Clinical trial NCT00876187: A Study of Tanezumab in Adults With Chronic Low Back Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low Back Pain
Keywords: randomized controlled trial
monoclonal antibody
nerve growth factor
naproxen
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-04-06
Enrollment: 1359
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 16: Baseline Observation Carried Forward (BOCF)
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)
timeFrame: Baseline, Week 2, 4, 8, 12, 16
measure: 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)
timeFrame: Baseline, Week 2, 4, 8, 12, 16
measure: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)
timeFrame: Baseline, Week 2, 4, 8, 12
measure: 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)
timeFrame: Baseline, Week 16
measure: 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)
timeFrame: Baseline, Week 2, 4, 8, 12, 16
measure: 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)
timeFrame: Baseline, Week 2, 4, 8, 12, 16
measure: 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
timeFrame: Baseline, Week 2, 4, 8, 12, 16
measure: Time to Discontinuation Due to Lack of Efficacy
timeFrame: Baseline up to Week 16
measure: Number of Participants With Chronic Low Back Pain (CLBP) Responder Index: Baseline Observation Carried Forward (BOCF)
timeFrame: Week 2, 4, 8, 12, 16
measure: Change From Baseline in Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) at Week 8 and 16
timeFrame: Baseline, Week 8, 16
measure: Percentage of Participants Who Used Rescue Medications
timeFrame: Week 2, 4, 8, 12, 16
measure: Duration of Rescue Medication Use
timeFrame: Week 2, 4, 8, 12, 16
measure: Amount of Rescue Medication Taken
timeFrame: Week 2, 4, 8, 12, 16
measure: Change From Baseline Neuropathy Impairment Score (NIS) at Week 8, 16 and 24
timeFrame: Baseline, Week 8, 16, 24
measure: Number of Participants Who Developed Anti-Tanezumab Antibodies
timeFrame: Baseline (Day 1), Week 8, 16, 24
measure: Plasma Concentration of Tanezumab
timeFrame: 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
measure: Total Nerve Growth Factor (NGF) Concentration
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Birmingham
country: United States
facility: Simon Williamson Clinic, PC
state: Alabama
city: Hueytown
country: United States
facility: Simon-Williamson Clinic, PC
state: Alabama
city: Huntsville
country: United States
facility: Saadat Ansari, MD office
state: Alabama
city: Mobile
country: United States
facility: Horizon Research Group
state: Alabama
city: Chandler
country: United States
facility: Radiant Research - Phoenix Southeast
state: Arizona
city: Peoria
country: United States
facility: Pivotal Research Centers
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Scottsdale
country: United States
facility: Radiant Research, Inc.: Scottsdale, AZ
state: Arizona
city: Tempe
country: United States
facility: Premiere Phamaceutical Research, LLC
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc./Fiel Family and Sports Medicine, PC
state: Arizona
city: Tucson
country: United States
facility: Alta Clinical Research, LLC
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Family Practice Clinic
state: Arkansas
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Gatos
country: United States
facility: Samaritan Center for Medical Research Medical Group
state: California
city: Oceanside
country: United States
facility: North County Clinical Research (NCCR)
state: California
city: Rancho Mirage
country: United States
facility: Advances in Medicine
state: California
city: Roseville
country: United States
facility: Quality Control Research, Inc
state: California
city: Sacramento
country: United States
facility: Center for Clinical Trials of Sacramento, Inc.
state: California
city: San Diego
country: United States
facility: Wetlin Research Associates, Inc
state: California
city: Upland
country: United States
facility: Inland Rheumatology & Osteoporosis Medical Group, Inc.
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Colorado Springs
country: United States
facility: Clinicos, LLC
state: Colorado
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Trumbull
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Chiefland
country: United States
facility: Southeast Clinical Research, LLC
state: Florida
city: Chiefland
country: United States
facility: Southeast Clinical Research
state: Florida
city: DeFuniak Springs
country: United States
facility: Doctors Medical Center of Walton County
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Destin
country: United States
facility: SJS Clinical Research, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: CRIA Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Southeast Clinical Research, LLC
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Pembroke Pines
country: United States
facility: University Clinical Research Incorporated
state: Florida
city: Pinellas Park
country: United States
facility: Advent Clinical Research Center
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Saint Petersburg
country: United States
facility: Dale G. Bramlet, MD
state: Florida
city: South Miami
country: United States
facility: Arthntis & Rheumatic Care Center
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Center for Prospective Outcome Studies
state: Georgia
city: Blue Ridge
country: United States
facility: River Birch Research Alliance, LLC
state: Georgia
city: Marietta
country: United States
facility: Drug Studies America
state: Georgia
city: Boise
country: United States
facility: Selah Medical Center, PA
state: Idaho
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Overiand Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Prairie Village
country: United States
facility: Clinical Trials Technology, Inc.
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Association, Inc.
state: Kentucky
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research, LLC
state: Kentucky
city: Monroe
country: United States
facility: Arthritis and Diabetes Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Peter A. Holt, MD
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Lansing
country: United States
facility: PCM Medical Services
state: Michigan
city: Biloxi
country: United States
facility: The Center for Clinical Trials
state: Mississippi
city: Jackson
country: United States
facility: Clinical Research Center of Jackson
state: Mississippi
city: Jackson
country: United States
facility: Physician's Surgery Center
state: Mississippi
city: Saint Louis
country: United States
facility: Medex Healthcare Research, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Health Research
state: Missouri
city: Springfield
country: United States
facility: Clinvest/ A Division of Banyan Group, Inc.
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: Las Vegas
country: United States
facility: Mirkil Medical
state: Nevada
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Willingboro
country: United States
facility: CRI Worldwide
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Manlius
country: United States
facility: Central New York Clinical Research
state: New York
city: New York
country: United States
facility: Medex Healthcare Research, Inc.
state: New York
city: New York
country: United States
facility: Medex Healthcare Research
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Greensboro
country: United States
facility: Pharmquest
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research, PLLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Internal Medicine Consultants, Inc.
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center for Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Christine Codding, MD
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Oklahoma City
country: United States
facility: McBride Clinic
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Medford
country: United States
facility: Sunstone Medical Research, LLC
state: Oregon
city: Portland
country: United States
facility: Summit Research Network (Oregon), Inc.
state: Oregon
city: Altoona
country: United States
facility: Allegheny Pain Management
state: Pennsylvania
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, PC
state: Pennsylvania
city: Bridgeville
country: United States
facility: Paramount Clinical Research
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: CRI Worldwide LLC
state: Pennsylvania
city: Cranston
country: United States
facility: New England Center for Clinical Research
state: Rhode Island
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Columbia
country: United States
facility: Columbia Arthritis Center, P.A.
state: South Carolina
city: Columbia
country: United States
facility: Southern Orthopaedic Sports Medicine
state: South Carolina
city: Greer
country: United States
facility: Radiant Research
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Germantown
country: United States
facility: SCRI Research Center
state: Tennessee
city: Germantown
country: United States
facility: Wolf River Medical Group, LLC
state: Tennessee
city: Johnson City
country: United States
facility: Advanced Therapeutics, Inc.
state: Tennessee
city: Johnson City
country: United States
facility: Johnson City Internal Medicine
state: Tennessee
city: Austin
country: United States
facility: Capitol Medical Clinic
state: Texas
city: Austin
country: United States
facility: Walter F. Chase, MD, PA
state: Texas
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Austin
country: United States
facility: FutureSearch Trials
state: Texas
city: Beaumont
country: United States
facility: DiscoveResearch, Inc.
state: Texas
city: Bryan
country: United States
facility: DiscoveResearch, Incorporated
state: Texas
city: Carrollton
country: United States
facility: Trinity Hypertension & Metabolic Research Institute Punzi Medical Center
state: Texas
city: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Houston
country: United States
facility: Advances In Health, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Research, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Research
state: Texas
city: Nassau Bay
country: United States
facility: Centex Research
state: Texas
city: San Antonio
country: United States
facility: Office of Theresia Lee, MD
state: Texas
city: San Antonio
country: United States
facility: Paragon Research Center
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research, PA
state: Texas
city: Salt Lake City
country: United States
facility: Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: Foothill Family Clinic
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Norfolk
country: United States
facility: National Clinical Research - Norfolk, Inc.
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research, Incorporated
state: Virginia
city: Virginia Beach
country: United States
facility: Advanced Pain Management
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.