First Administration to Humans of a Monoclonal Antibody Cocktail Against Rabies Virus: Safety, Tolerability, and Neutralizing Activity

Authors

A.B.H. Bakker, Crucell Holland BV, Leiden, The Netherlands
C. Python, Crucell, Berna Biotech Ltd., Bern, Switzerland
C.J. Kissling, MDS Pharma Services, Lincoln, NE, USA
P. Pandya, RelClin, Reliance Clinical Pharmacology and Pharmacokinetic Facility, Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, India
W.E. Marissen, Crucell Holland BV, Leiden, The Netherlands
M.F. Brink, Crucell Holland BV, Leiden, The Netherlands
F. Lagerwerf, Crucell Holland BV, Leiden, The Netherlands
S. Worst, Crucell Holland BV, Leiden, The Netherlands
E. van Corven, Crucell Holland BV, Leiden, The Netherlands
S. Kostense, Crucell Holland BV, Leiden, The Netherlands
K. Hartmann, Crucell, Berna Biotech Ltd., Bern, Switzerland
G.J. Weverling, Crucell Holland BV, Leiden, The Netherlands
F. Uytdehaag, Crucell Holland BV, Leiden, The Netherlands
C. Herzog, Crucell, Berna Biotech Ltd., Bern, Switzerland
D.J. Briggs, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
C.E. Rupprecht, Rabies Section, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USAFollow
R. Grimaldi, Crucell Holland BV, Leiden, The Netherlands
J. Goudsmit, Crucell Holland BV, Leiden, The Netherlands

Date of this Version

2008

Comments

Published in Vaccine 26 (2008) 5922–5927.

Abstract

Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies.
The studies included healthy adult subjects in the USA and India and involved two parts. First, subjects received a single intramuscular dose of CL184 or placebo in a double blind, randomized, dose-escalation trial. Second, open-label CL184 (20 IU/kg)was co-administered with rabies vaccine. Safety was the primary objective and rabies virus neutralizing activity (RVNA) was investigated as efficacy parameter.
Pain at the CL184 injection site was reported by less than 40% of subjects; no fever or local induration, redness or swelling was observed. RVNA was detectable from day 1 to day 21 after a single dose of CL184 20 or 40 IU/kg. All subjects had adequate (>0.5 IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP.