A Study of Tanezumab in Adults With Chronic Low Back Pain

• ClinicalTrials.gov Identifier: NCT00876187
• Recruitment Status: Completed
• First Posted: April 6, 2009
• Last Update Posted: July 22, 2011
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: April 3, 2009
• First Posted Date: April 6, 2009
• Last Update Posted Date: July 22, 2011
• Study Start Date: June 2009
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2009)

• Change from Baseline to Week 16 in the daily Low Back Pain Intensity (LBPI) as measured by an 11-point Numeric Rating Scale (NRS) for tanezumab vs placebo treatment [ Time Frame: Week 16 ]
• Change from Baseline to Week 16 in the daily average LBPI score for tanezumab vs. naproxen [ Time Frame: Week 16 ]

• Original Primary Outcome Measures (submitted: April 3, 2009): Change from Baseline to Week 16 in the daily Low Back Pain Intensity (LBPI) as measured by an 11-point Numeric Rating Scale (NRS) for tanezumab vs placebo treatment [ Time Frame: Week 16 ]

Current Secondary Outcome Measures (submitted: October 20, 2009)

• Change from Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) total score for tanezumab vs placebo [ Time Frame: Week 16 ]
• Change from Baseline to Week 16 in the Patient Global Assessment of Low Back Pain score for tanezumab vs placebo [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, and 12 in the LBPI NRS score. [ Time Frame: Week 16 ]
• Percent change from Baseline in the LBPI NRS score to Week 16. [ Time Frame: Week 16 ]
• Response as defined by a ≥30% and a ≥50% reduction from Baseline in the daily LBPI NRS score at Weeks 2, 4, 8, 12, and 16. [ Time Frame: Week 16 ]
• Total duration of response as defined by days with a ≥30% and a ≥50% reduction from Baseline in the daily average LBPI NRS score. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12, and 16 in the Brief Pain Inventory short form (BPI sf) scores for Worst Pain and Average Pain. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12 and 16 (for tanezumab vs. naproxen) in RMDQ total score. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12, and 16 in the BPI sf score for the Pain Interference Index (composite function score), Pain Interference with General Activity, with Walking Ability, with Sleep, and with Normal Work. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12 and 16 (for tanezumab vs. naproxen) in PGA of Low Back Pain score. [ Time Frame: Week 16 ]
• Time to discontinuation due to lack of efficacy. [ Time Frame: Week 16 ]
• Chronic Low Back Pain Responder Index analysis [composite endpoint of Low Back Pain Intensity (NRS) score, PGA of Low Back Pain (disease activity), and RMDQ total score] at Weeks 2, 4, 8, 12, and 16 [ Time Frame: Week 16 ]
• Incidence of patients, number of days, and amount of rescue medication use during Weeks 2, 4, 8, 12, and 16; [ Time Frame: Week 16 ]
• Safety measures: Adverse events; Safety laboratory testing (chemistry, hematology, urinalysis); Electrocardiogram (ECG); Neurological exam (Neuropathy Impairment Score [NIS]); Physical examinations; Vital signs. [ Time Frame: Week 24 ]
• Anti Drug Antibody (ADA) assessments at Baseline, and predose at Weeks 8, 16, and 24; [ Time Frame: Week 24 ]
• Measurement of plasma tanezumab concentrations (PK) at Baseline (predose and postdose), Week 4, predose and postdose at Week 8, and at Weeks 16 and 24; [ Time Frame: Week 24 ]
• Measurement of total and bound NGF at Baseline (predose and postdose), Week 4, predose and postdose at Week 8, and at Weeks 16 and 24. [ Time Frame: Week 24 ]
• Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) change from Baseline to Weeks 8 and 16 in the percent work time missed and other measures of productivity impairment due to CLBP. [ Time Frame: Week 16 ]

Original Secondary Outcome Measures (submitted: April 3, 2009)

