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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03098121
• Other study ID #: TYGH105034
• Status: Completed
• Phase: Phase 4
• Start date: October 20, 2017
• Est. completion date: November 30, 2018

Study information

• Verified date: December 2018
• Source: Taoyuan General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Coinfection
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• grazoprevir and elbasvir
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.

Locations

Country	Name	City	State
Taiwan	Taoyuan general hospital	Taoyuan

Sponsors (2)

Lead Sponsor	Collaborator
Taoyuan General Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Taiwan, 

References & Publications (9)

Bunchorntavakul C, Chavalitdhamrong D, Tanwandee T. Hepatitis C genotype 6: A concise review and response-guided therapy proposal. World J Hepatol. 2013 Sep 27;5(9):496-504. doi: 10.4254/wjh.v5.i9.496. Review. — View Citation

Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, Peters MG, Koziel MJ, Bhan AK, Alston B, Colquhoun D, Nevin T, Harb G, van der Horst C; AIDS Clinical Trials Group A5071 Study Team. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004 Jul 29;351(5):451-9. — View Citation

Laguno M, Cifuentes C, Murillas J, Veloso S, Larrousse M, Payeras A, Bonet L, Vidal F, Milinkovic A, Bassa A, Villalonga C, Pérez I, Tural C, Martínez-Rebollar M, Calvo M, Blanco JL, Martínez E, Sánchez-Tapias JM, Gatell JM, Mallolas J. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology. 2009 Jan;49(1):22-31. doi: 10.1002/hep.22598. Erratum in: Hepatology. 2009 Mar;49(3):1058. — View Citation

Liu CH, Sheng WH, Sun HY, Hsieh SM, Lo YC, Liu CJ, Su TH, Yang HC, Liu WC, Chen PJ, Chen DS, Hung CC, Kao JH. Peginterferon plus Ribavirin for HIV-infected Patients with Treatment-Naïve Acute or Chronic HCV Infection in Taiwan: A Prospective Cohort Study. Sci Rep. 2015 Nov 30;5:17410. doi: 10.1038/srep17410. — View Citation

Liu JY, Lin HH, Liu YC, Lee SS, Chen YL, Hung CC, Ko WC, Huang CK, Lai CH, Chen YS, Shih YL, Chung HC, Liang SH, Lin JN. Extremely high prevalence and genetic diversity of hepatitis C virus infection among HIV-infected injection drug users in Taiwan. Clin Infect Dis. 2008 Jun 1;46(11):1761-8. doi: 10.1086/587992. — View Citation

Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Bräu N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M; ION-4 Investigators. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21. — View Citation

Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, Matthews GV, Saag MS, Zamor PJ, Orkin C, Gress J, Klopfer S, Shaughnessy M, Wahl J, Nguyen BY, Barr E, Platt HL, Robertson MN, Sulkowski M. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015 Aug;2(8):e319-27. doi: 10.1016/S2352-3018(15)00114-9. Epub 2015 Jul 9. Erratum in: Lancet HIV. 2015 Aug;2(8):e316. Lancet HIV. 2015 Oct;2(10):e416. — View Citation

Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-García J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H Jr, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT; APRICOT Study Group. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004 Jul 29;351(5):438-50. — View Citation

Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, Sherman KE, Dretler R, Fishbein D, Gathe JC Jr, Henn S, Hinestrosa F, Huynh C, McDonald C, Mills A, Overton ET, Ramgopal M, Rashbaum B, Ray G, Scarsella A, Yozviak J, McPhee F, Liu Z, Hughes E, Yin PD, Noviello S, Ackerman P; ALLY-2 Investigators. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):714-25. doi: 10.1056/NEJMoa1503153. Epub 2015 Jul 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virological response	The proportion of sustained virological response 12 weeks after the end of therapy after the treatment of grazoprevir and elbasvir	12 weeks after the end of therapy
Secondary	Severe adverse effects	The frequency of severe adverse effects leading to discontinuation	during the treatment of grazoprevir and elbasvir