deLIVER: Direct Acting Antiviral Effects on the Liver

NCT02938013 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00110677
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, partially-randomized plasma and liver sampling study to assess hepatitis C virus (HCV) kinetics during treatment with two (Sofosbuvir/Velpatasvir) or three (Sofosbuvir/Velpatasvir/Voxilaprevir) direct acting antivirals (DAAs)

Conditions

HCV Coinfection; Liver Disease; HIV

Outcome Measures

Primary Outcomes (1)

• Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy

  Estimate the total number of HCV-infected Hepatocytes (virus burden) for each participant between pre-treatment liver biopsy and post treatment liver biopsy samples using HCV Quantitative real time PCR. Comparison of total number of HCV-infected Hepatocytes (virus burden) were reported between HCV mono infection and co infection groups.

  Pre-treatment, Day 7

Secondary Outcomes (3)

• Reduction Over the First Week in Plasma HCV RNA

  Pre-treatment, up to 1 week

• Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM).

  Pre-treatment, up to 1 week

• Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy.

  Pre-treatment, after first week

Study Arms (3)

Group A

EXPERIMENTAL

Monoinfected: Sofosbuvir/Velpatasvir/Voxilaprevir SOF/VEL/VOX days 0-7 Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL days 8 (week 2) through 84 (week 12). Post-treatment follow up through week 12.

Drug: Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX]

Group B

ACTIVE COMPARATOR

Monoinfected: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12.

Drug: Sofosbuvir/Velpatasvir (SOF/VEL)

Group C

ACTIVE COMPARATOR

HIV/HCV Co-infection: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12.

Drug: Sofosbuvir/Velpatasvir (SOF/VEL)

Interventions

Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX] DRUG

antiviral therapy for HCV

Group A

Sofosbuvir/Velpatasvir (SOF/VEL) DRUG

antiviral therapy for HCV

Group B; Group C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness of participant to provide written informed consent.
• Men and women age ≥18 to ≤70 years at study entry
• Body mass index (BMI) ≥ 18 kg/m2
• HCV RNA ≥ 10,000 IU/mL at Screening
• HCV genotype 1a at Screening or within 6 months of screening
• Chronic HCV infection (≥ 6 months) documented by prior medical history
• HCV treatment-naïve with no prior treatment with any IFN, RBV, or approved or experimental HCV-specific DAA
• Absence of cirrhosis as defined as transient elastography (FibroScan®) liver stiffness measurement \< 12.5 kPa within 6 months of screening
• The following laboratory values obtained within 42 days prior to study entry. • Hemoglobin \> 10 g/dL for men and \> 9 g/dL for women
• Platelet count ≥90,000/mm3
• International normalized ratio (INR) ≤1.5
• Calculated creatinine clearance (CrCl) ≥ 30 mL/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase level ≤ 10 x upper limit of the normal range (ULN)
• Total bilirubin \<3 mg/dL
• Albumin ≥3.5 g/dL

You may not qualify if:

• Breastfeeding.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
• Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry.
• Active hepatitis B infection (positive HBsAg) within 42 days prior to study entry.
• History of decompensated liver disease (including but not limited to encephalopathy, variceal bleeding, or ascites) prior to study entry.
• Any cause of liver disease other than chronic HCV infection, including but not limited to the following:
• Hemochromatosis
• Alpha-1 antitrypsin deficiency
• Wilson's disease
• Autoimmune hepatitis
• Alcoholic liver disease
• Drug-related liver disease
• Uncontrolled or active depression or other psychiatric disorder within 24 weeks prior to study entry that in the opinion of the investigator might preclude adherence to study requirements.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Serious illness including uncontrolled seizure disorders, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the investigator might preclude completion of the protocol.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital : The John G. Bartlett Specialty Practice

Baltimore, Maryland, 21287, United States

Location

Related Publications (2)

• Sachithanandham J, Leep-Lazar J, Quinn J, Bowden K, Balasubramaniam P, Ward K, Ribeiro RM, Sulkowski MS, Balagopal A. Direct-Acting Antivirals Quickly Eradicate Hepatitis C Virus From the Liver in People With Human Immunodeficiency Virus but Do Not Fully Reverse Immune Activation. J Infect Dis. 2025 Jun 2;231(5):1299-1308. doi: 10.1093/infdis/jiae598.

  PMID: 39656808 DERIVED

• Sachithanandham J, Balagopal A, Leep-Lazar J, Quinn J, Bowden K, Ward K, Ribeiro RM, Sulkowski MS. Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus. J Infect Dis. 2023 Aug 11;228(3):311-320. doi: 10.1093/infdis/jiad025.

  PMID: 36722133 DERIVED

MeSH Terms

Conditions

Liver Diseases

Interventions

Sofosbuvir; velpatasvir

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Limitations and Caveats

This study is based on a relatively small sample of the liver

Results Point of Contact

• Title: Dr. Mark Sulkowski
• Organization: Johns Hopkins University School of Medicine

msulkowski@jhmi.edu

443-997-1900

Study Officials

• Mark Sulkowski, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 19, 2016
• Study Start: January 1, 2017
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2020
• Last Updated: February 24, 2022
• Results First Posted: November 16, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)