Back to resultsStudy in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C (MBL-HCV1)
Primary Purpose
HCV Infection, Liver Transplantation
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MBL-HCV1
0.9% Sodium chloride Placebo
Sponsored by
About this trial
This is an interventional prevention trial for HCV Infection focused on measuring Hepatitis C virus (HCV), Liver transplantation, Human Monoclonal Antibody
Eligibility Criteria
Inclusion Criteria:
- Patient ≥ 18 years of age with documented chronic hepatitis C virus infection of genotype 1a undergoing liver transplantation from either a deceased donor or living donor.
- Patient or legal guardian/health care proxy must have read, understood and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained.
Exclusion Criteria:
- Positive serology for Hepatitis B surface Antigen
- Positive serology for HIV
- Pregnancy or breastfeeding
- Previous history of any organ transplant
- Planned receipt of combined organ transplant (e.g. liver and kidney)
- Receipt or planned receipt of immune globulin (IVIG) within 90 days of enrollment
- History of extrahepatic malignancy and/or receiving chemotherapy within 90 days prior to enrollment with the exception of chemoembolization for hepatocellular carcinoma
- Hepatocellular carcinoma with tumor burden outside of the Milan criteria
- History of chronic renal insufficiency or creatinine > 2.5 for ≥ six months
- Personal or family history of deep venous thrombosis or pulmonary embolism
- Receipt of liver allograft from HCV positive donor or Hepatitis B core antibody positive donor
- Receipt of liver allograft donated after cardiac death of donor
- Receipt of any antiviral agents, licensed or investigational for hepatitis C virus within 90 days prior to enrollment
- Receipt of any other investigational study product within 30 days prior to enrollment
- Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely that the patient could complete the study
Sites / Locations
- Yale-New Haven Hospital
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Lahey Clinic
- Henry Ford Health System
- Mount Sinai Hospital
- Cleveland Clinic Foundation
- Methodist Healthcare Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MBL-HCV1
0.9% sodium chloride
Arm Description
Outcomes
Primary Outcome Measures
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Secondary Outcome Measures
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation
Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Subjects were asked at scheduled study visits through day 42 whether they experienced solicited adverse reactions (fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives). In addition to these solicited adverse events, subjects were asked at all scheduled study visits through day 56 to report any other adverse events, regardless of whether the event was thought to be related to the study infusions. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 12.0)
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Serum HCV RNA was measured by quantitative RT-PCR. The change in HCV RNA from baseline was obtained by calculating the difference between the baseline pre-transplantation HCV RNA level and the HCV RNA level measured at each study visit.
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42
Liver biopsies obtained at baseline (day 0) and day 42 post-transplantation were assessed for histologic evidence of hepatitis by a pathologist blinded to treatment assignment using the Ishak modification of the Knodell histologic grading system to assign a histologic activity index (HAI) score. The HAI score consists of a sum of four components: 1) periportal or periseptal interface hepatitis; 2) confluent necrosis; 3) focal lytic necrosis, apoptosis and focal inflammation; 4) portal inflammation. The total HAI score can range from a minimum of 0 to a maximum of 18, with higher scores indicating more severe hepatic inflammation.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR)
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the INR at each time-point. The INR is the ratio of a patient's prothrombin time to a control sample, raised to the power of the ISI value (International Sensitivity Index) for the batch of tissue factor being used for the assay.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT)
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the ALT at each time-point.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the total bilirubin at each time-point.
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01121185
Brief Title
Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C
Acronym
MBL-HCV1
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to slower than anticipated subject accrual.
Study Start Date
June 2010 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MassBiologics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
This is a Phase 2, randomized, double-blind, placebo controlled study in Hepatitis C (HCV) infected patients undergoing liver transplantation. Chronically infected patients with HCV genotype 1a scheduled to receive a liver transplant from either a deceased or living donor who satisfy all study inclusion or exclusion criteria will be approached to participate. The study will be conducted in two parts to test a human monoclonal antibody against Hepatitis C (MBL-HCV1). In Part 1, sixteen eligible patients will be randomized 1:1 to receive 50 mg/kg MBL-HCV1 or 0.9% sodium chloride placebo intravenously. Eleven doses will be given during the first 14 days post transplantation. Patients will be evaluated through day 56 for safety and clinical outcomes that include measurement of anti-HCV antibodies, anti-drug antibody and HCV viral load. On study visit day 42, a liver biopsy will be performed for evaluation of hepatitis. Physical examination, vital sign measurements, emergence of adverse events and concomitant medication usage will be assessed at scheduled visits and as needed during the 56 day study period.
The Data Safety and Monitoring Board will perform a futility analysis after the first 16 patients have been enrolled and completed study follow-up through study visit day 42 post transplant. Based on the results of the interim analysis, the dose of MBL-HCV1 for part 2 of the study will be determined. Part 2 of the study will be conducted in the same manner as Part 1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HCV Infection, Liver Transplantation
Keywords
Hepatitis C virus (HCV), Liver transplantation, Human Monoclonal Antibody
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MBL-HCV1
Arm Type
Experimental
Arm Title
0.9% sodium chloride
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
MBL-HCV1
Intervention Description
50 mg/kg MBL-HCV1, intravenous
Intervention Type
Other
Intervention Name(s)
0.9% Sodium chloride Placebo
Other Intervention Name(s)
Normal Saline
Intervention Description
0.9% sodium chloride, intravenous
Primary Outcome Measure Information:
Title
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
Description
Serum HCV RNA was measured by Quantitative RT-PCR
Time Frame
At Day 42 post-transplantation
Secondary Outcome Measure Information:
Title
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation
Description
Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Subjects were asked at scheduled study visits through day 42 whether they experienced solicited adverse reactions (fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives). In addition to these solicited adverse events, subjects were asked at all scheduled study visits through day 56 to report any other adverse events, regardless of whether the event was thought to be related to the study infusions. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 12.0)
Time Frame
Through Day 56
Title
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Description
Serum HCV RNA was measured by quantitative RT-PCR. The change in HCV RNA from baseline was obtained by calculating the difference between the baseline pre-transplantation HCV RNA level and the HCV RNA level measured at each study visit.
Time Frame
Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Title
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42
Description
Liver biopsies obtained at baseline (day 0) and day 42 post-transplantation were assessed for histologic evidence of hepatitis by a pathologist blinded to treatment assignment using the Ishak modification of the Knodell histologic grading system to assign a histologic activity index (HAI) score. The HAI score consists of a sum of four components: 1) periportal or periseptal interface hepatitis; 2) confluent necrosis; 3) focal lytic necrosis, apoptosis and focal inflammation; 4) portal inflammation. The total HAI score can range from a minimum of 0 to a maximum of 18, with higher scores indicating more severe hepatic inflammation.
Time Frame
Baseline Day 0 and Day 42
Title
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR)
Description
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the INR at each time-point. The INR is the ratio of a patient's prothrombin time to a control sample, raised to the power of the ISI value (International Sensitivity Index) for the batch of tissue factor being used for the assay.
Time Frame
Through Day 56
Title
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT)
Description
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the ALT at each time-point.
Time Frame
Through Day 56
Title
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin
Description
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the total bilirubin at each time-point.
Time Frame
Through Day 56
Title
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation
Description
Serum HCV RNA was measured by Quantitative RT-PCR
Time Frame
Through Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient ≥ 18 years of age with documented chronic hepatitis C virus infection of genotype 1a undergoing liver transplantation from either a deceased donor or living donor.
Patient or legal guardian/health care proxy must have read, understood and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained.
Exclusion Criteria:
Positive serology for Hepatitis B surface Antigen
Positive serology for HIV
Pregnancy or breastfeeding
Previous history of any organ transplant
Planned receipt of combined organ transplant (e.g. liver and kidney)
Receipt or planned receipt of immune globulin (IVIG) within 90 days of enrollment
History of extrahepatic malignancy and/or receiving chemotherapy within 90 days prior to enrollment with the exception of chemoembolization for hepatocellular carcinoma
Hepatocellular carcinoma with tumor burden outside of the Milan criteria
History of chronic renal insufficiency or creatinine > 2.5 for ≥ six months
Personal or family history of deep venous thrombosis or pulmonary embolism
Receipt of liver allograft from HCV positive donor or Hepatitis B core antibody positive donor
Receipt of liver allograft donated after cardiac death of donor
Receipt of any antiviral agents, licensed or investigational for hepatitis C virus within 90 days prior to enrollment
Receipt of any other investigational study product within 30 days prior to enrollment
Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely that the patient could complete the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah C. Molrine, MD
Organizational Affiliation
Massbiologics of University of Massachusetts Medical School
Official's Role
Study Director
Facility Information:
Facility Name
Yale-New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Lahey Clinic
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Methodist Healthcare Foundation
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23356386
Citation
Chung RT, Gordon FD, Curry MP, Schiano TD, Emre S, Corey K, Markmann JF, Hertl M, Pomposelli JJ, Pomfret EA, Florman S, Schilsky M, Broering TJ, Finberg RW, Szabo G, Zamore PD, Khettry U, Babcock GJ, Ambrosino DM, Leav B, Leney M, Smith HL, Molrine DC. Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study. Am J Transplant. 2013 Apr;13(4):1047-1054. doi: 10.1111/ajt.12083. Epub 2013 Jan 28.
Results Reference
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Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C
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