A Study of Different Durations of Treatment With Grazoprevir (MK-5172) in Combination With Ribavirin in Participants With Chronic Hepatitis C (MK-5172-039)

NCT01716156 | Completed Phase 2 Results

• 2 other identifiers: 5172-0392012-003340-72
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare two different durations of treatment with grazoprevir (MK-5172) in combination with ribavirin (RBV) in treatment-naïve non-cirrhotic interferon-eligible interleukin 28b CC (IL28B CC) genotype participants with genotype 1 (GT1)-positive chronic hepatitis C (CHC). Participants will be randomized to receive 12 or 24 weeks of combination therapy.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)

  SVR12 was defined as HCV RNA \<25 IU/mL 12 weeks after the end of all study therapy. HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.

  Up to Week 36

• Percentage of Participants Experiencing at Least One Adverse Event (AE) on Study

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.

  Fourteen days following last dose of study drug (up to 26 weeks)

• Percentage of Participants Discontinuing Study Therapy Due to an AE

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.

  Up to 24 weeks

Secondary Outcomes (5)

• Time to Achievement of First Undetectable HCV RNA

  Up to Week 24

• Percentage of Participants With Undetectable HCV RNA by Time Point

  From Week 2 through end of treatment (up to 24 weeks)

• Percentage of Participants With HCV RNA <25 IU/mL by Time Point

  From Week 2 through end of treatment (up to 24 weeks)

• Percentage of Participants With Sustained Virologic Response 4 Weeks After Ending Study Therapy (SVR4)

  Up to Week 28

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR 24)

  Up to Week 48

Study Arms (2)

Grazoprevir 100 mg + RBV 12 Weeks

EXPERIMENTAL

Grazoprevir 100 mg tablet once per day by mouth for 12 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 12 weeks. Participants with detectable HCV RNA at TW4 received an additional 12 weeks of study therapy for a total of 24 weeks of treatment.

Drug: Grazoprevir; Drug: Ribavirin

Grazoprevir 100 mg + RBV 24 Weeks

EXPERIMENTAL

Grazoprevir 100 mg tablet once per day by mouth for 24 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 24 weeks.

Drug: Grazoprevir; Drug: Ribavirin

Interventions

Grazoprevir DRUG

Grazoprevir, tablet, orally, 100 mg, once per day for 12 or 24 weeks, depending on Arm assignment

Grazoprevir 100 mg + RBV 12 Weeks; Grazoprevir 100 mg + RBV 24 Weeks

Ribavirin DRUG

Ribavirin capsules, orally, twice per day, at a total daily dose from 800 to 1400 mg based on participant weight

Also known as: Rebetol™, RBV

Grazoprevir 100 mg + RBV 12 Weeks; Grazoprevir 100 mg + RBV 24 Weeks

Eligibility Criteria

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

You may qualify if:

• Chronic, compensated HCV GT 1 hepatitis C
• IL28B CC genotype
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
• No evidence of cirrhosis and hepatocellular carcinoma by biopsy or noninvasive tests (FibroScan and/or FibroTest)
• Agree to use two 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 (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential)

You may not qualify if:

• Non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype
• Previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV
• Human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
• 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 study
• Diabetes and/or hypertension with clinically significant ocular examination findings
• Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
• Clinical diagnosis of substance abuse
• Current or history of seizure disorder, stroke, or transient ischemic attack
• Immunologically-mediated disease
• Chronic pulmonary disease
• Clinically significant cardiac abnormalities/dysfunction
• Active clinical gout within the last year
• Hemoglobinopathy or myelodysplastic syndromes
• History of organ transplants

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Gane E, Ben Ari Z, Mollison L, Zuckerman E, Bruck R, Baruch Y, Howe AY, Wahl J, Bhanja S, Hwang P, Zhao Y, Robertson MN. Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1 infection. J Viral Hepat. 2016 Oct;23(10):789-97. doi: 10.1111/jvh.12552. Epub 2016 Jun 12.

  PMID: 27291249 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

grazoprevir; Ribavirin

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)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 29, 2012
• Study Start: January 18, 2013
• Primary Completion: December 9, 2013
• Study Completion: March 12, 2014
• Last Updated: September 24, 2018
• Results First Posted: March 4, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share