HCV Infection, Liver Transplantation
Conditions
Keywords
Hepatitis C virus (HCV), Liver transplantation, Human Monoclonal Antibody
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.
Interventions
BIOLOGICALMBL-HCV1
50 mg/kg MBL-HCV1, intravenous
OTHER0.9% Sodium chloride Placebo
0.9% sodium chloride, intravenous
Sponsors
MassBiologics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation | At Day 42 post-transplantation | Serum HCV RNA was measured by Quantitative RT-PCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | 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 | Baseline Day 0 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) | Through Day 56 | 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. |
| The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Through Day 56 | 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) |
| Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Through Day 56 | 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 | Through Day 56 | Serum HCV RNA was measured by Quantitative RT-PCR |
| Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Through Day 56 | 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. |
Countries
United States
Participant flow
Recruitment details
Patients with HCV genotype 1a infection scheduled to undergo liver transplantation were recruited at 8 U.S. transplantation centers between June 2010 and April 2011. Due to slower than anticipated subject accrual, enrollment was stopped after 13 subjects were randomized; 11 underwent liver transplantation and received the study intervention.
Pre-assignment details
Reasons for exclusion after randomization included identification of a protocol-specified exclusion criterion in the recipient or the donor at the time of organ offer or failure to undergo liver transplantation.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: MBL-HCV1 Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation. | 6 |
| Placebo Comparator: 0.9% Sodium Chloride Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation. | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not infused | 0 | 1 |
| Overall Study | Not transplanted | 1 | 0 |
Baseline characteristics
| Characteristic | Experimental: MBL-HCV1 | Placebo Comparator: 0.9% Sodium Chloride | Total |
|---|---|---|---|
| Age, Continuous | 60.9 years | 57.2 years | 59.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hepatocellular carcinoma | 4 participants | 2 participants | 6 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 9 Participants |
| Serum HCV RNA concentration | 6.07 log10 IU/mL | 5.59 log10 IU/mL | 6.03 log10 IU/mL |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 1 / 6 | 4 / 5 |
Outcome results
Primary
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Time frame: At Day 42 post-transplantation
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: MBL-HCV1 | Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation | 100 percentage of participants |
| Placebo Comparator: 0.9% Sodium Chloride | Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation | 100 percentage of participants |
Secondary
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.
Time frame: Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: MBL-HCV1 | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 14 | -2.48 log10 IU/mL |
| Experimental: MBL-HCV1 | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 42 | 0.23 log10 IU/mL |
| Experimental: MBL-HCV1 | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 28 | -0.75 log10 IU/mL |
| Experimental: MBL-HCV1 | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 3 | -3.07 log10 IU/mL |
| Placebo Comparator: 0.9% Sodium Chloride | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 28 | 1.22 log10 IU/mL |
| Placebo Comparator: 0.9% Sodium Chloride | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 14 | 0.10 log10 IU/mL |
| Placebo Comparator: 0.9% Sodium Chloride | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 3 | -1.01 log10 IU/mL |
| Placebo Comparator: 0.9% Sodium Chloride | Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation | Day 42 | 1.22 log10 IU/mL |
Secondary
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.
Time frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Screening | 74 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 0 | 76 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 1 | 565 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 2 | 501 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 3 | 374 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 4 | 301 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 5 | 243 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 6 | 207 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 7 | 163 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 14 | 38 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 21 | 34 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 28 | 21 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 42 | 22 U/L |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 56 | 41 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 21 | 55 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Screening | 114 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 6 | 219 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 0 | 107 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 42 | 174 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 1 | 404 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 7 | 176 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 2 | 415 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 28 | 109 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 3 | 464 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 14 | 54 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 4 | 355 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 56 | 183 U/L |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) | Day 5 | 253 U/L |
Secondary
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.
