Trial Outcomes & Findings for Open Label Study of the Efficacy and Safety of MBL-HCV1 in Combination With Oral Direct-Acting Antivirals in Patients Undergoing Liver Transplantation for Hepatitis C (NCT NCT01532908)

Last Updated: 2021-02-05

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Day 56

Results posted on

2021-02-05

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	9	2
Overall Study Infused	9	2
Overall Study Transplanted	8	2
Overall Study COMPLETED	8	2
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Overall Study Not Transplanted	1	0

Baseline Characteristics

Open Label Study of the Efficacy and Safety of MBL-HCV1 in Combination With Oral Direct-Acting Antivirals in Patients Undergoing Liver Transplantation for Hepatitis C

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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	Total n=10 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	56 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Hepatocellular Carcinoma	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Baseline serum HCV RNA concentration	5.53 Log10 IU/mL n=5 Participants	6.25 Log10 IU/mL n=7 Participants	5.67 Log10 IU/mL n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation	4 Participants	2 Participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Blood And Lymphatic System Disorders	6 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Cardiac Disorders	0 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Eye Disorders	1 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Gastrointestinal Disorders	9 Events	3 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported General Disorders And Administration Site Conditions	12 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Hepatobiliary Disorders	3 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Immune System Disorders	2 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Infections And Infestations	6 Events	2 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Injury, Poisoning And Procedural Complications	11 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Investigations	3 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Metabolism And Nutrition Disorders	14 Events	2 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Musculoskeletal And Connective Tissue Disorders	1 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)	0 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Nervous System Disorders	6 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Psychiatric Disorders	5 Events	2 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Renal And Urinary Disorders	1 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Reproductive System And Breast Disorders	1 Events	2 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Respiratory, Thoracic And Mediastinal Disorders	10 Events	0 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Skin And Subcutaneous Tissue Disorders	2 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Surgical And Medical Procedures	0 Events	1 Events
Safety and Tolerability of Study Treatment by Number of Adverse Events Reported Vascular Disorders	5 Events	1 Events

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
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	0 participants
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	0 participants
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	0 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants
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	2 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
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 Interval -5.54 to 1.39	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -3.94 to -2.45	-3.46 Log10 IU/mL Interval -3.57 to -3.35
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 Interval -4.32 to -2.2	-3.99 Log10 IU/mL Interval -4.38 to -3.6
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 Interval -4.7 to -1.87	-4.32 Log10 IU/mL Interval -4.85 to -3.8
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 Interval -5.54 to 1.57	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -5.54 to 1.69	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -5.54 to 1.8	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -5.54 to 1.78	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -5.54 to 1.86	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -5.16 to 1.41	-5.29 Log10 IU/mL Interval -5.38 to -5.19
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 Interval -4.62 to 1.48	-5.29 Log10 IU/mL Interval -5.38 to -5.19

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
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	NA Participants with > 20 % RAV 1 For the Part 2: MBL-HCV1 and Sofosbuvir" Arm/Group Pre-transplant timepoint, virus was available but not analyzed because there was no viral rebound, therefore there was no virus available for comparison.
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	NA Participants with > 20 % RAV 2 For the Part 2: MBL-HCV1 and Sofosbuvir" Arm/Group both subjects had undetectable HCV RNA by day 21 and remained undetectable for 24 weeks post-treatment (SVR24), therefore there was no virus available for analysis.
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	NA Participants with > 20 % RAV 2 For the Part 2: MBL-HCV1 and Sofosbuvir" Arm/Group both subjects had undetectable HCV RNA by day 21 and remained undetectable for 24 weeks post-treatment (SVR24), therefore there was no virus available for analysis.

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Part 1: MBL-HCV1 and Telaprevir n=2 Participants 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 Participants 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
Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 Post Treatment Week 12	1 participants	2 participants
Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24 Post Treatment Week 24	1 participants	2 participants

Adverse Events

Part 1: MBL-HCV1 and Telaprevir

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 2: MBL-HCV1 and Sofosbuvir

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: MBL-HCV1 and Telaprevir n=8 participants at risk 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	Part 2: MBL-HCV1 and Sofosbuvir n=2 participants at risk 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
General disorders GENERALISED OEDEMA	12.5% 1/8 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
General disorders OEDEMA PERIPHERAL	12.5% 1/8 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Hepatobiliary disorders CHOLANGITIS	12.5% 1/8 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Immune system disorders LIVER TRANSPLANT REJECTION	0.00% 0/8 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	50.0% 1/2 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Immune system disorders TRANSPLANT REJECTION	25.0% 2/8 • Number of events 2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Infections and infestations CELLULITIS	25.0% 2/8 • Number of events 2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Infections and infestations HERPES ZOSTER	0.00% 0/8 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	50.0% 1/2 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	12.5% 1/8 • Number of events 1 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)
Metabolism and nutrition disorders HYPERKALAEMIA	37.5% 3/8 • Number of events 3 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)	0.00% 0/2 • 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. The following adverse reactions were solicited during or immediately after the infusion: arthralgia, chills, dyspnea, fatigue, fever, headache, nausea, hives, or rash. Summarized by System Organ Class (SOC) and Preferred Term (PT)

Other adverse events

Additional Information

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