Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics

A Phase IV, Single Arm, Open-Label Study to Determine the Efficacy and Safety of Ledipasvir/Sofosbuvir (LDV/SOF) in Treatment-Naive Alcoholic Subjects With Chronic Genotype 1 Hepatitis C Infection

To determine the efficacy and safety of Harvoni in treatment-naïve alcoholic subjects with Genotype 1 HCV infection

Study Overview

• Status: Completed
• Conditions: Genotype 1 Hepatitis C Virus
• Intervention / Treatment: Drug: harvoni

Detailed Description

determine the cure rate of Harvoni in treatment naïve alcoholic subjects with Genotype 1 HCV infection

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 680017
      • University of Nebraska

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject must be willingly and able to provide written informed consent
2. Age 19 years of age or older (The age of consent in Nebraska)
3. HCV treatment-naïve, as defined as no prior exposure to any Interferon (IFN), RBV, or other FDA approved or experimental HCV-specific direct-acting antiviral agent
4. HCV RNA level at most 6 months prior to the Baseline/Day 1 visit.
5. HCV genotyping 1a, 1b, or mixed 1a/ab. Any non-definitive results will exclude the subject from study participation.
6. Alcohol misuse as defined by the Alcohol Use Disorders Identification Test (AUDIT) score subjects must score > 8 (associated with harmful or hazardous drinking)

7. Cirrhosis determination [up to 20% of study subjects may have cirrhosis]:

   1. Cirrhosis is defined as any one of the following:

      • History of a liver biopsy showing cirrhosis (e.g. Metavir score = 4 or Ishak score > 5)
      • Fibroscan showing cirrhosis or results > 12.5 kPa
      • FIBRO Spect II index consistent with F3 or F4 AND an AST : platelet ration index (APRI) of > 2 during Screening

   2. Absence of cirrhosis is defined as any one of the following:

      • Liver biopsy within 2 years of Screening showing absence of cirrhosis
      • Fibroscan within 6 months of Baseline/Day1 with a result of ≤ 12.5 kPa
      • FIBRO Spect II Index consistent with F0- F2 AND APRI of ≤ 1 during Screening
8. Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma HCC) is required

9. Subjects must have the following laboratory parameters at screening:

   1. ALT < 10 x the upper limit of normal (ULN)
   2. AST < 10 x ULN
   3. Direct bilirubin < 2.0 x ULN
   4. Platelets > 50,000
   5. HbA1c < 8.5%
   6. Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation
   7. Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects.
   8. Albumin ≥ 2.5 g/dL
   9. INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.
10. Subject has not been treated with any investigational drug or device within 30 days of the screening visit.

Exclusion Criteria:

1. Pregnant women and nursing mothers are ineligible due to the possible risk of adverse effects in the newborn. Eligible patients of reproductive potential should use adequate contraception if sexually active.
2. Serious concurrent medical illness which would jeopardize the ability of the subject to receive the therapy as outlined in this protocol with reasonable safety.
3. Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); subjects under evaluation for a malignancy are not eligible.
4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
5. Use of any prohibited concomitant medications within 30 days of the Baseline/Day 1 visit.
6. Known hypersensitivity to LDV/SOF

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Harvoni x 8 or 12 weeks; patient will receive 8 or 12 weeks depending on clinical data	Drug: harvoni; 8 or 12 weeks of harvoni therapy with monthly nursing visiting to monitor alcohol and adherence of harvoni therapy; Other Names: Ledipasvir/Sofosbuvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Subjects Who Achieve Negative RNA in Alcoholics	Sustained viral response in treatment -naive heavy alcohol drinking patients.	12 weeks after the end of Harvoni therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Advanced Fibrosis Score of F3/F4 Who Achieve SVR	Number of alcoholics with HCV type 1 genotype who had advanced fibrosis F3/F4 who achieve SVR	12 weeks after the end of Harvoni therapy

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Mark Mailliard, MD, UNMC

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimated): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: 0121-16-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: with Gilead Inc.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No