Efficacy and Safety of Elbasvir/Grazoprevir in Brazilian Participants With Chronic Hepatitis C Virus (HCV) Genotype 1 Infection With Advanced Fibrosis (F3 and F4)

Hepatitis C Clinical Trial

Official title:

A Multi-Site, Open-Label, Trial of the Efficacy and Safety of Fixed-dose Elbasvir/Grazoprevir (EBR/GZR) in Brazilian Patients With Chronic Hepatitis C Virus (HCV) Genotype 1 Infection With Advanced Fibrosis (F3 and F4)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03143998
• Other study ID #: 5172-089
• Status: Withdrawn
• Phase: Phase 4
• First received: May 4, 2017
• Last updated: November 7, 2017
• Start date: February 12, 2018
• Est. completion date: January 12, 2019

Study information

• Verified date: November 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a non-randomized, open-label study of a fixed dose combination (FDC) of elbasvir (50 mg) and grazoprevir (100 mg) (EBR/GZR or MK-5172A) in participants with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection with advanced fibrosis with and without human immunodeficiency virus (HIV) co-infection. All participants will be either HCV treatment naïve (TN) or treatment experienced (TE).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 12, 2019
• Est. primary completion date: January 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult (= 18 years of age) male and female participants with chronic HCV GT1 infection who reside in Brazil

• HCV RNA (= 10,000 IU/mL in peripheral blood) at the time of screening

• Has documented chronic HCV GT1 (1a; 1b) infection (with no evidence of non-typeable or mixed genotype) infection.

• positive for anti HCV antibody, HCV RNA, or HCV GT1 at least 6 months before screening, or

• positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic hepatitis C (CHC) disease, such as the presence of fibrosis)

• Is otherwise healthy as determined by the medical history, physical examination, and clinical laboratory measurements at the time of screening

• Has a history of advanced fibrosis (F3 or F4) as follows:

• F4: FibroSure®/APRI + FibroTest®

• Liver biopsy result of METAVIR stage 3 or 4 fibrosis (or its grading system equivalency to advanced fibrosis)

• FibroScan® result > 9.5 kPa (F3 or F4)

• Has liver imaging within 6 months of Day 1 (start of treatment) with no evidence of hepatocellular carcinoma (HCC)

• Is TN or TE

• Is a male, is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant from Day 1 (start of treatment) through 14 days after the last dose of study drug (or longer if dictated by local regulations)

• For HIV-infected participants, has HIV-1 infection documented prior to screening, and is either not currently on antiretroviral therapy (ART) and has no plans to initiate ART or has well-controlled HIV on ART as per study criteria

Exclusion Criteria:

• Has prior treatment with direct acting antiviral (DAA) therapy with the exception of boceprevir, telaprevir, and simeprevir

• Has evidence of decompensated liver disease as manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease

• Is classified as Child-Pugh B or C or has a Child-Pugh-Turcotte score > 6

• Is hepatitis B surface antigen (HBsAg) positive at screening

• Is under evaluation for HCC or other active or suspected malignancy

• Is currently participating or has participated in a study with an investigational compound within 1 year of signing informed consent and is not willing to refrain from participating in another such study during the course of this study

• Has clinically-relevant drug or alcohol abuse within 12 months of screening

• Is a female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from Day 1 (start of treatment) through 14 days after the last dose of study drug or longer if dictated by local regulations; or is a male participant who is expecting to donate sperm from Day 1 (start of treatment) through 14 days after the last dose of study drug or longer if dictated by local regulations

• Has any clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with treatment, assessment or compliance with the protocol or any medical/surgical conditions that may result in a need for hospitalization during the period of the study; or is currently under evaluation for a potentially clinically-significant illness (other than HCV)

Related Conditions & MeSH terms

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

Intervention

Drug:
• MK-5172A
A single FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants achieving sustained virologic response (SVR) 12 weeks after the end of all study therapy (SVR12)	SVR12 will be declared when a participant has HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks after the end of all study therapy. Levels of HCV RNA will be determined with the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0, which has a LLoQ of 15 IU/mL.	Week 24 (12 weeks after completing study therapy)
Primary	Percentage of participants experiencing an adverse event (AE)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 14 weeks
Primary	Percentage of participants withdrawing from study therapy due to an AE	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 12 weeks
Secondary	Percentage of participants achieving SVR 24 weeks after the end of all study therapy (SVR24)	SVR24 will be declared when a participant has HCV RNA < LLOQ 24 weeks after the end of all study therapy. Levels of HCV RNA will be determined with the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0, which has a LLoQ of 15 IU/mL.	Week 36 (24 weeks after completing study therapy)
Secondary	Emergence of viral resistance-associated variants (RAVs)	The RAVs resistant to EBR or GZR, including the association of baseline RAVs with treatment outcomes (SVR12 and SVR24) and the emergence of RAVs in participants who fail to achieve SVR will be determined.	Up to 12 weeks