Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.
Department of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
R T
RT
Chung
Department of Transplantation, Lahey Clinic Medical Center, Burlington, MA.
F D
FD
Gordon
Beth Israel Deaconess Medical Center, Boston, MA.
M P
MP
Curry
Department of Surgery, Mount Sinai Medical Center, New York, NY.
T D
TD
Schiano
Department of Medicine, Yale New Haven Hospital, New Haven, CT.
S
S
Emre
Department of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
K
K
Corey
Department of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
J F
JF
Markmann
Department of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
M
M
Hertl
Department of Transplantation, Lahey Clinic Medical Center, Burlington, MA.
J J
JJ
Pomposelli
Department of Transplantation, Lahey Clinic Medical Center, Burlington, MA.
E A
EA
Pomfret
Department of Surgery, Mount Sinai Medical Center, New York, NY.
S
S
Florman
Department of Medicine, Yale New Haven Hospital, New Haven, CT.
M
M
Schilsky
MassBiologics, University of Massachusetts Medical School, Boston, MA.
T J
TJ
Broering
Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
R W
RW
Finberg
Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
G
G
Szabo
Howard Hughes Medical Institute and Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA.
P D
PD
Zamore
Department of Transplantation, Lahey Clinic Medical Center, Burlington, MA.
U
U
Khettry
MassBiologics, University of Massachusetts Medical School, Boston, MA.
G J
GJ
Babcock
MassBiologics, University of Massachusetts Medical School, Boston, MA.
D M
DM
Ambrosino
MassBiologics, University of Massachusetts Medical School, Boston, MA.
B
B
Leav
MassBiologics, University of Massachusetts Medical School, Boston, MA.
M
M
Leney
MassBiologics, University of Massachusetts Medical School, Boston, MA.
H L
HL
Smith
MassBiologics, University of Massachusetts Medical School, Boston, MA.
D C
DC
Molrine
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001706:Biopsy; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus