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

NCT01532908 | Terminated Phase 2 Results

• 1 other identifier: MBL-HCV1-11-03
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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.

Conditions

Hepatitis C Infection

Keywords

Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• 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

  Day 56

Secondary Outcomes (4)

• 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

• 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

• 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

• 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)

Other Outcomes (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

Study Arms (2)

Part 1: MBL-HCV1 and Telaprevir

EXPERIMENTAL

Biological: MBL-HCV1; Drug: Telaprevir (Part 1)

Part 2: MBL-HCV1 and Sofosbuvir

EXPERIMENTAL

Biological: MBL-HCV1; Drug: Sofosbuvir (Part 2)

Interventions

MBL-HCV1 BIOLOGICAL

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

Part 1: MBL-HCV1 and Telaprevir; Part 2: MBL-HCV1 and Sofosbuvir

Telaprevir (Part 1) DRUG

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

Also known as: Incivek (telaprevir)

Part 1: MBL-HCV1 and Telaprevir

Sofosbuvir (Part 2) DRUG

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

Also known as: Sovaldi (sofosbuvir)

Part 2: MBL-HCV1 and Sofosbuvir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• MassBiologics: lead

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Related Publications (1)

• 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.

  PMID: 28127942 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

telaprevir; Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Director of Clinical Affairs
• Organization: MassBiologics

Mblclinicaldirector@Umassmed.edu

617-474-3000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 15, 2012
• Study Start: November 21, 2012
• Primary Completion: August 27, 2015
• Study Completion: August 27, 2015
• Last Updated: February 5, 2021
• Results First Posted: February 5, 2021

Record last verified: 2021-02

Locations

US (5)