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

Hepatitis C Clinical Trial

Official title:

A Phase III Randomized Multinational Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT 1, GT 4 and GT 6 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02251990
• Other study ID #: 5172-067
• Status: Completed
• Phase: Phase 3
• Start date: January 28, 2015
• Est. completion date: April 10, 2017

Study information

• Verified date: January 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to the historical reference rate of 73%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 489
• Est. completion date: April 10, 2017
• Est. primary completion date: September 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

Drug:
• Grazoprevir/Elbasvir
FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks.
• Placebo
Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

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/gr — View Citation

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. 2018 Oct 12. doi: 10.1111/jgh.14509. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)	Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA	4 weeks after end of all therapy (Study Week 16)
Primary	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 (	12 weeks after end of all therapy (Study Week 24)
Primary	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)
Primary	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	Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)	Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA	24 weeks after end of all therapy (Study Week 36)