A Study of Tanezumab in Adults With Chronic Low Back Pain

A RANDOMIZED, DOUBLE-BLIND, MULTI-DOSE, ACTIVE- AND PLACEBO-CONTROLLED, MULTI-CENTER, PARALLEL GROUP STUDY OF THE ANALGESIC EFFECTS OF TANEZUMAB IN ADULT PATIENTS WITH CHRONIC LOW BACK PAIN

The purpose of this study is to evaluate the efficacy and safety of multiple doses of tanezumab administered every 8 weeks in treating chronic low back pain. Tanezumab is a monoclonal antibody directed against human nerve growth factor.

Study Overview

• Status: Completed
• Conditions: Low Back Pain
• Intervention / Treatment: Biological: Tanezumab 20 mg IV; Drug: Placebo for naproxen; Biological: Tanezumab 10 mg IV; Biological: Tanezumab 5 mg IV; Biological: Placebo for tanezumab; Drug: Naproxen

• Study Type: Interventional
• Enrollment (Actual): 1359
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group LLC
    • Anniston, Alabama, United States, 36201
      • Pinnacle Research Group, LLC
    • Birmingham, Alabama, United States, 35211
      • Simon Williamson Clinic, PC
    • Hueytown, Alabama, United States, 35023
      • Simon-Williamson Clinic, PC
    • Huntsville, Alabama, United States, 35801
      • Saadat Ansari, MD Office
    • Mobile, Alabama, United States, 36608
      • Horizon Research Group
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Radiant Research - Phoenix Southeast
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Centers
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research, Inc.: Scottsdale, AZ
    • Tempe, Arizona, United States, 85282
      • Premiere Phamaceutical Research, LLC
    • Tempe, Arizona, United States, 85283
      • Clinical Research Advantage, Inc./Fiel Family and Sports Medicine, PC
    • Tucson, Arizona, United States, 85745
      • Alta Clinical Research, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Family Practice Clinic
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Fresno, California, United States, 93720
      • Valley Research
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc
    • La Jolla, California, United States, 92121
      • University of California San Diego
    • Los Gatos, California, United States, 95032
      • Samaritan Center for Medical Research Medical Group
    • Oceanside, California, United States, 92056
      • North County Clinical Research (NCCR)
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
    • Roseville, California, United States, 95661
      • Quality Control Research, Inc
    • Sacramento, California, United States, 95823
      • Center for Clinical Trials of Sacramento, Inc.
    • San Diego, California, United States, 92120
      • Wetlin Research Associates, Inc
    • Upland, California, United States, 91786
      • Inland Rheumatology & Osteoporosis Medical Group, Inc.
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
    • Colorado Springs, Colorado, United States, 80904
      • Clinicos, LLC
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Florida
    • Chiefland, Florida, United States, 32626
      • Southeast Clinical Research
    • Chiefland, Florida, United States, 32626
      • Southeast Clinical Research, LLC
    • DeFuniak Springs, Florida, United States, 32435
      • Doctors Medical center of Walton County
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Destin, Florida, United States, 32541
      • SJS Clinical Research, Inc.
    • Fort Lauderdale, Florida, United States, 33334
      • CRIA Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Southeast Clinical Research, LLC
    • Naples, Florida, United States, 34102
      • Collier Neurologic Specialists
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research Incorporated
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Center
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Saint Petersburg, Florida, United States, 33713
      • Dale G. Bramlet, MD
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • Arthntis & Rheumatic Care Center
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Center for Prospective Outcome Studies
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance, Llc
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Idaho
    • Boise, Idaho, United States, 83704
      • Selah Medical Center, PA
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Kansas
    • Overiand Park, Kansas, United States, 66211
      • Vince and Associates Clinical Research
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc.
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Association, Inc.
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Arthritis and Diabetes Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • Peter A. Holt, MD
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Lansing, Michigan, United States, 48917
      • PCM Medical Services
