HCV InfectionPhase 2MBL-HCV1NCT01121185
Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C
A Phase 2 study testing MBL-HCV1 in people with HCV Infection and Liver Transplantation, run by MassBiologics at 8 sites in United States.
Trial summary
The purpose of this study is to determine whether a human monoclonal antibody against Hepatitis C (MBL-HCV1) is effective in preventing detectable levels of Hepatitis C virus in patients undergoing liver transplantation due to chronic HCV infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCV Infection, Liver Transplantation
- What is being tested?
- MBL-HCV1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 8 sitesUnited States
- Study dates
- Jun 2010to Jun 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient ≥ 18 years of age with documented chronic hepatitis C virus infection of genotype 1a undergoing liver transplantation from either a deceased donor or living donor.
- Patient or legal guardian/health care proxy must have read, understood and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained.
Who cannot join
- Positive serology for Hepatitis B surface Antigen
- Positive serology for HIV
- Pregnancy or breastfeeding
- Previous history of any organ transplant
- Planned receipt of combined organ transplant (e.g. liver and kidney)
- Receipt or planned receipt of immune globulin (IVIG) within 90 days of enrollment
Show all 15Show fewer
- History of extrahepatic malignancy and/or receiving chemotherapy within 90 days prior to enrollment with the exception of chemoembolization for hepatocellular carcinoma
- Hepatocellular carcinoma with tumor burden outside of the Milan criteria
- History of chronic renal insufficiency or creatinine > 2.5 for ≥ six months
- Personal or family history of deep venous thrombosis or pulmonary embolism
- Receipt of liver allograft from HCV positive donor or Hepatitis B core antibody positive donor
- Receipt of liver allograft donated after cardiac death of donor
- Receipt of any antiviral agents, licensed or investigational for hepatitis C virus within 90 days prior to enrollment
- Receipt of any other investigational study product within 30 days prior to enrollment
- Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely that the patient could complete the study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Lahey Clinic
Burlington, Massachusetts, 01805
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Health System
Detroit, Michigan, 48202
Methodist Healthcare Foundation
Memphis, Tennessee, 38104
Yale-New Haven Hospital
New Haven, Connecticut, 06504
Mount Sinai Hospital
New York, New York, 10029
About this study
Official title: A Phase II Randomized, Double-Blind, Placebo Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) in Hepatitis C Infected Patients Undergoing Liver Transplantation
The purpose of this study is to determine whether a human monoclonal antibody against Hepatitis C (MBL-HCV1) is effective in preventing detectable levels of Hepatitis C virus in patients undergoing liver transplantation due to chronic HCV infection. The study will also determine if MBL-HCV1 is effective in delaying or reducing the amount of detectable HCV in patients after transplant.
Read the detailed description
This is a Phase 2, randomized, double-blind, placebo controlled study in Hepatitis C (HCV) infected patients undergoing liver transplantation. Chronically infected patients with HCV genotype 1a scheduled to receive a liver transplant from either a deceased or living donor who satisfy all study inclusion or exclusion criteria will be approached to participate. The study will be conducted in two parts to test a human monoclonal antibody against Hepatitis C (MBL-HCV1). In Part 1, sixteen eligible patients will be randomized 1:1 to receive 50 mg/kg MBL-HCV1 or 0.9% sodium chloride placebo intravenously. Eleven doses will be given during the first 14 days post transplantation. Patients will be evaluated through day 56 for safety and clinical outcomes that include measurement of anti-HCV antibodies, anti-drug antibody and HCV viral load. On study visit day 42, a liver biopsy will be performed for evaluation of hepatitis. Physical examination, vital sign measurements, emergence of adverse events and concomitant medication usage will be assessed at scheduled visits and as needed during the 56 day study period.
The Data Safety and Monitoring Board will perform a futility analysis after the first 16 patients have been enrolled and completed study follow-up through study visit day 42 post transplant. Based on the results of the interim analysis, the dose of MBL-HCV1 for part 2 of the study will be determined. Part 2 of the study will be conducted in the same manner as Part 1.
