Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
A Phase 3 Placebo- and Oxycodone-Controlled Study of Tanezumab in Adults with Osteoarthritis.
Fidelholtz1, James, Tark2, Marvin, Spierings3, Egilius, Wolfram4, Gernot, Annis4, Karen, Smith4, Michael D., Brown4, Mark T.
A randomized, double-blind, placebo (PBO)- & active-controlled study, investigated efficacy & safety of tanezumab (TNZ), a humanized monoclonal antibody that specifically inhibits nerve growth factor, vs. oxycodone (OXY) continuous release as analgesic treatment for knee or hip osteoarthritis (OA).
Eligible patients had moderate to severe pain from knee or hip OA, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale score >=5, WOMAC Physical Function subscale score >=4, Patient Global Assessment of OA of 'Fair', 'Poor' or 'Very Poor', & Kellgren-Lawrence Grade of >=2 at Baseline. Patients received up to two doses of TNZ (10 or 5 mg IV in 8-week intervals), OXY (1040 mg every 12 hours; up-titrated & modified according to tolerability & pain relief) or PBO after appropriate prior analgesic pain medication washout. The primary endpoint was WOMAC Pain subscale score. The study was partially completed due to a FDA-imposed clinical hold so primary endpoint timing was amended from Week 16 to Week 8 to maximize planned analyses. Primary efficacy comparisons of TNZ vs. PBO were made in the intent-to-treat population (ITT; patients who received >=1 IV injection) whereas comparisons of TNZ vs. OXY & OXY vs. PBO were conducted on the modified intent-to-treat population (mITT; all ITT patients with Week 8 visit or discontinued on or before clinical hold). Incidence of adverse events (AEs) was assessed.
Both TNZ doses (p<0.001), but not OXY (p=0.700) resulted in significant improvements in WOMAC Pain subscale vs. PBO at Week 8 (Figure). WOMAC Pain subscale improvements with TNZ 10 mg & TNZ 5 mg were also superior to OXY (p<=0.018). Overall AE rate was higher with OXY (63.3%) than TNZ (40.7 44.7%) or PBO (35.5%). AEs reported in >5% of patients were nausea, constipation, vomiting, dizziness, pruritus, & headache with OXY & arthralgia with TNZ 10 mg. Incidence of patients who discontinued due to an AE was highest with OXY (10.1%), followed by TNZ 10 mg (2.7%), PBO (1.4%), & TNZ 5 mg (1.2%). Incidence of serious AEs was similar among treatments & <3%. The AE profile for TNZ was similar to that of previous TNZ studies. Two patients in TNZ 10 mg group were reported to have osteonecrosis (ON; 2/150; 1.3%; one was reported as worsening of pre-existing ON) & underwent total joint replacement (TJR). An external adjudication committee did not confirm ON, but indicated one patient had rapidly progressing OA & the other had normally progressing OA. One additional patient in the TNZ 10 mg group, one in TNZ 5 mg and one in PBO underwent TJR not associated with an AE. One patient in the OXY group underwent TJR for an AE of OA.
Treatment with TNZ (10 mg or 5 mg) resulted in superior analgesic efficacy as measured by WOMAC Pain subscale compared to PBO & OXY. Results from this study indicate that TNZ is efficacious in the treatment of OA pain. No new safety signals were identified.
To cite this abstract, please use the following information:
Fidelholtz, James, Tark, Marvin, Spierings, Egilius, Wolfram, Gernot, Annis, Karen, Smith, Michael D., et al; A Phase 3 Placebo- and Oxycodone-Controlled Study of Tanezumab in Adults with Osteoarthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1095