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Antimicrobial Agents and Chemotherapy, March 2005, p. 959-962, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.959-962.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Open-Label, Dose Escalation Study of the Safety and Pharmacokinetic Profile of Tefibazumab in Healthy Volunteers

Sandra Reilley,1 Eric Wenzel,2 Laurie Reynolds,3 Beth Bennett,2* Joseph M. Patti,2 and Seth Hetherington2

Northwest Kinetics, Tacoma, Washington,1 GloboMax, Hanover, Maryland; and Inhibitex, Inc.,3 Alpharetta, Georgia2

Received 9 July 2004/ Returned for modification 29 September 2004/ Accepted 9 November 2004

Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of Staphylococcus aureus infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (Cmax) of 59, 127, 252, and 492 µg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (Tmax) was 1.0 h for each dose. The mean elimination half-life (t1/2) was approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 µg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 µg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.

* Corresponding author. Mailing address: Inhibitex, Inc., 1165 Sanctuary Parkway, Suite 400, Alpharetta, GA 30004. Phone: (678) 746-1108. Fax: (678) 746-1265. E-mail: bbennett{at}inhibitex.com.

Antimicrobial Agents and Chemotherapy, March 2005, p. 959-962, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.959-962.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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