- Conditions
- HCV Infection, Liver Transplantation
- Being tested
- MBL-HCV1, 0.9% Sodium chloride Placebo
- Keywords
- Hepatitis C virus (HCV), Liver transplantation, Human Monoclonal Antibody
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MBL-HCV1Biological
50 mg/kg MBL-HCV1, intravenous
0.9% Sodium chloride PlaceboOther
Also called Normal Saline
0.9% sodium chloride, intravenous
| Study group | Role | What they receive |
|---|---|---|
| MBL-HCV1 | Experimental | Not described Receives: Biological: MBL-HCV1 |
| 0.9% sodium chloride | Placebo comparator | Not described Receives: Other: 0.9% Sodium chloride Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Measured: At Day 42 post-transplantation
Secondary outcomes (7)
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation
Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Subjects were asked at scheduled study visits through day 42 whether they experienced solicited adverse reactions (fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives). In addition to these solicited adverse events, subjects were asked at all scheduled study visits through day 56 to report any other adverse events, regardless of whether the event was thought to be related to the study infusions. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 12.0)
Measured: Through Day 56
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Serum HCV RNA was measured by quantitative RT-PCR. The change in HCV RNA from baseline was obtained by calculating the difference between the baseline pre-transplantation HCV RNA level and the HCV RNA level measured at each study visit.
Measured: Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42
Liver biopsies obtained at baseline (day 0) and day 42 post-transplantation were assessed for histologic evidence of hepatitis by a pathologist blinded to treatment assignment using the Ishak modification of the Knodell histologic grading system to assign a histologic activity index (HAI) score. The HAI score consists of a sum of four components: 1) periportal or periseptal interface hepatitis; 2) confluent necrosis; 3) focal lytic necrosis, apoptosis and focal inflammation; 4) portal inflammation. The total HAI score can range from a minimum of 0 to a maximum of 18, with higher scores indicating more severe hepatic inflammation.
Measured: Baseline Day 0 and Day 42
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR)
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the INR at each time-point. The INR is the ratio of a patient's prothrombin time to a control sample, raised to the power of the ISI value (International Sensitivity Index) for the batch of tissue factor being used for the assay.
Measured: Through Day 56
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT)
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the ALT at each time-point.
Measured: Through Day 56
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin
Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the total bilirubin at each time-point.
Measured: Through Day 56
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
Measured: Through Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2010 (estimated)
- Study startJun 2010
- Primary completionJun 2011
- Study completionJun 2011
Why it stopped: The study was terminated due to slower than anticipated subject accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HCV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- MassBiologics
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Deborah C. Molrine, MD, Study director, Massbiologics of University of Massachusetts Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01121185
- Sponsor's protocol ID
- MBL-HCV1-10-02
- Acronym
- MBL-HCV1
- Status last verified
- Mar 2016
- First submitted
- 6 May 2010
- Last updated
- 14 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chung RT, Gordon FD, Curry MP, Schiano TD, Emre S, Corey K, Markmann JF, Hertl M, Pomposelli JJ, Pomfret EA, Florman S, Schilsky M, Broering TJ, Finberg RW, Szabo G, Zamore PD, Khettry U, Babcock GJ, Ambrosino DM, Leav B, Leney M, Smith HL, Molrine DC. Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study. Am J Transplant. 2013 Apr;13(4):1047-1054. doi: 10.1111/ajt.12083. Epub 2013 Jan 28.
PubMed 23356386
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-Blind, Placebo Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) in Hepatitis C Infected Patients Undergoing Liver Transplantation
- ClinicalTrials.gov ID
- NCT01121185
- Acronym / sponsor ID
- MBL-HCV1 / MBL-HCV1-10-02
- Conditions
- HCV Infection, Liver Transplantation
- Keywords
- Hepatitis C virus (HCV), Liver transplantation, Human Monoclonal Antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to slower than anticipated subject accrual.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- MassBiologicsUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 12 May 2010 (estimated)
- Results
- Posted 14 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether a human monoclonal antibody against Hepatitis C (MBL-HCV1) is effective in preventing detectable levels of Hepatitis C virus in patients undergoing liver transplantation due to chronic HCV infection. The study will also determine if MBL-HCV1 is effective in delaying or reducing the amount of detectable HCV in patients after transplant.