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • The Center for Clinical Trials
    • Jackson, Mississippi, United States, 39202
      • Physician's Surgery Center
    • Jackson, Mississippi, United States, 39202
      • Clinical Research Center of Jackson
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
    • Saint Louis, Missouri, United States, 63117
      • Medex Healthcare Research, Inc.
    • Springfield, Missouri, United States, 65807
      • Clinvest/ A Division Of Banyan Group, Inc.
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium
    • Las Vegas, Nevada, United States, 89119
      • Mirkil Medical
    • Las Vegas, Nevada, United States, 89123
      • Advanced Biomedical Research of America
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
    • New York, New York, United States, 10128
      • The Medical Research Network, LLC
    • New York, New York, United States, 10004
      • Medex Healthcare Research, Inc.
    • New York, New York, United States, 10004
      • Medex Healthcare Research
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Lenoir, North Carolina, United States, 28645
      • Northstate Clinical Research, PLLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Community Research
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • McBride Clinic
    • Oklahoma City, Oklahoma, United States, 73103
      • Christine Codding, MD
  • Oregon
    • Medford, Oregon, United States, 97504
      • Sunstone Medical Research, LLC
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon), Inc.
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Allegheny Pain Management
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, Pc
    • Bridgeville, Pennsylvania, United States, 15017
      • Paramount Clinical Research
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide LLC
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • New England Center for Clinical Research
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Southern Orthopaedic Sports Medicine
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center, P.A.
    • Greer, South Carolina, United States, 29651
      • Radiant Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • SCRI Research Center
    • Germantown, Tennessee, United States, 38138
      • Wolf River Medical Group, LLC
    • Johnson City, Tennessee, United States, 37601
      • Advanced Therapeutics, Inc.
    • Johnson City, Tennessee, United States, 37601
      • Johnson City Internal Medicine
  • Texas
    • Austin, Texas, United States, 78756
      • FutureSearch Trials
    • Austin, Texas, United States, 78705
      • Capitol Medical Clinic
    • Austin, Texas, United States, 78705
      • Walter F. Chase, MD, PA
    • Austin, Texas, United States, 78756
      • FutureSearch Trials of Neurology
    • Beaumont, Texas, United States, 77701
      • DiscoveResearch, Inc.
    • Bryan, Texas, United States, 77802
      • DiscoveResearch, Incorporated
    • Carrollton, Texas, United States, 75006
      • Trinity Hypertension & Metabolic Research Institute Punzi Medical Center
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Houston, Texas, United States, 77030
      • Advances in Health, Inc.
    • Houston, Texas, United States, 77062
      • Centex Research, Inc.
    • Houston, Texas, United States, 77065
      • Centex Research
    • Nassau Bay, Texas, United States, 77058
      • Centex Research
    • San Antonio, Texas, United States, 78229
      • Paragon Research Center
    • San Antonio, Texas, United States, 78229
      • Progressive Clinical Research, PA
    • San Antonio, Texas, United States, 78229
      • Office of Theresia Lee, MD
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121-6924
      • Foothill Family Clinic
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Incorporated
    • Virginia Beach, Virginia, United States, 23454
      • Advanced Pain Management
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Present with duration of low back pain of ≥3 months requiring regular use of analgesic medication (>4 days per week for the past month). Analgesic medication may consist of NSAIDs, selective COX-2 inhibitors, immediate release opioids, or combinations, with certain protocol-defined limitations.
• Primary location of low back pain must be between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation into the posterior thigh
• Must meet criteria for pain severity and global assessment of low back pain at Screening and Baseline visits
• Female patients of child-bearing potential (and male patients with female partners who are of child-bearing potential) must use 2 methods of contraception throughout the study
• Patients must be willing to discontinue all pain medications for chronic low back pain except rescue medication and not use prohibited pain medications throughout the duration of the study

