Open-Label Efficacy and Safety Study of the Elbasvir/ Grazoprevir Fixed Dose Combination Patients With Chronic HCV GT1b

NCT03222167 | Unknown Phase 3

• 1 other identifier: ICID.HCV.0117
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label trial of Elbasvir/ Grazoprevir 50/100 mg fixed dose combination 12 week treatment aimed to evaluate SVR12 in treatment naïve patients with chronic hepatitis C (genotype 1b) infection, associated with of metabolic syndrome. The study to be conducted in conformance with Good Clinical Practices. A total of 60 subjects will be studied at 2 sites in the Republic of Kazakhstan. Males and Females treatment naïve patients with CHC genotype 1b infection associated with metabolic syndrome (MS), 18-70 years of age, with or without severe fibrosis / compensated cirrhosis will be enrolled. SVR 12 (primary endpoint) will be evaluated. Patients will be stratified by fibrosis stage and presence of metabolic syndrome components. Interim Analysis will be performed in order to estimate viral kinetics, applicability of SVR4 and durability of SVR12 by evaluation of virologic response at week 4 and 8 of treatment and follow-up at week 4 (SVR 4) and 24 will be performed - this will be a descriptive summary only without hypothesis testing. The main hypothesis is that 12-week therapy with MK-5172 in combination with MK-8742 for treatment-naïve patients with HCV genotype 1b with metabolic syndrome is not notably worse than the same course for treatment-naïve patients with HCV genotype 1b without metabolic syndrome.

Conditions

Chronic Hepatitis C Genotype 1B; Metabolic Syndrome; Fibrosis, Liver; Cirrhoses, Liver

Keywords

Elbasvir; Grazoprevir; SVR12; hepatitis C; metabolic syndrome

Outcome Measures

Primary Outcomes (1)

• SVR12 evaluation

  The main outcome is SVR12, defined as HCV RNA \< LLOQ (either TD\[u\] or TND)

  12 weeks after the end of all study therapy (treatment success).

Secondary Outcomes (1)

• Death/Lost

  24 weeks

Other Outcomes (1)

• HCV-RNA values

  24 weeks

Study Arms (1)

Elbasvir/ Grazoprevir

EXPERIMENTAL

Elbasvir/ Grazoprevir 50/100 mg fixed dose combination for 12 weeks treatment aimed to evaluate SVR12 in treatment naïve patients with chronic hepatitis C (genotype 1b) infection, associated with metabolic syndrome, with or without severe fibrosis / compensated cirrhosis.

Drug: Elbasvir/ Grazoprevir 50/100 mg fixed dose combination

Interventions

Elbasvir/ Grazoprevir 50/100 mg fixed dose combination DRUG

Enrolled patients will be treated by Elbasvir/ Grazoprevir 50/100 mg fixed dose combination during 12 week. Followed-up on week 24. SVR12 will be evaluated.

Elbasvir/ Grazoprevir

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be 18-70 years of age on a day of signing of informed consent.
• Have ≤40 kg/m2.
• Have HCV RNA ≥ 10,000 IU/mL at the time of screening.
• Have documented chronic HCV GT1b (with no evidence of non-typeable or mixed genotype) infection (positive for anti-HCV antibody, HCV RNA, or HCV GT1b at least 6 months before screening).
• Have liver disease staging assessment by means of liver biopsy performed within 12 calendar months prior to Day 1 of this study or Fibroscan performed within 6 calendar months prior to Day 1 of this study (cut-off of 12.5 kPa has a positive predictive value of 90% and a sensitivity of 95% for ≥F3).
• Be HIV and HBV negative.
• Be naïve to all anti-HCV treatment.
• Have provided written informed consent for the trial.
• Be diagnosed with metabolic syndrome (according to guidelines from the National Heart, Lung, and Blood Institute (NHLBI) and the American Heart Association (AHA)), i.e. have central obesity (defined as waist circumference in Asian males \>94 cm, in Caucasian males \>90 cm, in females \> 80 cm) combined with at least any of two of the following factors: (1) raised triglycerides ≥150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality; (2) reduced HDL cholesterol \< 40 mg/dL (1.03 mmol/L) in males or \< 50 mg/dL (1.29 mmol/L) in females or specific treatment for this lipid abnormality; (3) raised blood pressure - systolic BP ≥130 or diastolic BP ≥ 85 mm Hg or treatment of previously diagnosed hypertension; (4) raised fasting plasma glucose (FPG) ≥100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes.
• Reproductive potential patient agrees to avoid becoming pregnant or impregnating a partner until at least 6 months after the last dose of medication.

You may not qualify if:

• Is below 18 years of age.
• Has not signed Informed Consent Document.
• Has HCV genotype other than genotype 1b.
• Has BMI \> 40 kg/m2.
• Has history of clinically significant psychiatric disorder which in the opinion of the investigator, would interfere with the study procedures and compliance.
• Has received Peg/RBV, Telaprevir, or Boceprevir, or Sofosbuvir, or any other oral anti-HCV treatment/ combinations
• Has documented portal hypertension and hepatic decompensation (Child-Pugh B or C, esophageal varices, ascites, elevated bilirubin, jaundice, splenomegaly, hepatic encephalopathy, albumin below 3 g/dl; platelet count \< 75 000, INR\<1.7), history of liver decompensation.
• Has history of liver or other organ transplant.
• Has autoimmune hepatitis.
• Has ALT \> 10 x ULN.
• Is co-infected with hepatitis B virus (e.g., HBsAg positive) and HIV.
• Has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC (if liver imaging within 6 months of Day1 is not available, imaging is required during the screening).
• Has a clinically-relevant drug or alcohol abuse within 12 months of screening.
• Has decompensated DM with HbA1 \>12%.
• Has a medical/surgical condition that may result in a need for hospitalization during the period of the study.

Sponsors & Collaborators

• Institute Of Cardiology & Internal Diseases, Kazakhstan: lead
• Merck Sharp & Dohme LLC: collaborator
• Synergy Research Group: collaborator

Study Sites (1)

National Research Institute of Cardiology and Internal Medicine

Almaty, 050000, Kazakhstan

Location

MeSH Terms

Conditions

Metabolic Syndrome; Liver Cirrhosis; Hepatitis C

Interventions

elbasvir; grazoprevir

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 19, 2017
• Study Start: October 1, 2017
• Primary Completion: April 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 7, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

KA (1)