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)

NCT02358044 | Completed Phase 3 Results

• 2 other identifiers: 5172-0772014-003836-38
• Study Type: interventional
• Target: 257
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

• Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12)

  Hepatitis C Virus ribonucleic acid (HCV-RNA) levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR12 was defined as HCV RNA below the lower limit of quantification (\<LLOQ) at 12 weeks after the end of all study therapy. The primary efficacy hypothesis for this study was that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was non-inferior to the percentage in the SOF plus PR arm. A secondary statistical analysis was performed to determine whether the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was superior to the percentage in the SOF plus PR arm.

  12 weeks after end of all therapy (Study Week 24)

• Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period Plus First 14 Follow-up Days

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who experienced at least one AE was reported for each treatment arm.

  Treatment + First 14 days of follow-up (Up to Week 14)

• Percentage of Participants Discontinuing Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who discontinued study treatment due to an AE was reported for each treatment arm. Participants that discontinued study drug treatment due to an AE may have still continued on trial.

  Up to Week 12

Secondary Outcomes (3)

• Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days

  Treatment + First 14 days of follow-up (Up to Week 14)

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)

  24 weeks after end of all therapy (Study Week 36)

• Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4)

  4 weeks after end of all therapy (Study Week 16)

Study Arms (2)

Grazoprevir + Elbasvir

EXPERIMENTAL

Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.

Drug: Sofosbuvir; Biological: PegIntron; Drug: Ribavirin

SOF + PR

ACTIVE COMPARATOR

Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.

Drug: Grazoprevir/Elbasvir (100 mg/50 mg) FDC

Interventions

Sofosbuvir DRUG

400 mg tablets, taken orally (PO) every day (QD) for 12 weeks.

Grazoprevir + Elbasvir

PegIntron BIOLOGICAL

PegIntron administered subcutaneously every week (QW) at 1.5 mcg/kg for 12 weeks.

Grazoprevir + Elbasvir

Ribavirin DRUG

Capsule and/or tablet administered PO twice daily (BID) based on weight (1000 - 1200 mg) for 12 weeks.

Grazoprevir + Elbasvir

Grazoprevir/Elbasvir (100 mg/50 mg) FDC DRUG

Grazoprevir/Elbasvir (100 mg/50 mg) FDC, taken PO QD for 12 weeks.

SOF + PR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (5)

• 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.

  PMID: 27542322 RESULT

• 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.

  PMID: 30587935 DERIVED

• 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.

  PMID: 29461687 DERIVED

• 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.

  PMID: 29404492 DERIVED

• 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.

  PMID: 29344726 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; peginterferon alfa-2b; Ribavirin; grazoprevir; elbasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: February 27, 2015
• Primary Completion: November 26, 2015
• Study Completion: February 16, 2016
• Last Updated: October 3, 2018
• Results First Posted: January 11, 2017

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share