Long-Term Analgesic Efficacy And Safety Of Tanezumab Alone Or In Combination With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Versus NSAIDs Alone In Patients With Osteoarthritis Of The Knee Or Hip

• Osteoarthritis
• Arthritis

• Drug: NSAID
  IV doses of placebo (to match tanezumab) every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
• Biological: tanezumab
  IV tanezumab 5 mg every 8 weeks (through Week 48) and oral placebo for NSAID BID from Weeks 2 through 56
• Biological: tanezumab
  IV tanezumab 10 mg every 8 weeks (through Week 56) and oral placebo for NSAID BID from Weeks 2 through 56
• Biological: tanezumab
  IV tanezumab 5 mg every 8 weeks (through Week 48)
• Drug: NSAID
  Oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
• Biological: tanezumab
  IV tanezumab 10 mg every 8 weeks (through Week 48)

• Active Comparator: IV Placebo + NSAID
  Oral NSAID
  Intervention: Drug: NSAID
• Experimental: Tanezumab 5 mg
  IV tanezumab 5 mg every 8 weeks (through Week 48)
  Intervention: Biological: tanezumab
• Experimental: Tanezumab 10 mg
  IV tanezumab 10 mg every 8 weeks (through Week 48)
  Intervention: Biological: tanezumab
• Experimental: Tanezumab 5 mg + NSAID
  IV doses of tanezumab 5 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
  Interventions:

  • Biological: tanezumab
  • Drug: NSAID
• Experimental: Tanezumab 10 mg + NSAID
  IV doses of tanezumab 10 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
  Interventions:

  • Biological: tanezumab
  • Drug: NSAID

• 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.
• 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.
• Schnitzer TJ, Ekman EF, Spierings EL, Greenberg HS, Smith MD, Brown MT, West CR, Verburg KM. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann Rheum Dis. 2015 Jun;74(6):1202-11. doi: 10.1136/annrheumdis-2013-204905. Epub 2014 Mar 13.

Inclusion Criteria:

• Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence x-ray grade equal to, or greater than, 2.
• Patients must be experiencing some benefit from their current stable dose regimen of oral NSAID therapy of either naproxen 500-1000 mg/day or celecoxib 200 mg/day (either 100 mg BID or 200 mg QD) and be tolerating their NSAID regimen.
• Pain level and function levels as required by the protocol at Screening and Baseline.
• Willing to discontinue all non-study pain medications for osteoarthritis except rescue medication (acetaminophen) and not use prohibited pain medications throughout the duration of the study except as permitted per protocol.
• Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

• Pregnant women.
• BMI greater than 39.
• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to sever pain that may confound assessments or self-evaluation of the pain associated with OA.
• Signs and symptoms of clinically significant cardiac disease with 6 months prior to screening.
• Diagnosis of TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
• History, diagnosis, signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
• At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 1.7 mg/dL (men) or 1.5 mg/dL (women).
• Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to screening.
• Known hypersensitivity to NSAIDs or cyclooxygenase inhibitors.