A Study of Tanezumab in Adults With Chronic Low Back Pain

• 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

• 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

• 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.

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.