Clinical trial NCT02601573: Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic Hepatitis C Virus (HCV) Genotype 3 (GT3) Infection (MK-5172-083)
Official title: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic HCV GT3 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-11-10
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.


Eligibility criteria: Inclusion Criteria:

* has HCV RNA (\>= 10,000 IU/mL in peripheral blood) at screening
* has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection)
* has compensated cirrhosis of the liver
* has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC)
* is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin)
* is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements
* has compensated cirrhosis of the liver
* is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin)
* is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations)

Exclusion Criteria:

* has previously received one or more doses of a direct-acting antiviral (DAA)
* has evidence of decompensated liver disease
* is coinfected with hepatitis B (hepatitis B surface antigen \[HBsAg\] positive)
* has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy
* is currently or has participated (within past 30 days) in a study with an investigational compound
* has clinically-relevant drug or alcohol abuse within the past 12 months of screening
* is a female and is pregnant or breast-feeding
* is a male whose female partner is/are pregnant
* has any of the following:
* organ transplants
* poor venous access
* history of gastric surgery or malabsorption disorder
* current or history of clinically significant cardiac abnormalities or dysfunction
* chronic pulmonary disease
* hemoglobinopathy
* history of hospitalization within 3 months prior to enrollment
* medical or surgical condition that may result in need for hospitalization during the course of the study
* any condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppresant drugs during the course of the study
* any condition, prestudy laboratory or ECG abnormality, or history of any illness, which could confound results of the study or pose additional risks in administering study drugs in the opinion of the investigator
* has a life-threatening serious AE (SAE) during the screening period
* has evidence of history of chronic hepatitis not caused by HCV

Primary outcomes:
measure: Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy)
timeFrame: Up to Week 28
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 18 weeks (up to 2 weeks after completion of study treatment)
measure: Percentage of Participants Discontinuing From Study Therapy Due to an AE
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy)
timeFrame: Up to Week 40
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Foster GR, Agarwal K, Cramp ME, Moreea S, Barclay S, Collier J, Brown AS, Ryder SD, Ustianowski A, Forton DM, Fox R, Gordon F, Rosenberg WM, Mutimer DJ, Du J, Gilbert CL, Asante-Appiah E, Wahl J, Robertson MN, Barr E, Haber B. Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial. Hepatology. 2018 Jun;67(6):2113-2126. doi: 10.1002/hep.29852. Epub 2018 Apr 19.