title: First administration to humans of a monoclonal antibody cocktail against rabies virus: safety, tolerability, and neutralizing activity.
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 (20IU/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 40IU/kg. All subjects had adequate (>0.5IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP.
authors.affiliation: Crucell Holland BV, Leiden, The Netherlands. lex.bakker@crucell.com
authors.forename: A B H
authors.initials: AB
authors.lastname: Bakker
authors.forename: C
authors.initials: C
authors.lastname: Python
authors.forename: C J
authors.initials: CJ
authors.lastname: Kissling
authors.forename: P
authors.initials: P
authors.lastname: Pandya
authors.forename: W E
authors.initials: WE
authors.lastname: Marissen
authors.forename: M F
authors.initials: MF
authors.lastname: Brink
authors.forename: F
authors.initials: F
authors.lastname: Lagerwerf
authors.forename: S
authors.initials: S
authors.lastname: Worst
authors.forename: E
authors.initials: E
authors.lastname: van Corven
authors.forename: S
authors.initials: S
authors.lastname: Kostense
authors.forename: K
authors.initials: K
authors.lastname: Hartmann
authors.forename: G J
authors.initials: GJ
authors.lastname: Weverling
authors.forename: F
authors.initials: F
authors.lastname: Uytdehaag
authors.forename: C
authors.initials: C
authors.lastname: Herzog
authors.forename: D J
authors.initials: DJ
authors.lastname: Briggs
authors.forename: C E
authors.initials: CE
authors.lastname: Rupprecht
authors.forename: R
authors.initials: R
authors.lastname: Grimaldi
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D002460:Cell Line; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000276:immunology; D011820:Rabies virus / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D011819:Rabies Vaccines