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NCT02105454

Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048)

Completed Phase 2 Results posted Last updated 24 September 2018
What this trial tests

Phase 2 trial testing Grazoprevir (GZR) in Hepatitis C Virus in 79 participants. Completed in 4 May 2015.

Timeline
23 May 2014
Primary endpoint
4 May 2015
4 May 2015

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment79
Start date23 May 2014
Primary completion4 May 2015
Estimated completion4 May 2015

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Hepatitis C Virus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12) Primary · Up to 24 weeks

SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.

GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks97.190.1 – 99.7
Percentage of Participants Experiencing Adverse Events Primary · Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)

Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks79.769.2 – 88.0
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event Primary · Up to 12 weeks

Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks1.30.0 – 6.9
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy Secondary · Up to 24 weeks

SVR12 is defined as participants having HCV RNA level lower than the LLoQ (\<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.

Boceprevir with signature baseline RAVs, n=9
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks88.951.8 – 99.7
Boceprevir without signature baseline RAVs, n=16
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks100.079.4 – 100.0
Telaprevir with signature baseline RAVs, n=18
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks94.472.7 – 99.9
Telaprevir without signature baseline RAVs, n=22
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks100.084.6 – 100.0
Simeprevir with signature baseline RAVs, n=4
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks100.039.8 – 100.0
Simeprevir without signature baseline RAVs, n=1
GroupValue95% CI
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks100.02.5 – 100.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
Serious: 6/79 (8%)
Deaths:

Serious adverse events (6 terms)

ReactionSystemGZR 100 mg + EBR 50 mg + R…
AppendicitisInfections and infestations
Pharyngitis bacterialInfections and infestations
Urinary tract infectionInfections and infestations
Laryngeal squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Inguinal herniaGastrointestinal disorders
Other adverse events (11 terms — click to expand)

ReactionSystemGZR 100 mg + EBR 50 mg + R…
FatigueGeneral disorders
HeadacheNervous system disorders
AstheniaGeneral disorders
NauseaGastrointestinal disorders
InsomniaPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Haemoglobin decreasedInvestigations

Most-reported serious reactions: Appendicitis, Pharyngitis bacterial, Urinary tract infection, Laryngeal squamous cell carcinoma, Chronic obstructive pulmonary disease, Inguinal hernia.

Data from ClinicalTrials.gov NCT02105454 adverse events section.

Sponsor's own description

In this study, participants with hepatitis C virus (HCV) genotype 1 (GT1) who failed prior direct-acting antiviral (DAA) therapy will receive Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) to evaluate sustained virologic response (SVR) using this drug combination.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE.
    Buti M, Gordon SC, Zuckerman E, Lawitz E, et al · · 2016 · cited 74× · PMID 26371152 · DOI 10.1093/cid/civ722
  2. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis.
    Jacobson IM, Lawitz E, Kwo PY, Hézode C, et al · · 2017 · cited 59× · PMID 28193518 · DOI 10.1053/j.gastro.2017.01.050
  3. Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis.
    Yao Y, Yue M, Wang J, Chen H, et al · · 2017 · cited 4× · PMID 28164081 · DOI 10.1155/2017/8186275

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