Safety and Efficacy of Grazoprevir and Elbasvir for GT1ang GT6 With and Without HIV

February 11, 2020 updated by: The HIV Netherlands Australia Thailand Research Collaboration

Safety and Fibrosis Improvement of Grazoprevir and Elbasvir for HCV GT1 and GT6 With or Without HIV

This study will evaluate the safety and efficacy of combination treatment with grazoprevir + elbasvir for compensated cirrhotic participants with chronic genotype 1 (GT1) and genotype 6 (GT6) hepatitis C virus (HCV) infection with or without human immunodeficiency virus (HIV) infection.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Total 100 patients with compensated cirrhosis, chronically infected with HCV GT1 or GT6 with or without HIV infection will be included. Patients with HCV GT1 and GT6 will be enrolled on a 1:1 basis (approximately 50 patients with GT1 and 50 patients with GT6). Treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks. Treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks. The dosages of study drugs are 100 mg of grazoprevir once daily and 50 mg of elbasvir once daily. All patients will follow up to assess SVR (defined by HCV RNA level <12 IU/mL) at week12 and week 24 after treatment (SVR12 and SVR24, respectively). Additionally, participants will be evaluated the longitudinal changes in LS values by TE up to 240 weeks (5 years) after treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Bangkok, Thailand, 10330
        • Faculty of Medicine, Chulalongkorn University
      • Bangkok, Thailand, 10330
        • HIV-NAT, Thai Red Cross AIDS Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and women aged 18 years or older
  2. Documented chronic HCV GT1 or GT6 (positive for anti-HCV antibody and HCV RNA at least 6 months prior to screening)
  3. HCV RNA of at least 10,000 IU/ml
  4. Cirrhosis defined by: liver biopsy showing cirrhosis METAVIR F4; or TE showing cirrhosis with a result of >13.0 kPa
  5. Treatment-naïve individuals for chronic HCV infection
  6. Treatment-experienced individuals (Previous treatment failure with PEG-IFN plus RBV) for chronic HCV infection

  7. HIV-infected participants enrolled in this study must meet following criteria:

    7.1 Documented HIV infection 7.2 Naïve to treatment with any antiretroviral therapy (ART) or on HIV ART for at least 8 weeks prior to study entry using a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) 7.3 CD4+ T-cell count >200 cells/mm3 if on ART or >500 cell/mm3 if ART treatment naïve 7.4 Undetectable plasma HIV-RNA at least 8 weeks prior to screening if on ART or <50,000 copies/mL if ART treatment naïve

  8. Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential).

Exclusion Criteria:

  1. Evidence of decompensated liver disease (Child-Pugh Class B or C or Child-Pugh score >6, platelets less than 75 × 10³/μL, serum albumin < 3·0 g/dL, presence of or history of ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease)
  2. Co-infected with hepatitis B virus
  3. Has cirrhosis and liver imaging within 6 months showing evidence of HCC or is under evaluation for HCC
  4. Pregnant or breast-feeding from day 1 or anytime during treatment, and 14 days after the last dose of study medication
  5. Any medical condition requiring or likely to require chronic systemic administration of corticosteroids or other immunosuppressant drugs during the course of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HCV mono-infection Treatment naives
HCV treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.
Drug: Grazaoprevir/Elbasavir
treatment naive
Experimental: HCV mono-infection Treatment experienced
HCV treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.
Drug: Grazaoprevir/Elbasavir/RBV
treatment experienced
Experimental: HCV/HIV co-infection Treatment naives
HCV/HIV coinfected, treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.
Drug: Grazaoprevir/Elbasavir
treatment naive
Experimental: HCV/HIV co-infection Treatment experienced
HCV/HIV co-infected treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.
Drug: Grazaoprevir/Elbasavir/RBV
treatment experienced

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of SVR12
Time Frame: 12 weeks post-treatment
To evaluate the rate of sustained virological response (SVR) at 12 weeks after the end of treatment (SVR12) in compensated cirrhotic participants with GT1 and GT6 HCV infection with or without HIV infection treated with the combination of grazoprevir and elbasvir
12 weeks post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of SVR24
Time Frame: 24 weeks post-treatment
To evaluate the rate of sustained virological response (SVR) at 24 weeks after the end of treatment (SVR24)
24 weeks post-treatment
Decline of liver stiffness
Time Frame: 5 years post-treatment
To evaluate the percentage of participants achieving a significant decline in liver stiffness (LS) values (defined as a ≥30% decrease from baseline) up to 240 weeks (5 years) after treatment
5 years post-treatment
changes in liver stiffness
Time Frame: 5 years
To compare the longitudinal changes in LS values over time between participants and untreated historical controls
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

Merck Sharp & Dohme LLC
Chulalongkorn University

Investigators

  • Principal Investigator: Pisit Tangkijvanich, MD, Chulalongkorn University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2018

Primary Completion (Anticipated)

December 31, 2020

Study Completion (Anticipated)

December 31, 2020

Study Registration Dates

First Submitted

January 27, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimate)

January 31, 2017

Study Record Updates

Last Update Posted (Actual)

February 13, 2020

Last Update Submitted That Met QC Criteria

February 11, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HIV-NAT 245

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

only when needed as per the auditing/monitoring processes and requirement

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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