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Efficacy and Tolerability of Grazoprevir and Elbasvir in Patients With Chronic Genotype 1 HCV and HIV Co-infection

Primary Purpose

Chronic Hepatitis C

Status

Completed

Phase

Phase 4

Locations

Taiwan

Study Type

Interventional

Intervention

grazoprevir and elbasvir

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men and non-pregnant women, at least 20 years of age with chronic genotype 1 HCV and HIV co-infection.
HCV RNA > 10,000 IU/mL
Stable antiretroviral therapy (ARV) with confirmed plasma HIV-1 RNA < 200 copies/mL
CD4 T-cell count > 100 cells/L
peginterferon alfa plus ribavirin failure: null response <1 log10 IU/mL reduction in HCV RNA at week 4; detectable HCV RNA since week 12 to the end of treatment; detectable HCV RNA for 12 to 24 weeks after the end of treatment; or discontinuation of peginterferon alfa plus ribavirin due to grade 3 or grade 4 adverse effects at any moment.

Exclusion Criteria:

Decompensated liver disease (presence or history of ascites, oesophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs of advanced liver diseases)
Liver cirrhosis with Child-Pugh class B or C, or with a Child-Turcotte-Pugh score of more than 6 points and albumin below 3 g/dL or platelet count below 75,000/ μL
History of malignant disease, or evidence of hepatocellular carcinoma
ARV with protease inhibitor containing regimen HBsAg and HBV core antibody should be checked in all patients. HBsAg positive patients should be excluded from the study. HBV core antibody positive patients should be closely monitored for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Appropriate patient management should be instituted for HBV infection as clinically indicated.

Sites / Locations

Taoyuan general hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Genotype 1 HCV and HIV co-infection

Arm Description

Patients with chronic Genotype 1 HCV and HIV co-infection, with or without resistance-associated substitution (RAS) of NS5A, received grazoprevir and elbasvir in a fixed-dose combination tablet once daily with ribavirin for 16 weeks, and patients with chronic genotype 1b received grazoprevir and elbasvir once daily for 12 weeks.

Outcomes

Primary Outcome Measures

Sustained virological response

The proportion of sustained virological response 12 weeks after the end of therapy after the treatment of grazoprevir and elbasvir

Secondary Outcome Measures

Severe adverse effects

The frequency of severe adverse effects leading to discontinuation

Full Information

NCT ID

NCT03098121

First Posted

March 27, 2017

Last Updated

December 18, 2018

Sponsor

Taoyuan General Hospital

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03098121

Brief Title

Efficacy and Tolerability of Grazoprevir and Elbasvir in Patients With Chronic Genotype 1 HCV and HIV Co-infection

Official Title

Efficacy and Tolerability of Grazoprevir and Elbasvir in Peginterferon Alfa Plus Ribavirin Experienced Patients With Chronic Genotype 1 HCV and HIV Co-infection: a Non-randomised, Open-label Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

October 20, 2017 (Actual)

Primary Completion Date

November 30, 2018 (Actual)

Study Completion Date

November 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Taoyuan General Hospital

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

This clinical study will evaluate whether grazoprevir and elbasvir is efficacious, safe, and well-tolerated in peginterferon alfa plus ribavirin experienced patients who inject drugs (PWID) and men who sex with men (MSM) with genotype 1 HCV and HIV co-infection.

Detailed Description

Primary Objective •To assess the efficacy of grazoprevir 100mg and elbasvir 50mg by determining the proportion of sustained virological response 12 weeks after the end of therapy (SVR12; HCV RNA concentration less than 10 IU/ mL at follow-up week 12) in peginterferon alfa plus ribavirin experienced patients with genotype 1 HCV and HIV co-infection, compared with treatment-naïve patients with 1 HCV and HIV co-infection. Secondary Objective •To assess the tolerability of grazoprevir 100mg and elbasvir 50mg in peginterferon alfa plus ribavirin experienced patients by measuring frequency of SAEs and AEs leading to discontinuation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Genotype 1 HCV and HIV co-infection

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

grazoprevir and elbasvir

Intervention Description

For patients with chronic genotype 1a, with or without resistance associated variant (RAV) of NS5A, are expected to receive grazoprevir and elbasvir in a fixed-dose combination tablet once daily with ribavirin for 16 weeks, and for patients with chronic genotype 1b are expected to receive grazoprevir and elbasvir in a fixed-dose combination tablet once daily for 12 weeks.

Primary Outcome Measure Information:

Title

Sustained virological response

Description

The proportion of sustained virological response 12 weeks after the end of therapy after the treatment of grazoprevir and elbasvir

Time Frame

12 weeks after the end of therapy

Secondary Outcome Measure Information:

Title

Severe adverse effects

Description

The frequency of severe adverse effects leading to discontinuation

Time Frame

during the treatment of grazoprevir and elbasvir

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and non-pregnant women, at least 20 years of age with chronic genotype 1 HCV and HIV co-infection. HCV RNA > 10,000 IU/mL Stable antiretroviral therapy (ARV) with confirmed plasma HIV-1 RNA < 200 copies/mL CD4 T-cell count > 100 cells/L peginterferon alfa plus ribavirin failure: null response <1 log10 IU/mL reduction in HCV RNA at week 4; detectable HCV RNA since week 12 to the end of treatment; detectable HCV RNA for 12 to 24 weeks after the end of treatment; or discontinuation of peginterferon alfa plus ribavirin due to grade 3 or grade 4 adverse effects at any moment. Exclusion Criteria: Decompensated liver disease (presence or history of ascites, oesophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs of advanced liver diseases) Liver cirrhosis with Child-Pugh class B or C, or with a Child-Turcotte-Pugh score of more than 6 points and albumin below 3 g/dL or platelet count below 75,000/ μL History of malignant disease, or evidence of hepatocellular carcinoma ARV with protease inhibitor containing regimen HBsAg and HBV core antibody should be checked in all patients. HBsAg positive patients should be excluded from the study. HBV core antibody positive patients should be closely monitored for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Appropriate patient management should be instituted for HBV infection as clinically indicated.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chien-Yu Cheng

Organizational Affiliation

Taoyuan General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Taoyuan general hospital

City

Taoyuan

ZIP/Postal Code

33004

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The study will be conducted at 3 different hospitals, and the investigators will share the data with other researchers every 3 months

IPD Sharing Time Frame

The data will become available in March 2019.

IPD Sharing Access Criteria

The investigators will share the data and outcome via international conference

Citations:

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19085908

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Efficacy and Tolerability of Grazoprevir and Elbasvir in Patients With Chronic Genotype 1 HCV and HIV Co-infection

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