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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02455167
• Collaborator: Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 14.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• 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 1, 2015
• Actual Primary Completion Date: Jul 18, 2016
• Actual Study Completion Date: Jul 18, 2016

Arms and Interventions

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);

Outcome Measures

Primary Outcome Measures

1. The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation [12 weeks]

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

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

3. Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: 12 Weeks [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver (Leprino Building)	Denver	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• Janssen Scientific Affairs, LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02455167
• Other Study ID Numbers: 14-0919; UL1TR001082
• First Posted: May 27, 2015
• Last Update Posted: Sep 13, 2021
• Last Verified: Aug 1, 2021

• 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: Hepatitis A; Hepatitis C; Hepatitis; Ribavirin; Sofosbuvir

Study Results

Participant Flow

Pre-assignment Detail	5 participants screen-failed after enrollment.

Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	3 75%
Male	1 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 50%
Not Hispanic or Latino	2 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 25%
White	3 75%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation
Description	Number of participants who cleared Hepatitis C (HCV) after 12 weeks was collected (HCV RNA level was "Not Detected".
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
Measure Participants	4
Count of Participants [Participants]	4 100%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
Measure Participants	4
Mean (Full Range) [score on a scale]	8

3. Primary Outcome

Title	Hepatic Improvement During and After Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) Treatment Using a New Test of Liver Function, HepQuant-SHUNT: 12 Weeks
Description	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.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
Measure Participants	4
Mean (Full Range) [score on a scale]	7.25

Adverse Events

Time Frame	12 Weeks
Arm/Group Title	HCV Positive Group
Arm/Group Description	A single arm study of 'Simeprivir (SMV), Sofosbuvir (SOF) and Ribavirin (RBV) in an HCV positive population. Simeprivir (SMV): Experimental Single arm study. All participants will get the same treatment. Sofosbuvir (SOF): Experimental Single arm study. All participants will get the same treatment. Ribavirin (RBV): Experimental Single arm study. All participants will get the same treatment.
All Cause Mortality
	HCV Positive Group
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	HCV Positive Group
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	HCV Positive Group
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Investigations
Protocol deviation	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.