 16
Amount of Rescue Medication Taken	In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. The amount of rescue medication taken is the total dose (in mg) of acetaminophen rescue medication over the study week in question.	Weeks 1, 2, 4, 8, 12, and 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 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to 112 days after last dose of study treatment
Number of Participants With Abnormal Laboratory Findings	Laboratory examination included blood chemistry, hematology and urinalysis. Reported results include abnormal laboratory findings without regard to baseline abnormality.	Day 1 up to Week 24
Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate (HR). Number of participants with clinically significant abnormal ECG findings reported as adverse events were presented.	Baseline up to Week 24
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, and 24	The NIS constitutes the sum of 37 standard items of neuromuscular examination used to assess the muscle strength, reflexes and sensation. Each item is scored separately for left and right sides. Components of muscle weakness (24 items) are scored on a scale from 0 (normal) to 4 (paralysis), with higher score = more weakness; components of reflexes and sensation (13 items) scored on a scale with 0 = normal, 1 = decreased or 2 = absent. Total NIS score range 0-244 with higher score = more impairment.	Baseline, Weeks 2, 4, 8, 12, 16, and 24
Number of Participants With Anti-drug Antibodies (ADA)	Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point.	Baseline, Weeks 8, 16, 24 or Early Termination
Number of Participants With Abnormal Physical Examination Findings	Physical examination included examination of following sites in addition to general examination: abdomen, ears, extremities, eyes, head, heart, musculoskeletal, neck, nose, skin, throat, lungs and thyroid.	Baseline up to Week 24
Number of Participants With Clinically Significant Abnormality in Vital Signs	Following parameters were analyzed for examination of vital signs: body temperature, blood pressure, pulse rate and respiratory rate. Number of participants with clinically significant abnormality in vital signs reported as adverse events were presented.	Baseline to Week 24
Number of Participants With Injection and Infusion Site Reactions	The injection and infusion site reactions were assessed based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after administration of subcutaneous injection or intravenous infusion.	Baseline, Weeks 1, 2, 4, 8, 12, 16, and 24
Plasma Tanezumab Concentration		Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, 24 or End of treatment
Total and Free Nerve Growth Factor (NGF) Concentration	Serum samples were analyzed for determining total and free (unbound) NGF concentration. Total NGF was analyzed using a validated, sensitive and specific immunoaffinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method and free (unbound) NGF was analyzed using a validated, sensitive, and specific electrochemiluminescence (ECL) ligand binding assay.	Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, and 24 or End of treatment
Number of Participants With Intravenous or Subcutaneous Doses of Study Medication	Number of participants were reported based on the maximum number of intravenous or subcutaneous doses of either tanezumab or placebo received.	Baseline up to Week 8

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.
• Berenbaum F, Schnitzer T, Kivitz A, Viktrup L, Johnston E, Yang R, Whalen E, Tive L, Semel D. Gender, age, disease severity, body mass index and diabetes may not affect response to subcutaneous tanezumab in patients with osteoarthritis after 16 weeks of treatment. A subgroup analysis of placebo-controlled trials. Int J Clin Pract. 2021 Dec;75(12):e14975. doi: 10.1111/ijcp.14975. Epub 2021 Oct 21.
• Berenbaum F, Schnitzer TJ, Kivitz AJ, Viktrup L, Hickman A, Pixton G, Brown MT, Davignon I, West CR. General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2022 Jun;74(6):918-928. doi: 10.1002/acr.24637. Epub 2022 Mar 25.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 30, 2010
• Primary Completion (ACTUAL): November 8, 2010
• Study Completion (ACTUAL): February 18, 2011

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 17, 2010
• First Posted (ESTIMATE): March 18, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: osteoarthritis; safety; subcutaneous; efficacy; multicenter; infusion; double-blind; parallel group; intravenous; injection; tanezumab; bridging
• 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: A4091027; SC/IV OA STUDY (OTHER: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.