A Phase II Open-Label Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) Combined With Oral Direct-Acting Antivirals in Hepatitis C Infected Patients Undergoing Liver Transplantation

The purpose of this study is to assess efficacy of a human monoclonal antibody against Hepatitis C (MBL-HCV1) combined with telaprevir [part 1: an HCV protease inhibitor] or sofosbuvir [part 2: an Hepatitis C virus NS5B polymerase inhibitor] in a 56 day treatment duration in patients undergoing liver transplantation due to chronic HCV infection. There is an option for extended study treatment through 84 days if viral load is undetectable at day 56.

开始日期2012-11-21

申办/合作机构

MassBiologics

NCT01121185 / Terminated临床2期

A Phase II Randomized, Double-Blind, Placebo Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) in Hepatitis C Infected Patients Undergoing Liver Transplantation

The purpose of this study is to determine whether a human monoclonal antibody against Hepatitis C (MBL-HCV1) is effective in preventing detectable levels of Hepatitis C virus in patients undergoing liver transplantation due to chronic HCV infection. The study will also determine if MBL-HCV1 is effective in delaying or reducing the amount of detectable HCV in patients after transplant.

开始日期2010-06-01

申办/合作机构

MassBiologics

NCT00952263 / Completed临床1期

Open-Label, Dose Escalation Phase I Study in Healthy Volunteers to Evaluate the Safety and Pharmacokinetics of a Human Monoclonal Antibody (MBL-HCV1) Against Hepatitis C E2 Glycoprotein

This is a phase I, open-label, dose escalation study to evaluate the safety of MBL-HCV1 in healthy adult volunteers. Eligible volunteers will be admitted to a phase 1 unit for study infusion. A single dose of human monoclonal antibody will be administered. The study duration is 56 days. During this time, safety will be assessed via physical examinations, laboratory testing, concomitant medication usage and review of treatment emergent adverse events should they occur. Pharmacokinetics will be derived from analysis of blood samples obtained during the 56 day study.

开始日期2009-07-01

申办/合作机构

MassBiologics

100 项与 MBL-HCV1 相关的临床结果

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100 项与 MBL-HCV1 相关的转化医学

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100 项与 MBL-HCV1 相关的专利（医药）

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项与 MBL-HCV1 相关的文献（医药）

2013-04-01·American Journal of Transplantation1区 · 医学

Human Monoclonal Antibody MBL-HCV1 Delays HCV Viral Rebound Following Liver Transplantation: A Randomized Controlled Study

1区 · 医学

Article

作者: Hertl, M ; Gordon, F D ; Markmann, J F ; Ambrosino, D M ; Khettry, U ; Finberg, R W ; Zamore, P D ; Curry, M P ; Leney, M ; Schilsky, M ; Broering, T J ; Leav, B ; Florman, S ; Chung, R T ; Pomposelli, J J ; Babcock, G J ; Molrine, D C ; Szabo, G ; Schiano, T D ; Corey, K ; Emre, S ; Smith, H L ; Pomfret, E A

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.

PLoS ONE3区 · 综合性期刊

High-Throughput Sequencing Analysis of Post-Liver Transplantation HCV E2 Glycoprotein Evolution in the Presence and Absence of Neutralizing Monoclonal Antibody

3区 · 综合性期刊

ArticleOA

作者: Phillip D. Zamore ; Donna M. Ambrosino ; Heidi L. Smith ; Zhiping Weng ; Deborah C. Molrine ; Yang Wang ; Sowmya Iyer ; Brian G. Pierce ; Kirk Rowley ; Gregory J. Babcock

Chronic hepatitis C virus (HCV) infection is the most common cause of end-stage liver disease, often leading to liver transplantation, in which case circulating virions typically infect the transplanted liver within hours and viral concentrations can quickly exceed pre-transplant levels. MBL-HCV1 is a fully human monoclonal antibody recognizing a linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423). The ability of MBL-HCV1 to prevent HCV recurrence after liver transplantation was investigated in a phase 2 randomized clinical trial evaluating six MBL-HCV1-treated subjects and five placebo-treated subjects. MBL-HCV1 treatment significantly delayed time to viral rebound compared with placebo treatment. Here we report results from high-throughput sequencing on the serum of each of the eleven enrolled subjects prior to liver transplantation and after viral rebound. We further sequenced the sera of the MBL-HCV1-treated subjects at various interim time points to study the evolution of antibody-resistant viral variants. We detected mutations at one of two positions within the antibody epitope--mutations of N at position 415 to D, K or S, or mutation of N at position 417 to S. It has been previously reported that N415 is not glycosylated in the wild-type E2 protein, but N417S can lead to glycosylation at position 415. Thus N415 is a key position for antibody recognition and the only routes we identified for viral escape, within the constraints of HCV fitness in vivo, involve mutating or glycosylating this position. Evaluation of mutations along the entire E1 and E2 proteins revealed additional positions that changed moderately before and after MBL-HCV1 treatment for subsets of the six subjects, yet underscored the relative importance of position 415 in MBL-HCV1 resistance.

100 项与 MBL-HCV1 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
丙型肝炎	临床2期	美国	MassBiologics	2012-11-21

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01532908 (MBL-HCV1, CTgov)	临床2期	丙型肝炎	11	MBL-HCV1+Telaprevir (Part 1) (Part 1: MBL-HCV1 and Telaprevir)	鏇鏇積鏇壓襯遞夢構遞(醖醖蓋窪繭積窪壓窪鑰) = 膚壓鬱醖鏇鑰遞淵艱獵觸憲獵鏇淵鹽鬱憲襯鬱 (餘糧願蓋鏇憲積鏇膚範, 齋範窪窪鬱鑰簾鑰鹽願 ~ 範艱淵範餘獵襯製顧醖) 更多	-	2021-02-05
				Sofosbuvir (Part 2)+MBL-HCV1 (Part 2: MBL-HCV1 and Sofosbuvir)	鏇鏇積鏇壓襯遞夢構遞(醖醖蓋窪繭積窪壓窪鑰) = 憲簾選獵鏇襯夢鹽膚壓觸憲獵鏇淵鹽鬱憲襯鬱 (餘糧願蓋鏇憲積鏇膚範, 衊構製簾簾壓鑰願鬱遞 ~ 壓夢鑰觸糧獵餘膚齋夢) 更多
NCT01121185 (Pubmed \| MMWR Morb Mortal Wkly Rep)	临床2期	-	11	MBL-HCV1	(窪範積築鑰選襯構憲願) = 衊繭製餘夢廠衊積鹹夢觸範鏇製構製顧簾遞艱 (鑰構築鹹膚齋壓襯鬱選 ) 更多	-	2013-04-01
				Placebo	(窪範積築鑰選襯構憲願) = 製艱鹹鏇壓願齋鹹鹹願觸範鏇製構製顧簾遞艱 (鑰構築鹹膚齋壓襯鬱選 ) 更多