Exclusion Criteria:

• History of lumbosacral radiculopathy within the past 2 years.
• Back pain due to visceral disorder (eg, endometriosis).
• Back pain due to major trauma or osteoporotic compression fracture in the past 6 months.
• History of rheumatoid arthritis, seronegative spondyloarthropathy, Paget's disease of spine, pelvis or femur; fibromyalgia; tumors or infections of the spinal cord.
• Surgical intervention during the past 6 months for the treatment of low back pain or plans for surgical intervention during the course of the study.
• Current or pending worker's compensation, litigation, disability, or any other monetary settlement regarding his/her CLBP or any other pain condition, or any closed claim within the past 5 years.
• Use of any analgesic or muscle relaxant within 48 hours prior to the five days before Baseline
• Patients receiving only acetaminophen, gabapentin or pregabalin to manage their chronic low back pain.
• Patients taking >325 mg/day of aspirin.
• Use of any antidepressants with the exception of stable treatment with selective serotonin reuptake inhibitors (SSRIs).
• Use of any sedatives/hypnotics, anxiolytics, tranquilizers, or benzodiazepines unless daily dose has been stable and will remain unchanged throughout the study period.
• Systemic corticosteroid therapy within 30 days (inhaled and topical corticosteroids are permitted).
• Local or epidural injection of corticosteroids, as well as injections of corticosteroids in the back within 3 months.
• Botulinum toxin (Botox®) injection for chronic low back pain within 4 months.
• Requirement for new, concomitant physiotherapy including, but not limited to, transdermal electroneural stimulation (TENS), massage or spinal manipulation for the duration of the study period.
• Active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration within 3 months, or any history of gastrointestinal bleeding.
• Current use of lithium or anticoagulant agents.
• Known hypersensitivity or intolerance to NSAIDs; history of asthma, urticaria, or allergic type reactions after taking aspirin or NSAIDs.
• Inflammatory bowel disease, a chronic or acute renal or hepatic disorder, a significant coagulation defect, or other condition that might preclude the use of an NSAID.
• History of intolerance to acetaminophen or paracetamol or any of its excipients.
• History of known alcohol, analgesic or narcotic abuse within 2 years.
• Presence of drugs of abuse (including prescription medications without a valid prescription), other illegal drugs or marijuana in the urine toxicology screen obtained at Screening.
• History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein.
• Use of biologics other than study medication, including any live vaccines, within 3 months, or use during the study (intranasal Flumist® vaccine is an exception).
• Signs and symptoms of clinically significant cardiac disease.
• Diagnosis of a transient ischemic attack within the 6 months, or residual deficits from stroke that would preclude completion of required study activities.
• History of cancer within 5 years.
• Use of any investigational medication within 30 days (3 months for investigational biologics).
• Expected to undergo a therapeutic procedure or to use any analgesic other than those specified in the protocol throughout the study period.
• Previous exposure to exogenous NGF or to an anti NGF antibody.
• Screening laboratory results and blood pressure within specified limits.
• Positive Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) tests at screening.
• History, diagnosis, or signs and symptoms of clinically significant neurological disease.
• History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder.
• Hospital admission for depression or suicide attempt within 5 years or active, severe major depression at Screening.
• Likelihood of being non compliant with study procedures.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo for naproxen; Oral placebo for naproxen twice a day for 16 weeks; Biological: Placebo for tanezumab; 2 IV administrations of placebo for tanezumab at an 8 week interval
Active Comparator: Naproxen	Biological: Placebo for tanezumab; 2 IV administrations of placebo for tanezumab at an 8 week interval; Drug: Naproxen; Oral naproxen 500 mg twice a day for 16 weeks
Experimental: Tanezumab 20 mg IV	Biological: Tanezumab 20 mg IV; 2 IV administrations of tanezumab 20 mg at an 8 week interval; Drug: Placebo for naproxen; Oral placebo for naproxen twice a day for 16 weeks
Experimental: Tanezumab 10 mg IV	Drug: Placebo for naproxen; Oral placebo for naproxen twice a day for 16 weeks; Biological: Tanezumab 10 mg IV; 2 IV administrations of tanezumab 10 mg at an 8 week interval
Experimental: Tanezumab 5 mg IV	Drug: Placebo for naproxen; Oral placebo for naproxen twice a day for 16 weeks; Biological: Tanezumab 5 mg IV; 2 IV administrations of tanezumab 5 mg at an 8 week interval

