Clinical trial NCT02358044: Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077)
Official title: A Phase III, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 Versus Sofosbuvir/Pegylated Interferon/Ribavirin (PR) in Treatment-Naïve and PR Prior Treatment Failure Subjects With Chronic HCV GT1, 4 or 6 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study comparing grazoprevir (MK-5172) plus elbasvir (MK-8742) treatment with sofosbuvir (SOF) plus Pegylated Interferon plus Ribavirin (RBV) \[PR\] treatment in treatment-naïve and prior PR treatment failure participants with chronic Hepatitis C Virus (HCV) genotype (GT)1, GT4, or GT6 infection. The primary objectives are to compare efficacy (assessed by the percentage of participants achieving sustained virologic response 12 weeks after ending study treatment \[SVR12\]) and safety between the grazoprevir plus elbasvir treatment arm and the SOF plus PR treatment arm. The primary hypothesis is that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir treatment arm is non-inferior to that in the SOF plus PR treatment arm.


Eligibility criteria: Inclusion Criteria:

* Weigh ≥40 kg and ≤125 kg
* documented chronic HCV GT1, GT4, or GT6 infection
* cirrhosis/absence of cirrhosis defined by liver biopsy, Fibroscan, or FibroSure®
* either treatment naïve or PR Null Responder, PR Partial Responder, or PR Prior Relapser
* participant and partner both agree to use at least use at least 2 effective methods of contraception from at least 2 weeks prior to Day 1 and continue until up to 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion Criteria:

* has evidence of decompensated liver disease
* is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
* history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy
* has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
* has any of the following conditions: immunologically-mediated disease, organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial, history of chronic hepatitis not caused by HCV

Primary outcomes:
measure: Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12)
timeFrame: 12 weeks after end of all therapy (Study Week 24)
measure: Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period Plus First 14 Follow-up Days
timeFrame: Treatment + First 14 days of follow-up (Up to Week 14)
measure: Percentage of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to Week 12
Secondary outcomes:
measure: Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days
timeFrame: Treatment + First 14 days of follow-up (Up to Week 14)
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
timeFrame: 24 weeks after end of all therapy (Study Week 36)
measure: Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4)
timeFrame: 4 weeks after end of all therapy (Study Week 16)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Sperl J, Horvath G, Halota W, Ruiz-Tapiador JA, Streinu-Cercel A, Jancoriene L, Werling K, Kileng H, Koklu S, Gerstoft J, Urbanek P, Flisiak R, Leiva R, Kazenaite E, Prinzing R, Patel S, Qiu J, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Platt HL. Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial. J Hepatol. 2016 Dec;65(6):1112-1119. doi: 10.1016/j.jhep.2016.07.050. Epub 2016 Aug 16.
citation: Ng X, Nwankwo C, Arduino JM, Corman S, Lasch KE, Lustrino JM, Patel S, Platt HL, Qiu J, Sperl J. Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir. Patient Prefer Adherence. 2018 Dec 11;12:2631-2638. doi: 10.2147/PPA.S172732. eCollection 2018.
citation: Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.
citation: Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.
citation: Zeuzem S, Serfaty L, Vierling J, Cheng W, George J, Sperl J, Strasser S, Kumada H, Hwang P, Robertson M, Wahl J, Barr E, Talwani R, Platt H. The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection. J Gastroenterol. 2018 May;53(5):679-688. doi: 10.1007/s00535-018-1429-3. Epub 2018 Jan 17.