Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study

Abstract

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.

Conflict of interest statement

Disclosure

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. DMA, TJB and GJB are co-inventors on relevant patents with all rights and royalties assigned to MassBiologics; GJB, TJB, DMA, BL ML, HLS, DCM are current or former employees of MassBiologics; RTC, FDG, MPC, TDS, SE received research support from MassBiologics; RTC (Grant: Merck, Gilead, Pfizer, Romark); FDG (Consulting: Merck, Vertex; Grant: Merck; Speaking and Teaching: Merck); TDS (Advisory Committees or Review Panels: Vertex, Salix, Merck, Gilead); DMA spouse is stockholder, Merck.

The authors JM, MH, JJP, EAP, SF, MS, RWF, GS, PDZ, UK have no conflicts of interest to disclosure as described by the American Journal of Transplantation.

© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

Figure 1

Study Flow Chart

Figure 2

Serum HCV RNA concentrations in study subjects during the first week after LT (A) and during the 56 day study period (B). Blue lines indicate antibody-treated subjects and red lines indicate placebo-treated subjects. Solid lines represent mean concentrations and dotted lines represent individual subjects.

Figure 2

Serum HCV RNA concentrations in study subjects during the first week after LT (A) and during the 56 day study period (B). Blue lines indicate antibody-treated subjects and red lines indicate placebo-treated subjects. Solid lines represent mean concentrations and dotted lines represent individual subjects.

Figure 3

Median change in HCV RNA from baseline during the 56 day study period.

Figure 4

Mean antibody concentrations to MBL-HCV1 epitope measured during the first week post LT (A) and during the 56 day study period (B) in antibody-treated subjects. Error bars represent standard deviation.

Figure 4

Mean antibody concentrations to MBL-HCV1 epitope measured during the first week post LT (A) and during the 56 day study period (B) in antibody-treated subjects. Error bars represent standard deviation.