Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) With or Without Ribavirin for Participants With Hepatitis C Genotype 1, 4, or 6 Infections Who Have Failed Prior Treatment With Pegylated Interferon + Ribavirin (MK-5172-068)

NCT02105701 | Completed Phase 3 Results

• 2 other identifiers: 5172-0682014-000824-12
• Study Type: interventional
• Target: 420
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) with or without ribavirin (RBV) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infections who have failed prior therapy with pegylated interferon and RBV. The primary study hypothesis is that in at least one of the study arms, the percentage of participants achieving sustained viral response 12 weeks after the end of all study treatment (SVR12) will be superior to 58%.

Conditions

Hepatitis C Infection

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12)

  HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.

  12 weeks after the end of all study treatment (up to 28 weeks)

• Number of Participants Experiencing Adverse Events (AE)

  An AE 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.

  Up to 18 weeks

• Number of Participants Discontinuing Study Treatment Due to an AE

  An AE 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.

  Up to 16 weeks

Secondary Outcomes (1)

• Percentage of Participants Achieving Undetectable HCV RNA 24 Weeks After the End of All Treatment (SVR24)

  24 weeks after the end of all study treatment (up to 40 weeks)

Study Arms (4)

Grazoprevir + Elbasvir 12 weeks

EXPERIMENTAL

Participants receive grazoprevir 100 mg/elbasvir 50 mg fixed-dose combination (FDC) tablets once daily (q.d.) by mouth for 12 weeks.

Drug: Grazoprevir + Elbasvir

Grazoprevir + Elbasvir + RBV 12 weeks

EXPERIMENTAL

Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules twice daily (b.i.d.) by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.

Drug: Grazoprevir + Elbasvir; Drug: Ribavirin

Grazoprevir + Elbasvir 16 weeks

EXPERIMENTAL

Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.

Drug: Grazoprevir + Elbasvir

Grazoprevir + Elbasvir + RBV 16 weeks

EXPERIMENTAL

Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.

Drug: Grazoprevir + Elbasvir; Drug: Ribavirin

Interventions

Grazoprevir + Elbasvir DRUG

FDC tablet containing grazoprevir 100 mg and elbasvir 50 mg.

Also known as: MK-5172A

Grazoprevir + Elbasvir + RBV 12 weeks; Grazoprevir + Elbasvir + RBV 16 weeks; Grazoprevir + Elbasvir 12 weeks; Grazoprevir + Elbasvir 16 weeks

Ribavirin DRUG

200 mg capsule

Also known as: Rebetol®

Grazoprevir + Elbasvir + RBV 12 weeks; Grazoprevir + Elbasvir + RBV 16 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, GT4, or GT6 with no evidence of non-typable or mixed genotype infection (positive for anti-HCV antibody, HCV ribonucleic acid \[RNA\], or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
• Cirrhosis defined as liver biopsy showing METAVIR F4; or Fibroscan showing result \>12.5 kilopascals (kPa); or FibroSure® (Fibrotest®) score of \>0.75 and an aspartate aminotransferase (AST):platelet ratio index (APRI) of \>2
• Absence of cirrhosis defined as liver biopsy showing absence of cirrhosis; or Fibroscan result of ≤ 12.5 kPa; or Fibrosure® (Fibrotest®) score of ≤ 0.48 and APRI ≤ 1
• Previous HCV treatment status of peginterferon/RBV Null responder; or peginterferon/RBV Partial responder; or peginterferon/RBV Treatment Relapse
• For human immunodeficiency virus (HIV) co-infected participants: documented HIV-1 infection; currently naïve to treatment with any antiretroviral therapy (ART) and have no plans to initiate ART treatment while participating in this study; or be on HIV ART for at least 8 weeks prior to study entry (dual nucleoside reverse transcriptase inhibitor \[NRTI\] backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) (no changes in HIV regimen allowed within 4 weeks of randomization); cluster of differentiation 4 (CD4)+ T-cell count \>200 cells/mm\^3 at screening; documented undetectable plasma HIV-1 RNA at least 8 weeks prior to screening; participants not on ART, HIV RNA must be \<50,000 copies/mL; must have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance
• 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; a male participant who is not (or whose partner is not) of reproductive potential is eligible without requiring the use of contraception

You may not qualify if:

• Evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
• For participants with cirrhosis, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score \>6, must be excluded
• Co-infected with hepatitis B virus
• Has had previous direct-acting antiviral treatment
• History of malignancy \<=5 years prior except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy
• Has cirrhosis and liver imaging showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
• Taking or plans to take any HIV therapy that includes a ritonavir-boosted or unboosted protease inhibitor, efavirenz or etravirine
• 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
• Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; or is a male whose female partner(s) is/are pregnant
• History of organ transplant (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 corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• Kwo P, Gane EJ, Peng CY, Pearlman B, Vierling JM, Serfaty L, Buti M, Shafran S, Stryszak P, Lin L, Gress J, Black S, Dutko FJ, Robertson M, Wahl J, Lupinacci L, Barr E, Haber B. Effectiveness of Elbasvir and Grazoprevir Combination, With or Without Ribavirin, for Treatment-Experienced Patients With Chronic Hepatitis C Infection. Gastroenterology. 2017 Jan;152(1):164-175.e4. doi: 10.1053/j.gastro.2016.09.045. Epub 2016 Oct 5.

  PMID: 27720838 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

• Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.

  PMID: 29404492 DERIVED

• 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

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; 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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 7, 2014
• Study Start: June 5, 2014
• Primary Completion: March 24, 2015
• Study Completion: June 19, 2015
• Last Updated: February 5, 2021
• Results First Posted: March 4, 2016

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share