Efficacy and Safety of Combination Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) in Genotype 2 Hepatitis C Infection (MK-5172-047)

NCT01932762 | Completed Phase 2 Results

• 2 other identifiers: 5172-0472013-002169-21
• Study Type: interventional
• Target: 98
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-site, open-label trial evaluating the safety and efficacy of 100 mg of grazoprevir (MK-5172) used in combination with or without 50 mg of elbasvir (MK-8742) and/or ribavirin (RBV) in treating non-cirrhotic treatment-naïve participants with chronic genotype (GT) 2, 4, 5, and 6 hepatitis C infection. In Part A there is no randomization or stratification; all GT2 participants will be assigned to arm A1. In Part B, all GT2 participants will be assigned to Arm B1 and all participants with GT4, GT5 and GT6 will be randomized in a 1:1 ratio to either Arm 3 or Arm 4 with stratification by genotype.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (2)

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

  SVR12 was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) \<25 IU/mL, either target detected but unquantifiable (TD\[u\]) or target not detected (TND), at 12 weeks after the end of all study therapy. The percentage of participants with SVR12 and accompanying 95% confidence intervals (CIs) were reported for each treatment arm in the Per-Protocol (PP) Population.

  12 weeks after end of all therapy (Study Week 24)

• Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AEs, Drug-Related SAEs, or Discontinuation of Study Treatment Due to AE During the Treatment Period and First 14 Follow-up Days

  AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The investigator determined the relationship of the AE to the treatment as unrelated or possibly, probably, or definitely related.

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

Secondary Outcomes (5)

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

  From TW1 until first achievement of undetectable HCV RNA (up to 12 weeks)

• Percentage of Participants Achieving Undetectable HCV RNA During Treatment By Timepoint

  From TW 2 through TW 12 (up to 12 weeks)

• Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment By Timepoint

  From TW 2 through TW 12 (up to 12 weeks)

• Percentage of Participants Achieving SVR4

  4 weeks after end of all therapy (Study Week 16)

• Percentage of Participants Achieving SVR24

  24 weeks after end of all therapy (Study Week 36)

Study Arms (4)

GT2: Grazoprevir + Elbasvir + RBV (Arm A1)

EXPERIMENTAL

During Part A of the study, GT2 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.

Drug: Grazoprevir; Drug: Elbasvir; Drug: Ribavirin

GT2: Grazoprevir + RBV (Arm B1)

EXPERIMENTAL

During Part B of the study, GT2 participants will receive 100 mg grazoprevir + standard weight-based dosing of RBV for 12 weeks.

Drug: Grazoprevir; Drug: Ribavirin

GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)

EXPERIMENTAL

During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.

Drug: Grazoprevir; Drug: Elbasvir; Drug: Ribavirin

GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)

EXPERIMENTAL

During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir for 12 weeks.

Drug: Grazoprevir; Drug: Elbasvir

Interventions

Grazoprevir DRUG

100 mg every day (QD) orally

Also known as: MK-5172

GT 4,5,6: Grazoprevir + Elbasvir (Arm B3); GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2); GT2: Grazoprevir + Elbasvir + RBV (Arm A1); GT2: Grazoprevir + RBV (Arm B1)

Elbasvir DRUG

50 mg QD orally

Also known as: MK-8742

GT 4,5,6: Grazoprevir + Elbasvir (Arm B3); GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2); GT2: Grazoprevir + Elbasvir + RBV (Arm A1)

Ribavirin DRUG

Administered twice daily (BID) orally at a total daily dose of 800 mg to 1400 mg based on participant's weight on Day 1

Also known as: Rebetol™

GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2); GT2: Grazoprevir + Elbasvir + RBV (Arm A1); GT2: Grazoprevir + RBV (Arm B1)

Eligibility Criteria

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

You may qualify if:

• Parts A and B: -Body weight ≥50 kg (111 lbs) and ≤ 125 kg (275 lbs) -Has absence of cirrhosis -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 female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential).
• Part A only: -Has chronic HCV GT2 infection Part B only: -Has chronic HCV GT2, GT4, GT5, or GT6 infection

You may not qualify if:

• Parts A and B:
• Is not treatment naïve (participant has had previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV) -Is determined to be coinfected with hepatitis B virus (HBsAg positive) or HIV -Has evidence of, or is under evaluation for, hepatocellular carcinoma (HCC) -Has a clinical diagnosis of substance abuse including the following specified drugs within specified timeframes: Alcohol, intravenous drugs, inhalational, psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs (within 1 year of the screening visit), is receiving opiate agonist substitution therapy (within 1 year of screening visit), or excessive historic marijuana use -Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years -Female participant who is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment, or male participant who is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using a two methods of birth control throughout treatment and after the completion of all treatment -Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. -Has uncontrolled diabetes (documented HbA1c \>8.5%)
• Part A only:
• Has non GT2 HCV infection
• Part B only:
• Has HCV infection with a genotype other than GT2, GT4, GT5 or GT6

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Brown A, Hezode C, Zuckerman E, Foster GR, Zekry A, Roberts SK, Lahser F, Durkan C, Badshah C, Zhang B, Robertson M, Wahl J, Barr E, Haber B; C-SCAPE Study Investigators. Efficacy and safety of 12 weeks of elbasvir +/- grazoprevir +/- ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C-SCAPE study. J Viral Hepat. 2018 May;25(5):457-464. doi: 10.1111/jvh.12801. Epub 2018 Mar 14.

  PMID: 29152828 RESULT

• 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.

  PMID: 29461687 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

grazoprevir; elbasvir; 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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: August 30, 2013
• Study Start: October 1, 2013
• Primary Completion: December 4, 2014
• Study Completion: December 4, 2014
• Last Updated: February 4, 2021
• Results First Posted: March 4, 2016

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share