Hepatitis C Infection
Conditions
Keywords
Liver Transplantation
Brief summary
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.
Detailed description
Administration of Intravenous infusions of MBL-HCV1 (50mg/kg) human monoclonal antibody during the first 14 days post-transplantation: three infusions on day 0 (1-4 hours prior to the anhepatic phase, during the anhepatic phase, and 4-12 hours post-reperfusion). Daily infusions on days 1 through 7, weekly infusions on day 14 ± 2, day 21 ± 3, and day 28 ± 3, followed by biweekly infusions on day 42 ± 3 and on day 56 ± 3 if criteria for the stopping rule are not met. For those subjects electing extended treatment, the administration of additional infusions on day 70 ± 3 and day 84 ± 3 will be performed. Subjects receive an oral direct-acting antiviral (telaprevir in Part 1 and sofosbuvir in Part 2) starting no earlier than day 3 post-transplant and no later than day 7; dosing continuing through day 56 unless criteria for the stopping rule are met. Subjects who elect to receive extended study treatment for a total of 12 weeks continue telaprevir in Part 1 or sofosbuvir in Part 2 through day 84 ± 3.
Interventions
BIOLOGICALMBL-HCV1
50 mg/kg MBL-HCV1, intravenous, up to 15 infusions over 56 days; option for extended treatment through 84 days if viral load undetectable at day 56
DRUGTelaprevir (Part 1)
Two 375 mg tablets, 3 times a day up to 56 days; option for extended treatment through 84 days if viral load undetectable at day 56
DRUGSofosbuvir (Part 2)
One 400 mg tablet, 1 time per day up to 56 days; option for extended treatment through 84 days if viral load undetectable at day 56
Sponsors
MassBiologics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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 1 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 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 * Extrahepatic malignancy not currently in remission and/or receiving systemic chemotherapy and/or radiation within 90 days prior to enrollment. Exceptions include chemoembolization for hepatocellular carcinoma or cutaneous malignancies managed with local treatment * Hepatocellular carcinoma with tumor burden outside of the Milan criteria * Serum creatinine \> 2.5 for \> or = six months at the time of enrollment * Personal or family history (first degree relative) 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 30 days prior to liver transplantation, unless patient has documented detectable HCV RNA during this 30 day period * Previous receipt of an HCV protease inhibitor (for subjects enrolling in Part 1: telaprevir) * Receipt of any other investigational study product within 30 days prior to enrollment * Seizure disorder requiring anti-convulsant therapy * Pulmonary arterial hypertension requiring sildenafil or tadalafil infusion (for subjects enrolling in Part 1: telaprevir) * 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 |
|---|---|---|
| Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation | Day 56 | The primary outcome was to determine if MBL-HCV1 in combination with the oral direct-acting antiviral could reduce HCV viral RNA to undetectable at day 56 post transplant and prevent the new liver from becoming productively infected. Undetectable HCV RNA was defined as the level below the lower limit of detection (LLOD) of an FDA-approved polymerase chain reaction (PCR) assay. HCV RNA was quantified by PCR (e.g., COBAS®AmpliPrep/ COBAS® TaqMan® HCV Test manufactured by Roche or equivalent) at each study site |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Day 0 start of first infusion through Day 56 or six weeks after last dose of study treatment whichever is later, up to approximately 126 days | Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Abnormal laboratory values constituted adverse events only if they induced clinical signs or symptoms and/or required therapy that was new or enhanced from baseline. Solicited adverse reactions included the occurrence of the following during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. The presence of any of these symptoms (new or worsening from baseline) was documented as an adverse event. In addition, subjects were asked at all scheduled study visits to report any other adverse events. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 14.1) |
| Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 7, 10, 14, 28, 35, 42, 49, 70, 84, 98, 105, 112 and 126 | The number of subjects with undetectable HCV RNA by study visit day was analyzed utilizing a last value carried forward (LVCF) strategy so that each study visit day had data from (8 subjects in Part 1 and 2 subjects in Part 2), effectively imputing the information for the subjects who had missing data due to a missed study visit, HCV RNA measured with a non-FDA approved assay, or completion of all required post-treatment study visits. The last recorded HCV RNA status for a subject (detectable vs undetectable) was used for the next missing level (in ascending visit number order) until a new HCV RNA level was recorded at a later visit. Serum HCV RNA was measured by Quantitative RT-PCR using an FDA-approved quantitative assay |
| Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Baseline pre-transplant and study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 | Serum HCV RNA was measured by quantitative RT-PCR. The change in log 10 IU/mL HCV viral load from baseline was compared with pre-transplant HCV RNA level and evaluated for each subject at each study visit. Change in the level of HCV RNA in serum, log10(IU/mL), is defined as the difference between the level measured at Baseline and the specified time point. If HCV RNA was not detected by the PCR assay, the lower level of detection of the PCR assay was used for the calculation |
| Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | Pre-transplant, time of viral rebound (assessed from Day 7-Day 56 of treatment), end of study (up to day 126) in subjects who did not achieve a sustained virologic response (SVR) | Conventional sequencing was performed on HCV RNA isolated from a subset of serum samples obtained at baseline, at the time of viral rebound, and at the end of study in subjects who did not achieve a sustained virologic response. The targets of both the MBL-HCV1 antibody (E1/E2 glycoprotein) and telaprevir (NS3) were sequenced. The data displays the number of subjects with \> 20% resistance associated variants (RAV) reported for the target MBL-HCV1 and/or Direct-acting Antiviral (DAA) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 | 12 weeks after the end of treatment (SVR12) and 24 weeks after the end of treatment 12 weeks and 24 weeks post-treatment | Number of subjects with sustained virologic response (defined as HCV RNA concentration below the limit of detection) at 12 and 24 weeks post-treatment was examined as an exploratory endpoint in subjects whose HCV RNA remained undetectable at the 6 week post-treatment safety follow-up visit. Those subjects that had detectable HCV RNA at the end of safety follow-up period were not assessed for SVR 12 and SVR 24. Those subjects achieving an SVR12 were assessed for the durability of the response at 24 weeks after the end of treatment |
Countries
United States
Participant flow
Recruitment details
Chronically infected patients with HCV genotype 1a (Part 1) or genotype 1 (Part 2) scheduled to undergo a liver transplantation were recruited at 5 U.S. transplantation centers between May 2012 and August 2015. Eleven subjects were enrolled. Ten subjects were transplanted and received study intervention in the study (8 in Part 1) and (2 in Part 2).
Pre-assignment details
Reasons for exclusion from study treatment included receipt of an ineligible organ at time of transplant, awaiting transplant at time study enrollment stopped, became ineligible, withdrew consent and subject expired prior to organ offer.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: MBL-HCV1 and Telaprevir MBL-HCV1: 50 mg/kg MBL-HCV1, intravenous, up to 15 infusions over 56 days; option for extended treatment through 84 days if viral load undetectable at day 56
Telaprevir (Part 1): Two 375 mg tablets, 3 times a day up to 56 days; option for extended treatment through 84 days if viral load undetectable at day 56 | 8 |
| Part 2: MBL-HCV1 and Sofosbuvir MBL-HCV1: 50 mg/kg MBL-HCV1, intravenous, up to 15 infusions over 56 days; option for extended treatment through 84 days if viral load undetectable at day 56
Sofosbuvir (Part 2): One 400 mg tablet, 1 time per day up to 56 days; option for extended treatment through 84 days if viral load undetectable at day 56 | 2 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not Transplanted | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: MBL-HCV1 and Telaprevir | Total | Part 2: MBL-HCV1 and Sofosbuvir |
|---|---|---|---|
| Age, Continuous | 59 years | 58 years | 56 years |
| Baseline serum HCV RNA concentration | 5.53 Log10 IU/mL | 5.67 Log10 IU/mL | 6.25 Log10 IU/mL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 10 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hepatocellular Carcinoma | 7 Participants | 8 Participants | 1 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 | 2 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 2 / 2 |
| serious Total, serious adverse events | 7 / 8 | 1 / 2 |
Outcome results
Primary
Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation
The primary outcome was to determine if MBL-HCV1 in combination with the oral direct-acting antiviral could reduce HCV viral RNA to undetectable at day 56 post transplant and prevent the new liver from becoming productively infected. Undetectable HCV RNA was defined as the level below the lower limit of detection (LLOD) of an FDA-approved polymerase chain reaction (PCR) assay. HCV RNA was quantified by PCR (e.g., COBAS®AmpliPrep/ COBAS® TaqMan® HCV Test manufactured by Roche or equivalent) at each study site
Time frame: Day 56
Population: The ten subjects (8 in Part 1 and 2 in Part 2) who initiated study infusions, underwent liver transplantation and received an oral direct-acting antiviral (telaprevir in Part 1 or sofosbuvir in Part 2) were included in the analysis population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation | 4 Participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation | 2 Participants |
Secondary
Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients
Serum HCV RNA was measured by quantitative RT-PCR. The change in log 10 IU/mL HCV viral load from baseline was compared with pre-transplant HCV RNA level and evaluated for each subject at each study visit. Change in the level of HCV RNA in serum, log10(IU/mL), is defined as the difference between the level measured at Baseline and the specified time point. If HCV RNA was not detected by the PCR assay, the lower level of detection of the PCR assay was used for the calculation
Time frame: Baseline pre-transplant and study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98
Population: The ten subjects (8 in Part 1 and 2 in Part 2) who initiated study infusions, underwent liver transplantation and received an oral direct-acting antiviral (telaprevir in Part 1 or sofosbuvir in Part 2) were included in the analysis population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 70 | -2.62 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 7 | -2.97 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 10 | -3.35 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 14 | -3.58 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 28 | -2.94 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 35 | -3.01 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 42 | -2.94 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 49 | -2.89 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 56 | -2.28 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 84 | -2.53 Log10 IU/mL |
| Part 1: MBL-HCV1 and Telaprevir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 98 | -0.76 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 70 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 42 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 7 | -3.46 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 98 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 10 | -3.99 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 49 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 14 | -4.32 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 84 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 28 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 56 | -5.29 Log10 IU/mL |
| Part 2: MBL-HCV1 and Sofosbuvir | Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients | Day 35 | -5.29 Log10 IU/mL |
Secondary
Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment
Conventional sequencing was performed on HCV RNA isolated from a subset of serum samples obtained at baseline, at the time of viral rebound, and at the end of study in subjects who did not achieve a sustained virologic response. The targets of both the MBL-HCV1 antibody (E1/E2 glycoprotein) and telaprevir (NS3) were sequenced. The data displays the number of subjects with \> 20% resistance associated variants (RAV) reported for the target MBL-HCV1 and/or Direct-acting Antiviral (DAA)
Time frame: Pre-transplant, time of viral rebound (assessed from Day 7-Day 56 of treatment), end of study (up to day 126) in subjects who did not achieve a sustained virologic response (SVR)
Population: The ten subjects (8 in Part 1 and 2 in Part 2) who initiated study infusions, underwent liver transplantation and received an oral direct-acting antiviral (telaprevir in Part 1 or sofosbuvir in Part 2) were included in the analysis population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | Pre-transplant | 4 Participants with > 20 % RAV |
| Part 1: MBL-HCV1 and Telaprevir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | Viral Rebound | 4 Participants with > 20 % RAV |
| Part 1: MBL-HCV1 and Telaprevir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | End of Study | 7 Participants with > 20 % RAV |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | Pre-transplant | NA Participants with > 20 % RAV |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | Viral Rebound | NA Participants with > 20 % RAV |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment | End of Study | NA Participants with > 20 % RAV |
Secondary
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126
The number of subjects with undetectable HCV RNA by study visit day was analyzed utilizing a last value carried forward (LVCF) strategy so that each study visit day had data from (8 subjects in Part 1 and 2 subjects in Part 2), effectively imputing the information for the subjects who had missing data due to a missed study visit, HCV RNA measured with a non-FDA approved assay, or completion of all required post-treatment study visits. The last recorded HCV RNA status for a subject (detectable vs undetectable) was used for the next missing level (in ascending visit number order) until a new HCV RNA level was recorded at a later visit. Serum HCV RNA was measured by Quantitative RT-PCR using an FDA-approved quantitative assay
Time frame: Day 7, 10, 14, 28, 35, 42, 49, 70, 84, 98, 105, 112 and 126
Population: The ten subjects (8 in Part 1 and 2 in Part 2) who initiated study infusions, underwent liver transplantation and received an oral direct-acting antiviral (telaprevir in Part 1 or sofosbuvir in Part 2) were included in the analysis population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 14 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 70 | 3 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 35 | 5 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 84 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 10 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 98 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 42 | 5 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 105 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 28 | 4 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 112 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 49 | 5 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 126 | 2 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 7 | 0 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 126 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 7 | 0 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 10 | 0 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 14 | 0 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 28 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 35 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 42 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 49 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 70 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 84 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 98 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 105 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126 | Day 112 | 2 participants |
Secondary
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported
Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Abnormal laboratory values constituted adverse events only if they induced clinical signs or symptoms and/or required therapy that was new or enhanced from baseline. Solicited adverse reactions included the occurrence of the following during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. The presence of any of these symptoms (new or worsening from baseline) was documented as an adverse event. In addition, subjects were asked at all scheduled study visits to report any other adverse events. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 14.1)
