title: Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults.
abstract: Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n = 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n = 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n = 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.).
authors.affiliation: Genentech, Inc., South San Francisco, California, USA Department of Medicine, Division of Nephrology, University of California, San Francisco, California, USA.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Ishida
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Burgess
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Derby
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Pearline A
authors.initials: PA
authors.lastname: Brown
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Maia
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.affiliation: Genentech, Inc., South San Francisco, California, USA Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven Connecticut, USA.
authors.forename: Brinda
authors.initials: B
authors.lastname: Emu
authors.affiliation: Genentech, Inc., South San Francisco, California, USA Gilead Sciences, Inc., Foster City, California, USA.
authors.forename: Becket
authors.initials: B
authors.lastname: Feierbach
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Fouts
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: X Charlene
authors.initials: XC
authors.lastname: Liao
authors.affiliation: Genentech, Inc., South San Francisco, California, USA tavel.jorge@gene.com.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Tavel
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; C000623144:RG7667