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 16: Baseline Observation Carried Forward (BOCF)	Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit. Overall possible score range for daily average LBPI at specified visit was 0= no pain to 10= worst possible pain, where higher scores indicated higher pain intensity.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Discontinuation Due to Lack of Efficacy	Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method.	Baseline up to Week 16
Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	RMDQ: back-specific, participant administered questionnaire that assesses how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement if it describes his/her functional ability on the day of assessment. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements marked. Total possible RMDQ score: 0 (best functioning) to 24 (worst functioning), with higher scores indicated greater disability.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	Participants answered: "Considering all ways your low back pain affects you, how are you doing today?" Participants rated their condition using scale assessing symptoms and limitations to carry out normal daily activities. Score range:1 to 5. 1: Very Good (No symptoms and limitations); 2: Good (Mild symptoms and no limitations); 3: Fair (Moderate symptoms and some limitations); 4: Poor (Severe symptoms and inability to carry out most activities); 5: Very Poor (Very severe, intolerable symptoms and inability to carry all activities).	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)	Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit.	Baseline, Week 2, 4, 8, 12
Number of Participants With Cumulative Reduction From Baseline at Week 16 in Daily Average Low Back Pain Intensity (LBPI) Score : Baseline Observation Carried Forward (BOCF)	Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit. Participants with specified reduction (as percent) from baseline at Week 16 are reported.	Baseline, Week 16
Percentage of Participants With at Least 30 Percent (%) and 50% Reduction From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)	Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score for Worst and Average Pain at Week 2, 4, 8, 12, 16: Baseline Observation Carried Forward (BOCF)	BPI-sf: self-report questionnaire rated on an 11-point scale, consists of 5 questions to assess severity and impact of pain on daily functions. Question 1-4 (Q1-Q4) measure severity of pain (worst, least, average, right now), each question ranging between 0 (no pain) to 10 (pain as bad as you can imagine). Question 5 (Q5) consists of 7 items which measure level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), each item ranging from 0 (does not interfere) to 10 (completely interferes). Results are reported for worst and average pain, each with a score range: 0 (no pain) and 10 (pain as bad as you can imagine), higher scores indicated worse pain.	Baseline, Week 2, 4, 8, 12, 16
Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score for Pain Interference Index, Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 2, 4, 8, 12 and 16: BOCF	BPI-sf: self-report questionnaire rated on an 11-point scale, consists of 5 questions to assess severity and impact of pain on daily functions. Question 1-4 (Q1-Q4) measure severity of pain (worst, least, average, right now), each question ranging between 0 (no pain) to 10 (pain as bad as you can imagine). Question 5 (Q5) consists of 7 items which measure pain interference (PI) on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), each item ranging from 0 (does not interfere) to 10 (completely interferes); higher score = greater impairment. The 7 items in Q5 averaged to obtain pain interference index (function composite score), range: 0 (no interference) to 10 (complete interference); higher score = greater impairment.	Baseline, Week 2, 4, 8, 12, 16
Number of Participants With Chronic Low Back Pain (CLBP) Responder Index: Baseline Observation Carried Forward (BOCF)	Chronic Low Back Pain (CLBP) Responder Index: A response was defined as reduction of at least 30% in mean daily average LBPI from baseline to a specified week, decrease of at least 30% in PGA of low back pain from baseline to the specified week and no worsening (increase) in RMDQ total score from baseline to the specified week. Participants who were responders were reported.	Week 2, 4, 8, 12, 16
Change From Baseline in Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) at Week 8 and 16	WPAI:SHP is a self-administered questionnaire that measures the effect of general health and symptom severity on work productivity and regular activities. Four scores are derived as percent: activity impairment (AI), impairment while working (IW), overall work impairment (OWI), work time missed (WTM). Each of 4 scores expressed as impairment percentages with a total possible score range of 0 to 100, high percentage= more impairment, less productivity.	Baseline, Week 8, 16
Percentage of Participants Who Used Rescue Medications	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.	Week 2, 4, 8, 12, 16
Duration of Rescue Medication Use	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.	Week 2, 4, 8, 12, 16
Amount of Rescue Medication Taken	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.	Week 2, 4, 8, 12, 16
Change From Baseline Neuropathy Impairment Score (NIS) at Week 8, 16 and 24	NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.	Baseline, Week 8, 16, 24
Number of Participants Who Developed Anti-Tanezumab Antibodies	Human serum anti-drug antibody (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 (Day 1), Week 8, 16, 24
Plasma Concentration of Tanezumab	Analysis was done by setting concentration values below the lower limit of quantification (LLOQ) to zero.	Baseline (pre-dose and 1 hour [hr] post-dose); Any time point at Week 4 Visit; Week 8 (pre-dose and 1 hr post-dose); Any time point at Week 16 Visit, at Week 24 Visit
Total Nerve Growth Factor (NGF) Concentration		Baseline (pre-dose and 1 hour [hr] post-dose); Any time point at Week 4 Visit; Week 8 (pre-dose and 1 hr post-dose); Any time point at Week 16 Visit, at Week 24 Visit
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 Week 24 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 Week 24

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.
• Kivitz AJ, Gimbel JS, Bramson C, Nemeth MA, Keller DS, Brown MT, West CR, Verburg KM. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain. Pain. 2013 Jul;154(7):1009-21. doi: 10.1016/j.pain.2013.03.006. Epub 2013 Mar 14.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2009
• Primary Completion (Actual): June 16, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: April 3, 2009
• First Submitted That Met QC Criteria: April 3, 2009
• First Posted (Estimate): April 6, 2009

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: randomized controlled trial; monoclonal antibody; naproxen; nerve growth factor
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Tanezumab; Naproxen
• Other Study ID Numbers: A4091012; CLBP-IV PH2B (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.