Phase 3
Completed N=420
Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) With or Without Ribavirin for Participants With Hepatitis C Genotype 1, 4, or 6 Infections Who Have Failed Prior Treatment With Pegylated Interferon + Ribavirin (MK-5172-068)
Hepatitis C Infection
Source: ClinicalTrials.gov NCT02105701 ↗
Enrolled (actual)
420
Serious AEs
5.7%
Results posted
Mar 2016
Primary outcomePrimary: Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12) — 92.4; 94.2; 92.4; 98.1 Percentage of participants — p=<0.001
Summary
This is an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) with or without ribavirin (RBV) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infections who have failed prior therapy with pegylated interferon and RBV. The primary study hypothesis is that in at least one of the study arms, the percentage of participants achieving sustained viral response 12 weeks after the end of all study treatment (SVR12) will be superior to 58%.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12) |
92.4; 94.2; 92.4; 98.1 | <0.001 sig |
| PRIMARY Number of Participants Experiencing Adverse Events (AE) |
74; 85; 77; 95 | — |
| PRIMARY Number of Participants Discontinuing Study Treatment Due to an AE |
1; 1; 0; 5 | — |
| SECONDARY Percentage of Participants Achieving Undetectable HCV RNA 24 Weeks After the End of All Treatment (SVR24) |
91.4; 94.2; 89.5; 95.3 | <0.001 sig |
Eligibility Criteria
Inclusion Criteria
- Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typable or mixed genotype infection (positive for anti-HCV antibody, HCV ribonucleic acid [RNA], or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
- Cirrhosis defined as liver biopsy showing METAVIR F4; or Fibroscan showing result >12.5 kilopascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST):platelet ratio index (APRI) of >2
- Absence of cirrhosis defined as liver biopsy showing absence of cirrhosis; or Fibroscan result of ≤ 12.5 kPa; or Fibrosure® (Fibrotest®) score of ≤ 0.48 and APRI ≤ 1
- Previous HCV treatment status of peginterferon/RBV Null responder; or peginterferon/RBV Partial responder; or peginterferon/RBV Treatment Relapse
- For human immunodeficiency virus (HIV) co-infected participants: documented HIV-1 infection; currently naïve to treatment with any antiretroviral therapy (ART) and have no plans to initiate ART treatment while participating in this study; or be on HIV ART for at least 8 weeks prior to study entry (dual nucleoside reverse transcriptase inhibitor [NRTI] backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) (no changes in HIV regimen allowed within 4 weeks of randomization); cluster of differentiation 4 (CD4)+ T-cell count >200 cells/mm^3 at screening; documented undetectable plasma HIV-1 RNA at least 8 weeks prior to screening; participants not on ART, HIV RNA must be 6, must be excluded
- Co-infected with hepatitis B virus
- Has had previous direct-acting antiviral treatment
- History of malignancy <=5 years prior except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy
- Has cirrhosis and liver imaging showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
- Taking or plans to take any HIV therapy that includes a ritonavir-boosted or unboosted protease inhibitor, efavirenz or etravirine
- Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
- Clinically-relevant drug or alcohol abuse within 12 months
- Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; or is a male whose female partner(s) is/are pregnant
- History of organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
- Poor venous access
- History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
- Hemoglobinopathy, including, but not limited to, thalassemia major
- Any medical condition requiring, or likely to require, chronic systemic corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial
- For participants with HIV, history of opportunistic infection in the preceding 6 months
- For participants with HIV, use of HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine)
- Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
Data sourced from ClinicalTrials.gov (NCT02105701). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.