Analgesic Efficacy And Safety of Tanezumab Added On To Diclofenac SR In Patients With Osteoarthritis Of The Knee Or Hip

• Biological: tanezumab
  IV tanezumab 10 mg every 8 weeks (through Week 16)
• Drug: diclofenac
  Oral diclofenac SR 75 mg BID for 32 weeks
• Biological: tanezumab
  IV tanezumab 5 mg every 8 weeks (through Week 16)
• Biological: tanezumab
  IV tanezumab 2.5 mg every 8 weeks (through Week 16)
• Other: IV placebo
  IV placebo to match tanezumab every 8 weeks (through Week 16)

• Experimental: Tanezumab 10 mg + diclofenac
  IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
  Interventions:

  • Biological: tanezumab
  • Drug: diclofenac
• Experimental: Tanezumab 5 mg + diclofenac
  IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
  Interventions:

  • Biological: tanezumab
  • Drug: diclofenac
• Experimental: Tanezumab 2.5 mg + diclofenac
  IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
  Interventions:

  • Biological: tanezumab
  • Drug: diclofenac
• Placebo Comparator: IV placebo + diclofenac
  IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
  Interventions:

  • Drug: diclofenac
  • Other: IV placebo

• 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.
• Balanescu AR, Feist E, Wolfram G, Davignon I, Smith MD, Brown MT, West CR. Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial. Ann Rheum Dis. 2014 Sep;73(9):1665-72. doi: 10.1136/annrheumdis-2012-203164. Epub 2013 Jul 12.

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 diclofenac 150 mg/day and be tolerating their diclofenac regimen.
• Pain and function levels as required by the protocol at Screening and Baseline.
• Willing to discontinue all non-study pain medications throughout 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.
• History of other disease that may involve index knee or hip including inflammatory joint diseases, chrystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis (RA), joint infections, neuropathic disorders, avascular necrosis, Paget's disease or tumors.
• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with OA.
• Signs and symptoms of clinically significant cardiac disease within 6 months prior to screening.
• Diagnosis or 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 150 micro-mol/L in men or 133 micro-mol/L in women.
• Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to Screening.
• Known hypersensitivity to NSAIDs (eg, diclofenac), cyclooxygenase inhibitors or paracetamol (acetaminophen).