Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-003)

NCT01353911 | Completed Phase 2 Results DMC

• 2 other identifiers: 5172-0032011-000759-18
• Study Type: interventional
• Target: 368
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) in treatment-naïve (TN) participants with chronic hepatitis C.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Complete Early Viral Response (cEVR)

  Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected \[TND\]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.

  After 12 weeks of treatment with grazoprevir/boceprevir

• Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days

  An AE was 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. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

  Treatment period plus the first 14 days of follow-up (up to 50 weeks)

• Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days

  An AE was 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. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

  Treatment period plus the first 14 days of follow-up (up to 50 weeks)

Secondary Outcomes (5)

• Median Time to First Achievement of Undetectable HCV RNA During Treatment

  From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)

• Percentage of Participants Achieving Rapid Viral Response (RVR)

  After 4 weeks of treatment with grazoprevir/boceprevir

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

  12 weeks after the end of all treatment (up to 60 weeks)

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)

  24 weeks after the end of all treatment (up to 72 weeks)

• Percentage of Participants Achieving Undetectable HCV RNA at Week 72

  Week 72

Study Arms (8)

Grazoprevir 100 mg

EXPERIMENTAL

TN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Grazoprevir 200 mg

EXPERIMENTAL

TN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Grazoprevir 400 mg

EXPERIMENTAL

TN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Grazoprevir 800 mg

EXPERIMENTAL

TN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Boceprevir 800 mg

ACTIVE COMPARATOR

TN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Boceprevir; Drug: Placebo for Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Grazoprevir 400 mg/100 mg

EXPERIMENTAL

As the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.

Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Grazoprevir 800 mg/100 mg

EXPERIMENTAL

As the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.

Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

OL Grazoprevir 100 mg

EXPERIMENTAL

TN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

Interventions

Grazoprevir DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Grazoprevir 100 mg; Grazoprevir 200 mg; Grazoprevir 400 mg; Grazoprevir 400 mg/100 mg; Grazoprevir 800 mg; Grazoprevir 800 mg/100 mg; OL Grazoprevir 100 mg

Boceprevir DRUG

Four 200 mg capsules orally three times daily.

Also known as: Victrelis

Boceprevir 800 mg

Placebo for Grazoprevir DRUG

Orally once daily in AM.

Boceprevir 800 mg

Placebo for Boceprevir DRUG

Four capsules orally three times daily.

Grazoprevir 100 mg; Grazoprevir 200 mg; Grazoprevir 400 mg; Grazoprevir 800 mg

Peg-interferon alfa-2b DRUG

1.5 μg/kg/week subcutaneous injection.

Also known as: PegIntron, Peg-IFN alfa-2b

Boceprevir 800 mg; Grazoprevir 100 mg; Grazoprevir 200 mg; Grazoprevir 400 mg; Grazoprevir 400 mg/100 mg; Grazoprevir 800 mg; Grazoprevir 800 mg/100 mg; OL Grazoprevir 100 mg

Ribavirin DRUG

300 mg to 700 mg orally twice daily.

Also known as: Rebetol

Boceprevir 800 mg; Grazoprevir 100 mg; Grazoprevir 200 mg; Grazoprevir 400 mg; Grazoprevir 400 mg/100 mg; Grazoprevir 800 mg; Grazoprevir 800 mg/100 mg; OL Grazoprevir 100 mg

Eligibility Criteria

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

You may qualify if:

• Has previously documented chronic hepatitis C genotype 1 (CHC GT 1) infection
• Has hepatitis C virus (HCV) ribonucleic acid (RNA value) ≥10,000 IU/mL
• Body weight ≥40 kg (88 lbs) and ≤125 kg (275 lbs)
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs and symptoms of decompensated liver disease
• Had a liver biopsy within 3 years of screening or between screening and Day 1 with histology consistent with CHC and no evidence of cirrhosis or hepatocellular carcinoma or no other cause for chronic liver disease (for participants with compensated cirrhosis, any liver biopsy demonstrating cirrhosis regardless of length of time since biopsy)
• Female of childbearing potential or a male with female sexual partner who is of childbearing potential agrees 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 participants with compensated cirrhosis, evidence of cirrhosis without evidence of hepatocellular carcinoma (confirmed by ultrasound within 4 weeks prior)

You may not qualify if:

• Is pregnant, breastfeeding, or plans to become pregnant or donate eggs
• Is human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
• Has received prior approved or investigational treatment for hepatitis C
• Has evidence of hepatocellular carcinoma or is under evaluation for hepatocellular carcinoma
• For participants with compensated cirrhosis: alphafetoprotein level of ≥100 ng/mL
• Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
• Has evidence or history of chronic hepatitis not caused by HCV
• Is diabetic and/or hypertensive with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality
• Has any known medical condition that could interfere with participation in and completion of the study
• Pre-existing psychiatric condition including but not limited to moderate or severe depression, suicidal or homicidal ideation or attempt, schizophrenia, psychosis, bipolar disorder, post traumatic stress disorder, or mania
• Is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
• Member or family member of study staff

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Manns MP, Vierling JM, Bacon BR, Bruno S, Shibolet O, Baruch Y, Marcellin P, Caro L, Howe AY, Fandozzi C, Gress J, Gilbert CL, Shaw PM, Cooreman MP, Robertson MN, Hwang P, Dutko FJ, Wahl J, Mobashery N. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology. 2014 Aug;147(2):366-76.e6. doi: 10.1053/j.gastro.2014.04.006. Epub 2014 Apr 12.

  PMID: 24727022 RESULT

• Howe AY, Black S, Curry S, Ludmerer SW, Liu R, Barnard RJ, Newhard W, Hwang PM, Nickle D, Gilbert C, Caro L, DiNubile MJ, Mobashery N. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis. 2014 Dec 15;59(12):1657-65. doi: 10.1093/cid/ciu696. Epub 2014 Sep 28.

  PMID: 25266289 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

grazoprevir; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2011
• First Posted: May 16, 2011
• Study Start: June 27, 2011
• Primary Completion: January 20, 2013
• Study Completion: March 10, 2015
• Last Updated: May 22, 2024
• Results First Posted: March 2, 2016

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share