• Change from Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) total score for tanezumab vs placebo [ Time Frame: Week 16 ]
• Change from Baseline to Week 16 in the Patient Global Assessment of Low Back Pain score for tanezumab vs placebo [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12 and 16 (for tanezumab vs. naproxen only) in the LBPI NRS score. [ Time Frame: Week 16 ]
• Percent change from Baseline in the LBPI NRS score through Week 16. [ Time Frame: Week 16 ]
• Response as defined by a ≥30% and a ≥50% reduction from Baseline in the daily LBPI NRS score at Weeks 2, 4, 8, 12, and 16. [ Time Frame: Week 16 ]
• Time to a ≥30% and a ≥50% reduction from Baseline in the daily average LBPI NRS score. [ Time Frame: Week 16 ]
• Total duration of response as defined by days with a ≥30% and a ≥50% reduction from Baseline in the daily average LBPI NRS score. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12, and 16 in the Brief Pain Inventory short form (BPI sf) scores for Worst Pain and Average Pain. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12 and 16 (for tanezumab vs. naproxen) in RMDQ total score. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12, and 16 in the BPI sf score for the Pain Interference Index (composite function score), Pain Interference with General Activity, Pain Interference with Walking Ability, Pain Interference with Sleep, and Pain [ Time Frame: Week 16 ]
• Interference with Normal Work. [ Time Frame: Week 16 ]
• Change from Baseline to Weeks 2, 4, 8, 12 and 16 (for tanezumab vs. naproxen) in PGA of Low Back Pain score. [ Time Frame: Week 16 ]
• Incidence of withdrawal due to lack of efficacy. [ Time Frame: Week 16 ]
• Chronic Low Back Pain Responder Index analysis [composite endpoint of Low Back Pain Intensity (NRS) score, PGA of Low Back Pain (disease activity), and RMDQ total score] at Weeks 2, 4, 8, 12, and 16; • Work Productivity and Activity Impairment [ Time Frame: Week 16 ]
• Questionnaire: Specific Health Problem (WPAI:SHP) change from Baseline to Weeks 8 and 16 in the percent work time missed due to CLBP, percent impairment while working due to CLBP, percent overall work impairment due to CLBP, and percent activity [ Time Frame: Week 16 ]
• impairment due to CLBP. [ Time Frame: Week 16 ]
• Incidence of patients, number of days, and amount of rescue medication use during Weeks 2, 4, 8, 12, and 16; [ Time Frame: Week 16 ]
• Safety measures: Adverse events; Safety laboratory testing (chemistry, hematology, urinalysis); Electrocardiogram (ECG); Neurological exam (Neuropathy Impairment Score [NIS]); Physical examinations; Vital signs. [ Time Frame: Week 24 ]
• Anti Drug Antibody (ADA) assessments at Baseline, and predose at Weeks 8, 16, and 24; [ Time Frame: Week 24 ]
• Measurement of plasma tanezumab concentrations (PK) at Baseline (predose and postdose), Week 4, predose and postdose at Week 8, and at Weeks 16 and 24; [ Time Frame: Week 24 ]
• Measurement of total and bound NGF at Baseline (predose and postdose), Week 4, predose and postdose at Week 8, and at Weeks 16 and 24. [ Time Frame: Week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Low Back Pain

Intervention

• 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
• Biological: Tanezumab 10 mg IV
  2 IV administrations of tanezumab 10 mg at an 8 week interval
• Biological: Tanezumab 5 mg IV
  2 IV administrations of tanezumab 5 mg at an 8 week interval
• 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

Study Arms

• Experimental: Tanezumab 20 mg IV
  Interventions:

  • Biological: Tanezumab 20 mg IV
  • Drug: Placebo for naproxen
• Experimental: Tanezumab 10 mg IV
  Interventions:

  • Biological: Tanezumab 10 mg IV
  • Drug: Placebo for naproxen
• Experimental: Tanezumab 5 mg IV
  Interventions:

  • Biological: Tanezumab 5 mg IV
  • Drug: Placebo for naproxen
• Active Comparator: Naproxen
  Interventions:

  • Biological: Placebo for tanezumab
  • Drug: Naproxen
• Placebo Comparator: Placebo
  Interventions:

  • Biological: Placebo for tanezumab
  • Drug: Placebo for naproxen

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 16, 2010): 1359
• Original Estimated Enrollment (submitted: April 3, 2009): 1000
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00876187
• Other Study ID Numbers: A4091012
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2011