title: Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients.
abstract: Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R-) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and 35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%; P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum-adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030). Adverse events were generally balanced between treatment groups. In high-risk kidney transplant recipients, RG7667 was well tolerated, numerically reduced the incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to CMV viremia, and was associated with less CMV disease than the placebo. (This study has been registered at ClinicalTrials.gov under registration no. NCT01753167.).
authors.affiliation: 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: Henry Ford Transplant Institute, Detroit, Michigan, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Department of Nephrology and Clinical Immunology, CHRU de Tours and EA 4245, University François Rabelais, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gatault
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: McBride
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: Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Snydman
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Brinda
authors.initials: B
authors.lastname: Emu
authors.affiliation: Genentech, Inc., South San Francisco, 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: 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.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Rosenberger
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Gennaro
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Natalee S
authors.initials: NS
authors.lastname: Striano
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: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D014766:Viremia / Q000517:prevention & control / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D010919:Placebos; C000623144:RG7667
keywords: cytomegalovirus; kidney transplantation; monoclonal antibodies