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

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ClinicalTrials.gov Identifier: NCT02455167
Recruitment Status : Active, not recruiting
First Posted : May 27, 2015
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
  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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Simeprivir (SMV) Drug: Sofosbuvir (SOF) Drug: Ribavirin (RBV) Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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)
Study Start Date : May 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


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 Name: Olysio (Simeprivir);

Drug: Sofosbuvir (SOF)
Experimental Single arm study. All participants will get the same treatment.
Other Name: Solvaldi (Sofosbuvir);

Drug: Ribavirin (RBV)
Experimental Single arm study. All participants will get the same treatment.
Other Name: Virazole (Ribavirin);




Primary Outcome Measures :
  1. The sustained virologic response (SVR) in patients infected with HCV genotype 1, cirrhosis, and early clinical decompensation [ Time Frame: 12 weeks ]
  2. Hepatic improvement during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) treatment using a new test of liver function, HepQuant-SHUNT. [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02455167


Locations
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United States, Colorado
University of Colorado Denver (Leprino Building)
Denver, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Amanda Wieland, MD University of Colorado, Denver

Publications of Results:

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02455167     History of Changes
Other Study ID Numbers: 14-0919
UL1TR001082 ( U.S. NIH Grant/Contract )
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:
HCV
Hepatitis C

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents