Hepatitis C (HCV) Cure and Kidney Health

HCV Cure and Kidney Health: A Prospective, Observational Cohort Study of HCV Genotype 1 and 4 Infected Adults With and Without HIV Infection

The purpose of this study is to learn how 12 weeks of HCV treatment with elbasvir and grazoprevir (brand name Zepatier) impacts your kidney function.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]

Detailed Description

Prospective data collection of 25 Genotype 1 or 4 HCV-infected women from the San Francisco Women's Interagency HIV Study (WIHS) site and 25 Genotype 1 or 4 HCV-infected men from the San Francisco VA Medical Center who are initiated on Zepatier for 12 weeks (Total n=50). For women and men with HCV genotype 1a infection, only those without baseline NS5A resistance mutations will be included. Blood/urine samples will be collected before initiation of treatment, 4 weeks after treatment initiation, 12 weeks after treatment initiation (end of treatment), 24 weeks after treatment initiation to determine Sustained Virological Response (SVR), and at 48 weeks after treatment initiation.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • Recruiting
      • San Francisco VA Medical Center
      • Contact: Phyllis C Tien, MD; Phone Number: 22577 415-221-4810; Email: phyllis.tien@ucsf.edu
      • Contact: Heather Freasier, MS; Phone Number: 415-379-5518; Email: heather.freasier@ucsf.edu
    • San Francisco, California, United States, 94115
      • Enrolling by invitation
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

25 Genotype 1 or 4 HCV-infected women from the San Francisco WIHS site and 25 Genotype 1 or 4 HCV-infected men from the San Francisco VA Medical Center

Description

Inclusion Criteria:

1. Active Genotype 1 or 4 HCV infection (If with Genotype 1a infection, only those without baseline NS5A resistance mutation will be included; Genotype 4 HCV infection is uncommon in both study populations). Subjects with HIV coinfection are included. We will not exclude patients who have severe Chronic Kidney Disease, are on dialysis, or have undergone kidney transplant.

Exclusion Criteria:

1. HCV genotype 2, 3, 5, or 6 infection
2. Previous virologic failure to regimens containing an NS5A inhibitor
3. Decompensated liver disease (Child-Pugh Class B or C)
4. Albumin below 3g/dL
5. Platelet count below 75,000
6. Any condition that the investigator considers a contraindication to study participation including limited life expectancy
7. Pregnant or breastfeeding woman
8. Hepatitis B virus (HBV) surface antigen positive (Note: Patients positive for the HBV core antibody will not be excluded, but will have HBV DNA levels checked and will be monitored while on Direct Acting Antivirals (DAA) therapy and medically managed as considered appropriate)
9. Documented ongoing nonadherence to prescribed medications or medical treatment, failure to complete HCV disease evaluation appointments and procedures or unable to commit to scheduled followup/monitoring for the duration of treatment
10. Poor venous access not allowing screening laboratory collection
11. Known hypersensitivity to elbasvir/grazoprevir
12. Co-administration with drugs that are 1) strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin); 2) OATP1B1/3 inhibitors (e.g., cyclosporine, darunavir, atazanavir, tipranavir, lopinavir or saquinavir) or 3) efavirenz

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glomerular filtration rate and injury	measured by Cystatin C	1 year
glomerular filtration rate and injury	measured by Creatinine	1 year
glomerular filtration rate and injury	measured by albuminuria	1 year
Tubule dysfunction	measured by α1-microglobulin	1 year
Tubule dysfunction	measured by beta2-microglobulin	1 year
Tubule injury	measured by Interleukin-18	1 year
tubule injury	measured by Kidney injury molecule-1	1 year
tubule injury	measured by Neutrophil gelatinase-associated lipocalcin (NGAL)	1 year
tubule injury	measured by Clusterin	1 year
tubule injury	measured by Trefoil factor-3 (TFF-3)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HCV clearance	measured by HCV viral load	1 year
liver fibrosis	liver stiffness measured by transient elastography	1 year

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Phyllis C Tien, MD, San Francisco VA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: January 9, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: genotype 1; genotype 4
• 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; Grazoprevir; Elbasvir-grazoprevir drug combination
• Other Study ID Numbers: 17-22790

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes