title: Prevention of allograft HCV recurrence with peri-transplant human monoclonal antibody MBL-HCV1 combined with a single oral direct-acting antiviral: A proof-of-concept study.
abstract: Patients with active hepatitis C virus (HCV) infection at transplantation experience rapid allograft infection, increased risk of graft failure and accelerated fibrosis. MBL-HCV1, a neutralizing human monoclonal antibody (mAb) targeting the HCV envelope, was combined with a licensed oral direct-acting antiviral (DAA) to prevent HCV recurrence post-transplant in an open-label exploratory efficacy trial. Eight subjects received MBL-HCV1 beginning on the day of transplant with telaprevir initiated between days 3 and 7 post-transplantation. Following FDA approval of sofosbuvir, two subjects received MBL-HCV1 starting on the day of transplant with sofosbuvir initiated on day 3. Combination treatment was administered for 8-12 weeks or until the stopping rule for viral rebound was met. The primary endpoint was undetectable HCV RNA at day 56 with exploratory endpoints of sustained virologic response (SVR) at 12 and 24 weeks post-treatment. Both subjects receiving mAb and sofosbuvir achieved SVR24. Four of eight subjects in the mAb and telaprevir group met the primary endpoint; one subject achieved SVR24 and three subjects relapsed 2-12 weeks post-treatment. The other four subjects experienced viral breakthrough. There were no serious adverse events related to study treatment. This proof-of-concept study demonstrates that peri-transplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.
authors.affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Smith
authors.affiliation: Department of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Liver Institute, Methodist Dallas Medical Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mantry
authors.affiliation: Division of General Surgery, Washington University, St Louis, MO, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chapman
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Recanati-Miller Transplantation Institute and The Division of Liver Diseases, The Mount Sinai Medical Center, New York, NY, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Schiano
authors.affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Boucher
authors.affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Cheslock
authors.affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Molrine
mesh_terms: D064591:Allografts; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006526:Hepatitis C / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D000075082:Proof of Concept Study; D012367:RNA, Viral / Q000097:blood; D055502:Secondary Prevention; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects; D000072230:Sustained Virologic Response; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D009842:Oligopeptides; D012367:RNA, Viral; C486464:telaprevir; D000069474:Sofosbuvir
keywords: Hepatitis C; immunoprophylaxis; liver transplantation; neutralizing antibody