Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study

Osteoarthritis Cartilage. 2011 Dec;19(12):1405-12. doi: 10.1016/j.joca.2011.09.006. Epub 2011 Oct 5.

Abstract

Objective: To investigate the use of tanezumab, a humanized monoclonal antibody that inhibits nerve growth factor, for the treatment of moderate to severe osteoarthritis in Japanese patients.

Design: Patients received tanezumab 10, 25, 50, 100, 200 μg/kg, or placebo and were followed for 92 or 120 days. Endpoints included the incidence of adverse events (AEs) and the change from baseline to week 8 in pain intensity and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales.

Results: Patients (n = 83) were 69% female, age 44-73 years, with a Kellgren-Lawrence X-ray grade of 2-4. At week 8, compared with placebo, tanezumab 25, 100, and 200 μg/kg improved index knee pain during walking (-18.5, -14.3, and -27.6, respectively), index knee pain in the past 24 h (-19.1, -14.6, and -24.2, respectively), current index knee pain (-16.5, -10.9, and -22.8, respectively), and the WOMAC pain (-11.5, -9.6, and -18.8, respectively), physical function (-8.7, -9.5, and -17.6, respectively), and stiffness (-20.4, -11.2, and -10.2, respectively) subscales. Overall, seven patients reported AEs of abnormal peripheral sensation: allodynia (two in the tanezumab 200 μg/kg group); paresthesia (two in the tanezumab 200 μg/kg group), dysesthesia (one in the tanezumab 200 μg/kg group); thermohypoesthesia (one in the tanezumab 100 μg/kg group), and decreased vibratory sense (one in the placebo group). All of these AEs were mild to moderate in severity and transient in nature.

Conclusions: Tanezumab was safe and generally well tolerated and may improve pain symptoms in Japanese patients with moderate to severe osteoarthritis of the knee. CLINICALTRIALS.GOV IDENTIFIER: NCT00669409.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / blood
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / drug therapy*
  • Pain Measurement / methods
  • Placebos
  • Radiography
  • Receptor, Nerve Growth Factor / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Placebos
  • Receptor, Nerve Growth Factor
  • tanezumab

Associated data

  • ClinicalTrials.gov/NCT00669409