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Hepatitis CPhase 3NCT02455167

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

A Phase 3 study testing Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in people with Hepatitis C, run by University of Colorado, Denver at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Hepatitis C
What is being tested?
Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
May 2015to 18 Jul 2016
Phase
Phase 3
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • 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).
  • MELD 10 or less
  • Expected survival without liver transplantation of >1 year
  • 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.
  • Patients with TIPS or Portal Vein Thrombosis may be included. -

Who cannot join

  • Inability to provide informed consent
  • Known hypersensitivity or serious adverse reaction to any of the study drugs
  • Age <18 or >80 years
  • Pregnancy as determined by subject reporting and urine dipstick testing at screening.
  • 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.
  • 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.
Show all 18Show fewer
  • Estimated creatinine clearance < 30 mL min-1 1.73 m2 surface area (BSA)
  • Hemoglobin <10 g/dL
  • Neutrophils <500 /μL
  • Platelets <50,000 /μL
  • Bilirubin >4 mg/dL
  • Albumin < 2.8 g/dL
  • Blood Clotting: International Normalised Ratio (INR) > 2
  • MELD >10
  • Child-Turcotte-Pugh class B or C; or, CTP score >7
  • 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.
  • Concomitant use of both beta-blocker and ACE inhibitor
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Colorado Denver (Leprino Building)

    Denver, Colorado, 80045

Other trials in United States

About this study

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)

  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.
Read the 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).

Conditions
Hepatitis C
Being tested
Simeprivir (SMV), Sofosbuvir (SOF), Ribavirin (RBV)
Keywords
HCV, Hepatitis C
Medical subject headings
Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Simeprivir (SMV)Drug

    Also called Olysio (Simeprivir);

    Experimental Single arm study. All participants will get the same treatment.

  • Sofosbuvir (SOF)Drug

    Also called Solvaldi (Sofosbuvir);

    Experimental Single arm study. All participants will get the same treatment.

  • Ribavirin (RBV)Drug

    Also called Virazole (Ribavirin);

    Experimental Single arm study. All participants will get the same treatment.

Study groups in NCT02455167
Study groupRoleWhat they receive
HCV positive groupExperimentalA single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population.
Receives: Drug: Simeprivir (SMV); Drug: Sofosbuvir (SOF); Drug: Ribavirin (RBV)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation

    Number of participants who cleared Hepatitis C (HCV) after 12 weeks was collected (HCV RNA level was "Not Detected".

    Measured: 12 weeks

  2. Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: 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.

    Measured: Baseline

  3. Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: 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.

    Measured: 12 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2015 (estimated)
  2. Study startMay 2015
  3. Primary completion18 Jul 2016
  4. Study completion18 Jul 2016

Why it stopped: Study stopped due to low accrual and availability of other treatment options

Resources

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 3
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02455167
Sponsor's protocol ID
14-0919
Other IDs
UL1TR001082
Status last verified
Aug 2021
First submitted
21 Apr 2015
Last updated
13 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Everson GT, Martucci MA, Shiffman ML, Sterling RK, Morgan TR, Hoefs JC; HALT-C trial group. Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt. Aliment Pharmacol Ther. 2007 Aug 1;26(3):401-10. doi: 10.1111/j.1365-2036.2007.03389.x.

    PubMed 17635375
  • Everson GT, Shiffman ML, Morgan TR, Hoefs JC, Sterling RK, Wagner DA, Kulig CC, Curto TM, Wright EC; Halt-C Trial Group. The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis Trial. Aliment Pharmacol Ther. 2008 May;27(9):798-809. doi: 10.1111/j.1365-2036.2008.03639.x. Epub 2008 Feb 7.

    PubMed 18266997
  • Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Desanto JL, Curto TM, Wright EC; HALT-C Trial Group. Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial. Aliment Pharmacol Ther. 2009 Mar 1;29(5):589-601. doi: 10.1111/j.1365-2036.2008.03908.x. Epub 2008 Dec 1.

    PubMed 19053983
  • Everson GT. Hepatic cysts in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1993 Oct;22(4):520-5. doi: 10.1016/s0272-6386(12)80923-1. No abstract available.

    PubMed 8213790
  • Shrestha R, McKinley C, Showalter R, Wilner K, Marsano L, Vivian B, Everson GT. Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis. Liver Transpl Surg. 1997 Mar;3(2):166-73. doi: 10.1002/lt.500030210.

    PubMed 9346731
  • Shaheen AA, Wan AF, Myers RP. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. Am J Gastroenterol. 2007 Nov;102(11):2589-600. doi: 10.1111/j.1572-0241.2007.01466.x. Epub 2007 Sep 10.

    PubMed 17850410
  • Tripodi A, Caldwell SH, Hoffman M, Trotter JF, Sanyal AJ. Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease. Aliment Pharmacol Ther. 2007 Jul 15;26(2):141-8. doi: 10.1111/j.1365-2036.2007.03369.x.

    PubMed 17593061

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in people with Hepatitis C, run by University of Colorado, Denver at 1 site 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 6 inclusion and 18 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 13 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 13 Sep 2021). 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?

The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation (time frame: 12 weeks). The study lists 3 primary outcomes in all. 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 NCT02455167, which also lists 7 linked publications.

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 13 Sep 2021.

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