Time frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Screening | 1.5 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 0 | 1.6 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 1 | 1.4 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 2 | 1.2 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 3 | 1.2 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 4 | 1.5 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 5 | 1.6 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 6 | 1.4 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 7 | 1.3 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 14 | 1.2 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 21 | 2 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 28 | 1.6 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 42 | 1.2 unitless |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 56 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 21 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Screening | 1.5 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 6 | 1.2 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 0 | 1.5 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 42 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 1 | 1.3 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 7 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 2 | 1.3 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 28 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 3 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 14 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 4 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 56 | 1.1 unitless |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) | Day 5 | 1.1 unitless |
Secondary
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 frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Screening | 2.8 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 0 | 2.6 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 1 | 3.3 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 2 | 2.3 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 3 | 2 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 4 | 2 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 5 | 2.1 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 6 | 2.6 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 7 | 3 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 14 | 1.2 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 21 | 1 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 28 | 0.9 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 42 | 0.8 mg/dL |
| Experimental: MBL-HCV1 | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 56 | 0.7 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 21 | 1.7 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Screening | 8.9 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 6 | 8.3 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 0 | 2.9 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 42 | 1.2 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 1 | 4.7 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 7 | 8.2 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 2 | 4.1 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 28 | 1.5 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 3 | 4.7 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 14 | 2.6 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 4 | 5.5 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 56 | 2 mg/dL |
| Placebo Comparator: 0.9% Sodium Chloride | Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin | Day 5 | 7 mg/dL |
Secondary
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.
Time frame: Baseline Day 0 and Day 42
Population: The 11 subjects who were randomized, initiated study infusions, and underwent transplantation were included in the analysis population. On day 0, all subjects had pre-transplant biopsy specimens available for analysis. On day 42, 4 subjects in the MBL-HCV1 group and 5 subjects in the placebo group had biopsy specimens available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: MBL-HCV1 | Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 | Day 0 | 0.0 Histologic activity index (HAI) score |
| Experimental: MBL-HCV1 | Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 | Day 42 | 0.6 Histologic activity index (HAI) score |
| Placebo Comparator: 0.9% Sodium Chloride | Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 | Day 0 | 1.0 Histologic activity index (HAI) score |
| Placebo Comparator: 0.9% Sodium Chloride | Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 | Day 42 | 4.0 Histologic activity index (HAI) score |
Secondary
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)
Time frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Nervous System Disorders | 7 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Psychiatric Disorders | 3 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Metabolism And Nutrition Disorders | 7 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Vascular Disorders | 2 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Skin And Subcutaneous Tissue Disorders | 3 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Blood And Lymphatic System Disorders | 1 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Gastrointestinal Disorders | 9 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Infections And Infestations | 1 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Injury, Poisoning And Procedural Complications | 4 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Eye Disorders | 1 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Investigations | 16 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Musculoskeletal And Connective Tissue Disorders | 2 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Respiratory, Thoracic And Mediastinal Disorders | 3 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Hepatobiliary Disorders | 1 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | General Disorders And Administration Site Conditio | 13 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Reproductive System And Breast Disorders | 1 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Renal And Urinary Disorders | 4 events |
| Experimental: MBL-HCV1 | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Ear And Labyrinth Disorders | 0 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Renal And Urinary Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | General Disorders And Administration Site Conditio | 6 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Gastrointestinal Disorders | 9 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Metabolism And Nutrition Disorders | 10 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Investigations | 7 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Nervous System Disorders | 3 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Skin And Subcutaneous Tissue Disorders | 4 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Injury, Poisoning And Procedural Complications | 3 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Respiratory, Thoracic And Mediastinal Disorders | 2 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Ear And Labyrinth Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Psychiatric Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Vascular Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Blood And Lymphatic System Disorders | 2 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Infections And Infestations | 9 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Eye Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Musculoskeletal And Connective Tissue Disorders | 1 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Hepatobiliary Disorders | 0 events |
| Placebo Comparator: 0.9% Sodium Chloride | The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation | Reproductive System And Breast Disorders | 0 events |
Secondary
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Time frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: MBL-HCV1 | Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation | NA days |
| Placebo Comparator: 0.9% Sodium Chloride | Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation | NA days |
Post Hoc
Time To Viral Rebound Post-Transplantation(Serum HCV RNA Increased ≥ 1 log10 From Viral Nadir)
The time of viral rebound was defined as the time of the first measurement of serum HCV RNA increased ≥ 1 log10 from the viral nadir (the lowest serum HCV RNA level post-transplantation). Serum HCV RNA was measured by RT-PCR.
Time frame: Through Day 56
Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental: MBL-HCV1 | Time To Viral Rebound Post-Transplantation(Serum HCV RNA Increased ≥ 1 log10 From Viral Nadir) | 22.7 days |
| Placebo Comparator: 0.9% Sodium Chloride | Time To Viral Rebound Post-Transplantation(Serum HCV RNA Increased ≥ 1 log10 From Viral Nadir) | 2.33 days |