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

• Sponsor: MassBiologics (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01532908
• Collaborator: (none)
• Enrollment: 11
• Locations: 5
• Arms: 2
• Actual Duration (Months): 33.1
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Infection	Biological: MBL-HCV1; Drug: Telaprevir (Part 1); Drug: Sofosbuvir (Part 2)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open-Label Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) Combined With Oral Direct-Acting Antivirals in Hepatitis C Infected Patients Undergoing Liver Transplantation
• Actual Study Start Date: Nov 21, 2012
• Actual Primary Completion Date: Aug 27, 2015
• Actual Study Completion Date: Aug 27, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: MBL-HCV1 and Telaprevir	Biological: 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; Drug: 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; Other Names: Incivek (telaprevir)
Experimental: Part 2: MBL-HCV1 and Sofosbuvir	Biological: 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; Drug: 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; Other Names: Sovaldi (sofosbuvir)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

2. 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

3. 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

4. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	Mount Sinai Hospital	New York	New York	United States	10029
5	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas	United States	75203

Sponsors and Collaborators

• MassBiologics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Smith HL, Chung RT, Mantry P, Chapman W, Curry MP, Schiano TD, Boucher E, Cheslock P, Wang Y, Molrine DC. Prevention of allograft HCV recurrence with peri-transplant human monoclonal antibody MBL-HCV1 combined with a single oral direct-acting antiviral: A proof-of-concept study. J Viral Hepat. 2017 Mar;24(3):197-206. doi: 10.1111/jvh.12632. Epub 2016 Nov 7.

• Responsible Party: MassBiologics
• ClinicalTrials.gov Identifier: NCT01532908
• Other Study ID Numbers: MBL-HCV1-11-03
• First Posted: Feb 15, 2012
• Last Update Posted: Feb 5, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by MassBiologics: Liver Transplantation
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Sofosbuvir

Study Results

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 Detail	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.

Arm/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	9	2
Infused	9	2
Transplanted	8	2
COMPLETED	8	2
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir	Total
Arm/Group Description	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	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 of all reporting groups
Overall Participants	8	2	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59	56	58
Sex: Female, Male (Count of Participants)
Female	1 12.5%	0 0%	1 10%
Male	7 87.5%	2 100%	9 90%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	2 100%	10 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 25%	1 50%	3 30%
White	6 75%	1 50%	7 70%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Hepatocellular Carcinoma (Count of Participants)
Count of Participants [Participants]	7 87.5%	1 50%	8 80%
Baseline serum HCV RNA concentration (Log10 IU/mL) [Mean (Full Range) ]
Mean (Full Range) [Log10 IU/mL]	5.53	6.25	5.67

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	8	2
Count of Participants [Participants]	4 50%	2 100%

2. Secondary Outcome

Title	Safety and Tolerability of Study Treatment by Number of Adverse Events Reported
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	8	2
Blood And Lymphatic System Disorders	6	0
Cardiac Disorders	0	1
Eye Disorders	1	0
Gastrointestinal Disorders	9	3
General Disorders And Administration Site Conditions	12	0
Hepatobiliary Disorders	3	0
Immune System Disorders	2	1
Infections And Infestations	6	2
Injury, Poisoning And Procedural Complications	11	1
Investigations	3	1
Metabolism And Nutrition Disorders	14	2
Musculoskeletal And Connective Tissue Disorders	1	1
Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)	0	1
Nervous System Disorders	6	1
Psychiatric Disorders	5	2
Renal And Urinary Disorders	1	0
Reproductive System And Breast Disorders	1	2
Respiratory, Thoracic And Mediastinal Disorders	10	0
Skin And Subcutaneous Tissue Disorders	2	1
Surgical And Medical Procedures	0	1
Vascular Disorders	5	1

3. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	8	2
Day 7	0 0%	0 0%
Day 10	2 25%	0 0%
Day 14	2 25%	0 0%
Day 28	4 50%	2 100%
Day 35	5 62.5%	2 100%
Day 42	5 62.5%	2 100%
Day 49	5 62.5%	2 100%
Day 70	3 37.5%	2 100%
Day 84	2 25%	2 100%
Day 98	2 25%	2 100%
Day 105	2 25%	2 100%
Day 112	2 25%	2 100%
Day 126	2 25%	2 100%

4. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	8	2
Day 7	-2.97	-3.46
Day 10	-3.35	-3.99
Day 14	-3.58	-4.32
Day 28	-2.94	-5.29
Day 35	-3.01	-5.29
Day 42	-2.94	-5.29
Day 49	-2.89	-5.29
Day 56	-2.28	-5.29
Day 70	-2.62	-5.29
Day 84	-2.53	-5.29
Day 98	-0.76	-5.29

5. Secondary Outcome

Title	Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	8	2
Pre-transplant	4 50%	NA NaN
Viral Rebound	4 50%	NA NaN
End of Study	7 87.5%	NA NaN

6. Other Pre-specified Outcome

Title	Number of Subjects With Sustained Virologic Response (SVR) at Week 12 and Week 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: MBL-HCV1 and Telaprevir	Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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	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
Measure Participants	2	2
Post Treatment Week 12	1 12.5%	2 100%
Post Treatment Week 24	1 12.5%	2 100%

Adverse Events

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
Adverse Event Reporting Description	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)
Arm/Group Title	Part 1: MBL-HCV1 and Telaprevir		Part 2: MBL-HCV1 and Sofosbuvir
Arm/Group Description	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		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
All Cause Mortality
	Part 1: MBL-HCV1 and Telaprevir		Part 2: MBL-HCV1 and Sofosbuvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1: MBL-HCV1 and Telaprevir		Part 2: MBL-HCV1 and Sofosbuvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)		1/2 (50%)
General disorders
GENERALISED OEDEMA	1/8 (12.5%)	1	0/2 (0%)	0
OEDEMA PERIPHERAL	1/8 (12.5%)	1	0/2 (0%)	0
Hepatobiliary disorders
CHOLANGITIS	1/8 (12.5%)	1	0/2 (0%)	0
Immune system disorders
LIVER TRANSPLANT REJECTION	0/8 (0%)	0	1/2 (50%)	1
TRANSPLANT REJECTION	2/8 (25%)	2	0/2 (0%)	0
Infections and infestations
CELLULITIS	2/8 (25%)	2	0/2 (0%)	0
HERPES ZOSTER	0/8 (0%)	0	1/2 (50%)	1
Injury, poisoning and procedural complications
POST PROCEDURAL HAEMORRHAGE	1/8 (12.5%)	1	0/2 (0%)	0
Metabolism and nutrition disorders
HYPERKALAEMIA	3/8 (37.5%)	3	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Part 1: MBL-HCV1 and Telaprevir		Part 2: MBL-HCV1 and Sofosbuvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		2/2 (100%)
Blood and lymphatic system disorders
ANAEMIA	3/8 (37.5%)	3	0/2 (0%)	0
LEUKOCYTOSIS	2/8 (25%)	2	0/2 (0%)	0
THROMBOCYTOPENIA	1/8 (12.5%)	1	0/2 (0%)	0
Cardiac disorders
PALPITATIONS	0/8 (0%)	0	1/2 (50%)	1
Eye disorders
VISION BLURRED	1/8 (12.5%)	1	0/2 (0%)	0
Gastrointestinal disorders
ABDOMINAL DISTENSION	2/8 (25%)	2	0/2 (0%)	0
ABDOMINAL PAIN	1/8 (12.5%)	1	0/2 (0%)	0
ABDOMINAL PAIN UPPER	0/8 (0%)	0	1/2 (50%)	1
CONSTIPATION	1/8 (12.5%)	1	1/2 (50%)	1
DIARRHOEA	1/8 (12.5%)	1	1/2 (50%)	1
DYSPEPSIA	1/8 (12.5%)	1	0/2 (0%)	0
GLOSSODYNIA	1/8 (12.5%)	1	0/2 (0%)	0
NAUSEA	2/8 (25%)	2	0/2 (0%)	0
OEDEMA	1/8 (12.5%)	1	0/2 (0%)	0
General disorders
CHEST PAIN	1/8 (12.5%)	1	0/2 (0%)	0
FATIGUE	2/8 (25%)	2	0/2 (0%)	0
OEDEMA PERIPHERAL	3/8 (37.5%)	4	0/2 (0%)	0
PYREXIA	2/8 (25%)	2	0/2 (0%)	0
Hepatobiliary disorders
BILE DUCT STENOSIS	1/8 (12.5%)	1	0/2 (0%)	0
JAUNDICE	1/8 (12.5%)	1	0/2 (0%)	0
Infections and infestations
CANDIDIASIS	1/8 (12.5%)	1	0/2 (0%)	0
CELLULITIS	0/8 (0%)	0	1/2 (50%)	1
CYTOMEGALOVIRUS INFECTION	1/8 (12.5%)	1	0/2 (0%)	0
LUNG INFECTION PSEUDOMONAL	1/8 (12.5%)	1	0/2 (0%)	0
ORAL CANDIDIASIS	1/8 (12.5%)	1	0/2 (0%)	0
Injury, poisoning and procedural complications
INCISION SITE COMPLICATION	1/8 (12.5%)	1	0/2 (0%)	0
INCISION SITE ERYTHEMA	1/8 (12.5%)	1	0/2 (0%)	0
INCISION SITE PAIN	4/8 (50%)	4	0/2 (0%)	0
INCISION SITE PRURITUS	1/8 (12.5%)	1	0/2 (0%)	0
INCISIONAL HERNIA	0/8 (0%)	0	1/2 (50%)	1
OPERATIVE HAEMORRHAGE	1/8 (12.5%)	1	0/2 (0%)	0
TOXICITY TO VARIOUS AGENTS	1/8 (12.5%)	1	0/2 (0%)	0
WOUND DEHISCENCE	1/8 (12.5%)	1	0/2 (0%)	0
Investigations
BLOOD BILIRUBIN INCREASED	1/8 (12.5%)	1	0/2 (0%)	0
BLOOD CREATININE INCREASED	2/8 (25%)	2	0/2 (0%)	0
LIVER FUNCTION TEST ABNORMAL	0/8 (0%)	0	1/2 (50%)	1
Metabolism and nutrition disorders
DECREASED APPETITE	2/8 (25%)	2	0/2 (0%)	0
DIABETES MELLITUS	1/8 (12.5%)	1	1/2 (50%)	1
ELECTROLYTE IMBALANCE	1/8 (12.5%)	1	0/2 (0%)	0
HYPERGLYCAEMIA	2/8 (25%)	2	0/2 (0%)	0
HYPERKALAEMIA	2/8 (25%)	3	0/2 (0%)	0
HYPOALBUMINAEMIA	2/8 (25%)	2	0/2 (0%)	0
HYPOMAGNESAEMIA	0/8 (0%)	0	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/8 (12.5%)	1	0/2 (0%)	0
PAIN IN EXTREMITY	0/8 (0%)	0	1/2 (50%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SKIN PAPILLOMA	0/8 (0%)	0	1/2 (50%)	1
Nervous system disorders
DIZZINESS	1/8 (12.5%)	1	0/2 (0%)	0
HEADACHE	2/8 (25%)	3	0/2 (0%)	0
TREMOR	1/8 (12.5%)	1	1/2 (50%)	1
VOCAL CORD PARALYSIS	1/8 (12.5%)	1	0/2 (0%)	0
Psychiatric disorders
AGITATION	1/8 (12.5%)	1	0/2 (0%)	0
ANXIETY	2/8 (25%)	3	0/2 (0%)	0
DELIRIUM	0/8 (0%)	0	1/2 (50%)	1
DEPRESSION	0/8 (0%)	0	1/2 (50%)	1
INSOMNIA	1/8 (12.5%)	1	0/2 (0%)	0
Renal and urinary disorders
RENAL FAILURE ACUTE	1/8 (12.5%)	1	0/2 (0%)	0
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	1/8 (12.5%)	1	0/2 (0%)	0
ERECTILE DYSFUNCTION	0/8 (0%)	0	1/2 (50%)	1
TESTICULAR SWELLING	0/8 (0%)	0	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	4/8 (50%)	5	0/2 (0%)	0
DYSPNOEA EXERTIONAL	1/8 (12.5%)	1	0/2 (0%)	0
PLEURAL EFFUSION	1/8 (12.5%)	1	0/2 (0%)	0
PULMONARY OEDEMA	1/8 (12.5%)	1	0/2 (0%)	0
RESPIRATORY DISTRESS	1/8 (12.5%)	1	0/2 (0%)	0
WHEEZING	1/8 (12.5%)	1	0/2 (0%)	0
Skin and subcutaneous tissue disorders
HYPERHIDROSIS	1/8 (12.5%)	1	0/2 (0%)	0
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	0/8 (0%)	0	1/2 (50%)	1
RASH PAPULAR	1/8 (12.5%)	1	0/2 (0%)	0
Surgical and medical procedures
HERNIA REPAIR	0/8 (0%)	0	1/2 (50%)	1
Vascular disorders
HYPERTENSION	3/8 (37.5%)	3	1/2 (50%)	1
HYPOTENSION	1/8 (12.5%)	1	0/2 (0%)	0
REPERFUSION INJURY	1/8 (12.5%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.