Time frame: Day 0 start of first infusion through Day 56 or six weeks after last dose of study treatment whichever is later, up to approximately 126 days
Population: The ten subjects (8 in Part 1 and 2 in Part 2) who initiated study infusions, underwent liver transplantation and received an oral direct-acting antiviral (telaprevir in Part 1 or sofosbuvir in Part 2) were included in the analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Blood And Lymphatic System Disorders | 6 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Cardiac Disorders | 0 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Eye Disorders | 1 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Gastrointestinal Disorders | 9 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | General Disorders And Administration Site Conditions | 12 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Hepatobiliary Disorders | 3 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Immune System Disorders | 2 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Infections And Infestations | 6 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Injury, Poisoning And Procedural Complications | 11 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Investigations | 3 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Metabolism And Nutrition Disorders | 14 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Musculoskeletal And Connective Tissue Disorders | 1 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) | 0 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Nervous System Disorders | 6 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Psychiatric Disorders | 5 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Renal And Urinary Disorders | 1 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Reproductive System And Breast Disorders | 1 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Respiratory, Thoracic And Mediastinal Disorders | 10 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Skin And Subcutaneous Tissue Disorders | 2 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Surgical And Medical Procedures | 0 Events |
| Part 1: MBL-HCV1 and Telaprevir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Vascular Disorders | 5 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Metabolism And Nutrition Disorders | 2 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Blood And Lymphatic System Disorders | 0 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Skin And Subcutaneous Tissue Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Cardiac Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Musculoskeletal And Connective Tissue Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Eye Disorders | 0 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Reproductive System And Breast Disorders | 2 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Gastrointestinal Disorders | 3 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | General Disorders And Administration Site Conditions | 0 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Vascular Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Hepatobiliary Disorders | 0 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Nervous System Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Immune System Disorders | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Respiratory, Thoracic And Mediastinal Disorders | 0 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Infections And Infestations | 2 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Psychiatric Disorders | 2 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Injury, Poisoning And Procedural Complications | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Surgical And Medical Procedures | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Investigations | 1 Events |
| Part 2: MBL-HCV1 and Sofosbuvir | Safety and Tolerability of Study Treatment by Number of Adverse Events Reported | Renal And Urinary Disorders | 0 Events |
Other Pre-specified
Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24
Number of subjects with sustained virologic response (defined as HCV RNA concentration below the limit of detection) at 12 and 24 weeks post-treatment was examined as an exploratory endpoint in subjects whose HCV RNA remained undetectable at the 6 week post-treatment safety follow-up visit. Those subjects that had detectable HCV RNA at the end of safety follow-up period were not assessed for SVR 12 and SVR 24. Those subjects achieving an SVR12 were assessed for the durability of the response at 24 weeks after the end of treatment
Time frame: 12 weeks after the end of treatment (SVR12) and 24 weeks after the end of treatment 12 weeks and 24 weeks post-treatment
Population: Of 8 subjects in Part 1, 2 had undetectable HCV RNA at 6 wk post-treatment. Therefore, at wk 12 (day 168), per protocol, 2 were analyzed. 1 had detectable HCV RNA at wk 12. Per protocol, the subject did not require a 24 wk visit. The other subject had undetectable HCV RNA at wk 12. Therefore, only 1 subject was analyzed at wk 24 (day 252). This subject had undetectable HCV RNA at wk 24.~2 subjects in Part 2 had undetectable HCV RNA at 12 \& 24 wks. 2 subjects were analyzed at the 12 \& 24 wks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 | Post Treatment Week 12 | 1 participants |
| Part 1: MBL-HCV1 and Telaprevir | Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 | Post Treatment Week 24 | 1 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 | Post Treatment Week 12 | 2 participants |
| Part 2: MBL-HCV1 and Sofosbuvir | Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 | Post Treatment Week 24 | 2 participants |