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)

NCT02105454 | Completed Phase 2 Results

• 2 other identifiers: 5172-0482013-004213-41
• Study Type: interventional
• Target: 79
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study, participants with hepatitis C virus (HCV) genotype 1 (GT1) who failed prior direct-acting antiviral (DAA) therapy will receive Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) to evaluate sustained virologic response (SVR) using this drug combination.

Conditions

Hepatitis C Virus

Outcome Measures

Primary Outcomes (3)

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

  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.

  Up to 24 weeks

• Percentage of Participants Experiencing Adverse Events

  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.

  Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)

• Percentage of Participants Discontinuing Study Drug Due to an Adverse Event

  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.

  Up to 12 weeks

Secondary Outcomes (1)

• Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy

  Up to 24 weeks

Study Arms (1)

GZR 100 mg + EBR 50 mg + RBV for 12 weeks

EXPERIMENTAL

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); Drug: Elbasvir (EBR); Drug: Ribavirin (RBV)

Interventions

Grazoprevir (GZR) DRUG

100 mg oral tablet (total daily dose)

GZR 100 mg + EBR 50 mg + RBV for 12 weeks

Elbasvir (EBR) DRUG

10 mg oral capsule (total daily dose = 5 capsules)

GZR 100 mg + EBR 50 mg + RBV for 12 weeks

Ribavirin (RBV) DRUG

200 mg oral capsule (total daily dose = 4-7 capsules)

GZR 100 mg + EBR 50 mg + RBV for 12 weeks

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• 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.

  PMID: 25895428 BACKGROUND

• Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.

  PMID: 28193518 DERIVED

• 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.

  PMID: 26371152 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 7, 2014
• Study Start: May 23, 2014
• Primary Completion: May 4, 2015
• Study Completion: May 4, 2015
• Last Updated: September 24, 2018
• Results First Posted: March 4, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share