Detailed description
This is a Phase 2, randomized, double-blind, placebo controlled study in Hepatitis C (HCV) infected patients undergoing liver transplantation. Chronically infected patients with HCV genotype 1a scheduled to receive a liver transplant from either a deceased or living donor who satisfy all study inclusion or exclusion criteria will be approached to participate. The study will be conducted in two parts to test a human monoclonal antibody against Hepatitis C (MBL-HCV1). In Part 1, sixteen eligible patients will be randomized 1:1 to receive 50 mg/kg MBL-HCV1 or 0.9% sodium chloride placebo intravenously. Eleven doses will be given during the first 14 days post transplantation. Patients will be evaluated through day 56 for safety and clinical outcomes that include measurement of anti-HCV antibodies, anti-drug antibody and HCV viral load. On study visit day 42, a liver biopsy will be performed for evaluation of hepatitis. Physical examination, vital sign measurements, emergence of adverse events and concomitant medication usage will be assessed at scheduled visits and as needed during the 56 day study period.
The Data Safety and Monitoring Board will perform a futility analysis after the first 16 patients have been enrolled and completed study follow-up through study visit day 42 post transplant. Based on the results of the interim analysis, the dose of MBL-HCV1 for part 2 of the study will be determined. Part 2 of the study will be conducted in the same manner as Part 1.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MBL-HCV1 | Experimental | Biological: MBL-HCV1 |
| 0.9% sodium chloride | Placebo comparator | Other: 0.9% Sodium chloride Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient ≥ 18 years of age with documented chronic hepatitis C virus infection of genotype 1a undergoing liver transplantation from either a deceased donor or living donor.
- Patient or legal guardian/health care proxy must have read, understood and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained.
Key exclusion criteria (15 listed)
- Positive serology for Hepatitis B surface Antigen
- Positive serology for HIV
- Pregnancy or breastfeeding
- Previous history of any organ transplant
- Planned receipt of combined organ transplant (e.g. liver and kidney)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MBL-HCV150 mg/kg MBL-HCV1, intravenous | Biological | MBL-HCV1 |
| 0.9% Sodium chloride PlaceboAlso: Normal Saline0.9% sodium chloride, intravenous | Other | 0.9% sodium chloride |
Primary outcome
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
Time frame: At Day 42 post-transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
7 secondary outcomes
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation
Time frame: Through Day 56
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Time frame: Baseline and Day 3, 14, 28 and 42 Post-Transplantation
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42
Time frame: Baseline Day 0 and Day 42
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR)
Time frame: Through Day 56
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT)
Time frame: Through Day 56
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin
Time frame: Through Day 56
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation
Time frame: Through Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23356386Chung RT, Gordon FD, Curry MP, Schiano TD, Emre S, Corey K, Markmann JF, Hertl M, Pomposelli JJ, Pomfret EA, Florman S, Schilsky M, Broering TJ, Finberg RW, Szabo G, Zamore PD, Khettry U, Babcock GJ, Ambrosino DM, Leav B, Leney M, Smith HL, Molrine DC. Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study. Am J Transplant. 2013 Apr;13(4):1047-1054. doi: 10.1111/ajt.12083. Epub 2013 Jan 28.
Related trials for HCV Infection
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Recruiting
HIV/HBV/HCV Triple Screening in Primary Care
HIV, HBV (Hepatitis B Virus)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah C. Molrine, MD study director
Massbiologics of University of Massachusetts Medical School
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MBL-HCV1 in people with HCV Infection and Liver Transplantation, run by MassBiologics at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation (time frame: At Day 42 post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01121185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2016.