Viral Kinetics, Interferon Stimulated Genes (ISGs) and mirRNA Among Subjects Infected With Different Hepatitis C Virus Genotypes During Therapy With Sofosbuvir and GS-5816

NCT02468648 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 15014315-DK-0143
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Chronic hepatitis C is a serious liver disease. Current treatments have side effects. New drugs have been developed, but they work better in some people than others. Researchers want to learn why. Objective: \- To learn why new hepatitis C drugs sometimes do not work. Also, to learn if these drugs are safe and how well they work in people with different virus strains. Eligibility: \- Adults age 18 and older who are infected with hepatitis C virus genotypes 1-4 and who have either never been treated or treated previously with an interferon regimen (with or without ribavirin) that failed to clear the virus. Design:

• Participants will be screened with medical history and physical exam. They will have blood and urine tests and complete questionnaires.
• Participants will have a Fibroscan, an ultrasound that measures liver stiffness and other liver scans. They will have an electrocardiogram.
• Eligible participants will have a liver biopsy.
• Participants will be admitted to the Clinical Center. They will have a physical exam and blood tests, and complete questionnaires.
• They will take the first study drug dose as a tablet taken once daily.
• Participants will take the drug at home for 12 weeks.
• Participants will have 6 study visits. They will have blood and vital signs taken, and complete questionnaires.
• At week 4, participants will have another liver biopsy.
• After their last drug dose, participants will have 5 follow-up visits. They will have blood and vital signs taken, and complete questionnaires. They will discuss their medications and side effects. They may have another Fibroscan.

Conditions

Chronic Hepatitis C

Keywords

Oral Therapy; Liver Biopsy; Chronic Hepatitis C

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Sustained Virologic Response

  Absence of detectable virus 12 weeks after completion of antiviral therapy

  12 weeks

• Number of Participants Who Maintained HCV RNA Levels in Liver and Serum Less Than Lower Limit of Quantification (LLOQ)

  4 weeks

Secondary Outcomes (2)

• Number of Participants Who Sustained Virologic Response

  24 weeks

• Number of Participants Who Maintained HCV RNA Levels in Liver and Serum Less Than Lower Limit of Quantification (LLOQ)

  24 weeks

Study Arms (1)

Combination of sofosbuvir and GS-5816

EXPERIMENTAL

Combination of sofosbuvir and GS-5816 agent into a single pill will be used.

Drug: Sofosbuvir; Drug: GS-5816

Interventions

Sofosbuvir DRUG

An NS5B polymerase inhibitor that is already approved for use in combination with interferon and ribavirin for the treatment of HCV genotype 1 infection

Combination of sofosbuvir and GS-5816

GS-5816 DRUG

An NS5A replication complex inhibitor with potent activity against most strains of hepatitis C virus.

Combination of sofosbuvir and GS-5816

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Male or female, age greater than or equal to18 years.
• Body mass index (BMI) greater than or equal to 18 kg/m\^2.
• HCV RNA greater than or equal to10\^4 IU/mL at Screening
• HCV genotypes 1a, 1b, 2, 3 or 4 at screening
• Confirmation of chronic HCV infection documented by either:
• A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or
• A liver biopsy performed within 12 weeks prior to the Baseline/Day 1 visit with evidence of chronic HCV infection. A prior biopsy would be acceptable if performed with 12 weeks AND liver tissue stored in RNALater was available.
• Screening ECG without clinically significant abnormalities.
• Subjects must have the following laboratory parameters at screening:
• ALT less than or equal to 10 times the upper limit of normal (ULN)
• AST less than or equal to 10 times ULN
• Direct bilirubin less than or equal to 1.5 ULN
• Platelets \> 70,000
• HbA1c less than or equal to8.5%

You may not qualify if:

• Current or prior history of any of the following:
• Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.
• Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
• Solid organ transplantation.
• Significant pulmonary disease, significant cardiac disease or porphyria.
• Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to randomization or has not required medication in the last 12 months may be included.
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible.
• Significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Any prior treatment with a direct acting antiviral agent (protease inhibitors, NS5A inhibitors and NS5B polymerase inhibitors/non-nucleoside polymerase inhibitors.)
• Pregnant or nursing female or male with pregnant female partner.
• Chronic liver disease of a non HCV etiology (e.g., hemochromatosis, Wilson s disease, alfa 1 antitrypsin deficiency, cholangitis).
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
• Clinically-relevant drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Sofosbuvir; velpatasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Marc Ghany, MD, MHSc
• Organization: NIDDK

marcg@intra.niddk.nih.gov

301-402-5115

Study Officials

• Marc G Ghany, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2015
• First Posted: June 11, 2015
• Study Start: June 9, 2015
• Primary Completion: September 14, 2018
• Study Completion: September 14, 2018
• Last Updated: March 19, 2020
• Results First Posted: March 19, 2020

Record last verified: 2018-09-14

Locations

US (1)