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) - Full Text View

Condition	Intervention	Phase
Hepatitis C Virus	Drug: Grazoprevir (GZR) Drug: Elbasvir (EBR) Drug: Ribavirin (RBV)	Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	A Phase II Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 + MK-8742 + Ribavirin (R) in Subjects With Chronic Hepatitis C Virus Infection Who Failed Prior Direct Acting Antiviral Therapy

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12) [ Time Frame: 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.
Percentage of Participants Experiencing Adverse Events [ Time Frame: 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.
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event [ Time Frame: 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.

Secondary Outcome Measures:

Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy [ Time Frame: 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.


Enrollment:	79
Study Start Date:	May 2014
Study Completion Date:	May 2015
Primary Completion Date:	May 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GZR 100 mg + EBR 50 mg + RBV for 12 weeks Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks	Drug: Grazoprevir (GZR) 100 mg oral tablet (total daily dose) Drug: Elbasvir (EBR) 10 mg oral capsule (total daily dose = 5 capsules) Drug: Ribavirin (RBV) 200 mg oral capsule (total daily dose = 4-7 capsules)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Documented chronic HCV GT1 infection (with no evidence of non-typable or mixed genotype)
Absence of cirrhosis, or cirrhosis with these criteria: METAVIR F4, or Fibroscan with result >12.5 kPa, or FibroSure® (Fibrotest®) score of >0.75 + aspartate aminotransferase (AST): platelet ratio index (APRI) of >2- Prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir), pegylated interferon, and/or RBV
Participants of reproductive potential must agree to remain truly abstinent or use (or have their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion criteria:

Received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with pegylated interferon and/or RBV
Evidence of decompensated liver disease or cirrhosis
Co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
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 of screening
Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations
Male participant whose female partner (s) is/are pregnant
Organ transplants (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 administration of corticosteroids during the course of the trial
Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02105454

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information

Publications:

Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Buti M, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Forns X. 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. Clin Infect Dis. 2016 Jan 1;62(1):32-6. doi: 10.1093/cid/civ722. Epub 2015 Sep 14.


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT02105454 History of Changes
Other Study ID Numbers:	5172-048 2013-004213-41 ( EudraCT Number )
Study First Received:	April 2, 2014
Results First Received:	February 3, 2016
Last Updated:	March 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases	Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Ribavirin Antiviral Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Anti-Infective Agents

ClinicalTrials.gov processed this record on September 21, 2017