Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067)

NCT02251990 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 5172-067
• Study Type: interventional
• Target: 489
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, parallel-group, placebo-controlled, multi-site, multinational, double-blind followed by open label period, Phase 3 trial of 100 mg of grazoprevir (MK-5172) in combination with 50 mg of elbasvir (MK-8742) (grazoprevir/elbasvir fixed-dose combination \[FDC\]) in treatment-naïve (TN) participants with chronic hepatitis C virus (HCV), genotype (GT) 1, 4 or 6 infection. The primary hypothesis is that the percentage of participants receiving grazoprevir/elbasvir FDC in the Immediate Treatment Group (ITG) achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to the historical reference rate of 73%.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

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

  Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (\<LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.

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

• Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.

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

• Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.

  DB Treatment period (up to 12 weeks)

Secondary Outcomes (1)

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

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

Other Outcomes (1)

• Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)

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

Study Arms (2)

Immediate Treatment Group (ITG): Grazoprevir/Elbasvir

EXPERIMENTAL

Participants receive a grazoprevir/elbasvir FDC tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and are followed-up for 24 weeks to Week 36.

Drug: Grazoprevir/Elbasvir

Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir

PLACEBO COMPARATOR

Participants receive a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants receive open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants are then followed-up for 24 weeks to Week 52.

Drug: Placebo

Interventions

Grazoprevir/Elbasvir DRUG

FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks.

Also known as: MK-5172A

Immediate Treatment Group (ITG): Grazoprevir/Elbasvir

Placebo DRUG

Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks.

Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir

Eligibility Criteria

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

You may qualify if:

• Has documented chronic HCV GT1, GT4, or GT6 (with no evidence of non-typeable or mixed genotype) infection
• Meets clinical criteria for presence or absence of cirrhosis based on liver disease staging assessment
• Is abstinent or uses acceptable method(s) of contraception

You may not qualify if:

• Has evidence of decompensated liver disease
• Is coinfected with hepatitis B virus or human immunodeficiency virus (HIV)
• Shows evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
• Has a clinically-relevant drug or alcohol abuse within 12 months of screening
• Is pregnant or breast-feeding
• Has any condition or abnormality that might confound the results of the trial or pose an additional risk to the participant

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (5)

• Wei L, Jia JD, Wang FS, Niu JQ, Zhao XM, Mu S, Liang LW, Wang Z, Hwang P, Robertson MN, Ingravallo P, Asante-Appiah E, Wei B, Evans B, Hanna GJ, Talwani R, Duan ZP, Zhdanov K, Cheng PN, Tanwandee T, Nguyen VK, Heo J, Isakov V, George J; C-CORAL Investigators. Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study. J Gastroenterol Hepatol. 2019 Jan;34(1):12-21. doi: 10.1111/jgh.14509. Epub 2018 Dec 9.

  PMID: 30311701 BACKGROUND

• George J, Burnevich E, Sheen IS, Heo J, Kinh NV, Tanwandee T, Cheng PN, Kim DY, Tak WY, Kizhlo S, Zhdanov K, Isakov V, Liang L, Lindore P, Ginanni J, Nguyen BY, Wahl J, Barr E, Robertson M, Ingravallo P, Talwani R; C-CORAL Study Investigators. Elbasvir/grazoprevir in Asia-Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection. Hepatol Commun. 2018 Apr 4;2(5):595-606. doi: 10.1002/hep4.1177. eCollection 2018 May.

  PMID: 29761174 RESULT

• Dalgard O, Litwin AH, Shibolet O, Grebely J, Nahass R, Altice FL, Conway B, Gane EJ, Luetkemeyer AF, Peng CY, Iser D, Gendrano IN, Kelly MM, Haber BA, Platt H, Puenpatom A; CO-STAR Investigators. Health-related quality of life in people receiving opioid agonist treatment and treatment for hepatitis C virus infection. J Addict Dis. 2023 Jul-Sep;41(3):213-224. doi: 10.1080/10550887.2022.2088978. Epub 2022 Aug 3.

  PMID: 35920743 DERIVED

• Wei L, Jia JD, Duan ZP, Wang FS, Niu JQ, Xie W, Huang WX, Zhang MX, Huang Y, Wang MR, Wu SM, Zhao YR, Jia ZS, Zhao XM, Mu SM, Liang LW, Wang Z, Puenpatom A, Hwang P, Robertson MN, Ingravallo P, Asante-Appiah E, Wei B, Evans B, Hanna GJ, Talwani R. Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial. JGH Open. 2020 Jul 15;4(6):1065-1073. doi: 10.1002/jgh3.12387. eCollection 2020 Dec.

  PMID: 33319038 DERIVED

• 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

elbasvir-grazoprevir drug combination

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

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: September 29, 2014
• Study Start: January 28, 2015
• Primary Completion: September 27, 2016
• Study Completion: April 10, 2017
• Last Updated: January 30, 2019
• Results First Posted: October 17, 2017

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share