- ICH GCP
- US Clinical Trials Registry
- 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)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Grazoprevir + Elbasvir
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.
|
400 mg tablets, taken orally (PO) every day (QD) for 12 weeks.
PegIntron administered subcutaneously every week (QW) at 1.5 mcg/kg for 12 weeks.
Capsule and/or tablet administered PO twice daily (BID) based on weight (1000 - 1200 mg) for 12 weeks.
|
Active Comparator: SOF + PR
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.
|
Grazoprevir/Elbasvir (100 mg/50 mg) FDC, taken PO QD for 12 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12)
Time Frame: 12 weeks after end of all therapy (Study Week 24)
|
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
Time Frame: Treatment + First 14 days of follow-up (Up to Week 14)
|
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
Time Frame: Up to Week 12
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days
Time Frame: Treatment + First 14 days of follow-up (Up to Week 14)
|
Tier 1 safety events were pre-specified by the protocol to evaluate safety and test the safety superiority hypothesis.
Tier 1 safety events were chosen to assess broad tolerability, hematological side effects and liver-related laboratory abnormalities.
For this study, Tier 1 safety events included: any serious drug-related AE, any drug-related AE leading to permanent discontinuation (DC) of all study drugs, neutrophil count <0.75 x 10^9/L, hemoglobin <10 g/dL, severe depression, hepatic events of clinical interest (defined by abnormal increases in alanine aminotransferase [ALT], aspartate aminotransferase [AST], or alkaline phosphatase [ALP]), or events meeting stopping rule criteria for DC from trial (due to abnormal increases of ALT, AST, or ALP with/without pre-specified related AEs).
The percentage of participants who experienced each individual event that was defined as a Tier 1 safety event during the study treatment period was reported for each treatment arm.
|
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)
Time Frame: 24 weeks after end of all therapy (Study Week 36)
|
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.
SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy.
|
24 weeks after end of all therapy (Study Week 36)
|
Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4)
Time Frame: 4 weeks after end of all therapy (Study Week 16)
|
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.
SVR4 was defined as HCV RNA <LLOQ at 4 weeks after the end of all study therapy.
|
4 weeks after end of all therapy (Study Week 16)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis
- Hepatitis A
- Hepatitis C
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Sofosbuvir
- Ribavirin
- Peginterferon alfa-2b
- Grazoprevir
- Elbasvir-grazoprevir drug combination
Other Study ID Numbers
- 5172-077
- 2014-003836-38 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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