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)

Hepatitis C Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02105454
• Other study ID #: 5172-048
• Secondary ID: 2013-004213-41
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2014
• Est. completion date: May 4, 2015

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: May 4, 2015
• Est. primary completion date: May 4, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Grazoprevir (GZR)
100 mg oral tablet (total daily dose)
• Elbasvir (EBR)
10 mg oral capsule (total daily dose = 5 capsules)
• Ribavirin (RBV)
200 mg oral capsule (total daily dose = 4-7 capsules)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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	Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy	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.	Up to 24 weeks