Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis

August 16, 2021 updated by: University of Colorado, Denver

Reversal of Hepatic Impairment by Achieving Sustained Virologic Response (SVR) With 12 Weeks of Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) in Patients With Hepatitis C Virus (HCV) Genotype 1 Infection and Early Decompensation of Cirrhosis (MELD 10 or Less)

  1. Achieve sustained virologic response (SVR) in patients infected with HCV genotype 1, cirrhosis, and early clinical decompensation using 12 weeks of Olysio/Sovaldi/Ribavirin (or known as: Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin (RBV).
  2. Hepatic improvement during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) treatment using a new test of liver function, HepQuant-SHUNT.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The proposed study will quantify hepatic improvement and antiviral efficacy of the open-label interferon-free combination of 12 weeks of simeprevir (SMV, Simeprevir), sofosbuvir (SOF, Sofosbuvir), and ribavirin (RBV) in patients with HCV genotype 1 infection and early decompensation of cirrhosis. Early decompensation is defined by clinical complications or laboratory deterioration but with a model for end-stage liver disease (MELD) score of 10 or less.

The primary objective of this trial is determination of hepatic functional improvement as measured by the HepQuant (HQ) test during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV). Standard laboratory tests, clinical models (MELD, CTP), liver biopsy, hepatic venous pressure gradient (HVPG), and other imaging tests are insensitive, invasive, or nonspecific.

They may not adequately assess the liver's improvement after viral eradication. In contrast, HepQuant (HQ) tests (Systemic Hepatic Filtration Rate (HFR), Portal HFR, SHUNT,single point cholate concentration (STAT), and DSI) are noninvasive, sensitive, specific, and target an endogenous function, the hepatic uptake of cholate. HQ tests uses serum sampling over a time period of up to 90 minutes to quantify the systemic circulation, portal circulation, and portal-systemic shunt and to derive a disease severity index (DSI) in intact human subjects. The primary endpoint in this treatment trial will be improvement in hepatic function measured by HepQuant (HQ) tests that occurs during and after successful Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV).

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado Denver (Leprino Building)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. HCV genotype 1 infection (all subtypes and Q80K a type of mutation are allowed), and have been approved by a third party payer for the FDA-approved combination of sofosbuvir (SOF) plus ribavirin. The study drug, simeprevir (SMV)
  2. Biopsy proven cirrhosis, or clinical cirrhosis with APRI (AST to Platelet Ratio Index to determine clinical cirrhosis)> 2, Fibrotest > 0.75, or Fibroscan > 12.5 Results Stiffness (kPa).
  3. MELD 10 or less
  4. Expected survival without liver transplantation of >1 year
  5. Patients with Hepatocellular carcinoma (HCC) are included as long as disease MELD is 10 or less, and anticipated time to transplant is >1 year. An example, might be a patient with a subcentimeter HCC who is undergoing serial imaging to document tumor growth to tumor diameter >2 cm prior to listing for transplantation (in order to secure MELD exception). In this case, there could be a time lapse of 3 months or more while monitoring tumor growth, and a further time lapse of 9 months or more until the time of transplantation.
  6. Patients with TIPS or Portal Vein Thrombosis may be included. -

Exclusion Criteria:

  1. Inability to provide informed consent
  2. Known hypersensitivity or serious adverse reaction to any of the study drugs
  3. Age <18 or >80 years
  4. Pregnancy as determined by subject reporting and urine dipstick testing at screening.
  5. Other underlying chronic liver disease - examples that would exclude a patient from participating include but are not limited to nonalcoholic liver disease, alcoholic liver disease, hepatitis B, hemochromatosis, and autoimmune liver disease.
  6. Serious other underlying medical condition - examples include but are not limited to unstable cardiovascular, coronary, or pulmonary disease including right and left sided heart failure, active malignancy other than HCC, or serious infection.
  7. Estimated creatinine clearance < 30 mL min-1 1.73 m2 surface area (BSA)
  8. Hemoglobin <10 g/dL
  9. Neutrophils <500 /μL
  10. Platelets <50,000 /μL
  11. Bilirubin >4 mg/dL
  12. Albumin < 2.8 g/dL
  13. Blood Clotting: International Normalised Ratio (INR) > 2
  14. MELD >10
  15. Child-Turcotte-Pugh class B or C; or, CTP score >7
  16. Conditions that would affect the absorption of orally administered cholate used in the HepQuant® test - such as, extensive intestinal resection, diabetic gastroparesis, and ileal disease or resection.
  17. Concomitant use of both beta-blocker and ACE inhibitor
  18. Subjects taking any other medications with significant drug drug interactions related to the study medications (sofosbuvir, simeprevir, or ribavirin) who cannot discontinue or substitute that medication, will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HCV positive group
A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population.
Drug: Simeprivir (SMV)
Experimental Single arm study. All participants will get the same treatment.
Other Names:
  • Olysio (Simeprivir);
Drug: Sofosbuvir (SOF)
Experimental Single arm study. All participants will get the same treatment.
Other Names:
  • Solvaldi (Sofosbuvir);
Drug: Ribavirin (RBV)
Experimental Single arm study. All participants will get the same treatment.
Other Names:
  • Virazole (Ribavirin);

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation
Time Frame: 12 weeks
Number of participants who cleared Hepatitis C (HCV) after 12 weeks was collected (HCV RNA level was "Not Detected".
12 weeks
Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: Baseline
Time Frame: Baseline
Liver function as assessed via MELD score. The Model For End-Stage Liver Disease (MELD) score assesses the severity of patient liver disease. Possible scores range from 6 to 40, with higher scores indicating more severe liver disease and a worse outcome.
Baseline
Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: 12 Weeks
Time Frame: 12 Weeks
Liver function as assessed via MELD score. The Model For End-Stage Liver Disease (MELD) score assesses the severity of patient liver disease. Possible scores range from 6 to 40, with higher scores indicating more severe liver disease and a worse outcome.
12 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

Janssen Scientific Affairs, LLC

Investigators

  • Principal Investigator: Amanda Wieland, MD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Actual)

July 18, 2016

Study Completion (Actual)

July 18, 2016

Study Registration Dates

First Submitted

April 21, 2015

First Submitted That Met QC Criteria

May 22, 2015

First Posted (Estimate)

May 27, 2015

Study Record Updates

Last Update Posted (Actual)

September 13, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-0919
  • UL1TR001082 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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