Clinical trial NCT03143998: Efficacy and Safety of Elbasvir/Grazoprevir in Brazilian Participants With Chronic Hepatitis C Virus (HCV) Genotype 1 Infection With Advanced Fibrosis (F3 and F4)
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-05-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of participants achieving sustained virologic response (SVR) 12 weeks after the end of all study therapy (SVR12)
timeFrame: Week 24 (12 weeks after completing study therapy)
measure: Percentage of participants experiencing an adverse event (AE)
timeFrame: Up to 14 weeks
measure: Percentage of participants withdrawing from study therapy due to an AE
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Percentage of participants achieving SVR 24 weeks after the end of all study therapy (SVR24)
timeFrame: Week 36 (24 weeks after completing study therapy)
measure: Emergence of viral resistance-associated variants (RAVs)
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: