Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection

NCT ID: NCT02349048

Last Updated: 2017-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-05-31

Brief Summary

The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early stages of liver fibrosis or with cirrhosis.

Detailed Description

This is an open-label (participants and researchers are aware about the treatment participants are receiving), and multicenter (when more than 1 hospital or medical school team work on a medical research) study. The study will consist of a Screening Phase (6 weeks); an Open-label Treatment Phase (6 weeks for Arm A and 8 weeks for Arm B); and a Post-treatment Follow-up Phase (until 24 weeks after end of study treatment). Using a staggered approach, all eligible participants will be assigned to 1 of the 2 arms, according to their level of fibrosis. Arm A (consists of chronic HCV genotype 1 infected participants with early stages of liver fibrosis): participants will receive a combination therapy of SMV 150 milligram (mg), DCV 60 mg and SOF 400 mg once daily for 6 weeks. Arm B (consists of chronic HCV genotype 1 infected participants with cirrhosis): participants will receive a combination therapy of SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. A sub-study will be performed at a selected study site, where only participants who will be eligible to participate in both the main study and the sub-study will be enrolled. Intra-hepatic and plasma HCV ribonucleic acid (RNA) levels; intra-hepatic, peripheral innate and adaptive immune responses during the treatment, will be assessed in the sub-study. Participants' safety will be monitored throughout the study.

Conditions

Hepatitis C Virus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks.

Group Type: EXPERIMENTAL

Simeprevir 150 mg

Intervention Type: DRUG

Simeprevir 150 mg capsule orally once daily.

Daclatasvir 60 mg

Intervention Type: DRUG

Daclatasvir 60 mg tablet orally once daily.

Sofosbuvir 400 mg

Intervention Type: DRUG

Sofosbuvir 400 mg tablet orally once daily.

Arm B

Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks.

Group Type: EXPERIMENTAL

Simeprevir 150 mg

Intervention Type: DRUG

Simeprevir 150 mg capsule orally once daily.

Daclatasvir 60 mg

Intervention Type: DRUG

Daclatasvir 60 mg tablet orally once daily.

Sofosbuvir 400 mg

Intervention Type: DRUG

Sofosbuvir 400 mg tablet orally once daily.

Interventions

Simeprevir 150 mg

Simeprevir 150 mg capsule orally once daily.

Intervention Type: DRUG

Daclatasvir 60 mg

Daclatasvir 60 mg tablet orally once daily.

Intervention Type: DRUG

Sofosbuvir 400 mg

Sofosbuvir 400 mg tablet orally once daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000 international units per milliliter (IU/mL), both determined at Screening
• Participants of Arm A should have evidence of early stages of liver fibrosis, defined by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to platelet ratio index (APRI) score <=1
• Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a METAVIR score F4. In addition, participants should have absence of esophageal varices or presence of small (grade 1) esophageal varices determined by upper gastrointestinal endoscopy, and absence of findings indicative of hepatocellular carcinoma in an ultrasonography
• HCV treatment-naive, defined as not having received treatment with any approved or investigational drug for chronic HCV infection
• Pegylated interferon (PegIFN) and ribavirin (RBV) eligible, defined as not having any contraindication to the use of PegIFN and RBV, in line with the prescribing information for each compound

Exclusion Criteria

A. Main Study:

• Co-infection with HCV of another genotype than genotype 1 and/or human immunodeficiency virus (HIV) type 1 or 2 (positive HIV-1 or HIV 2 antibody test at Screening)
• Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, hepatitis B infection (hepatitis B surface antigen positive), drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator
• Evidence of clinical hepatic decompensation or presence of grade 2/3 esophageal varices
• Any of the protocol defined laboratory abnormalities

B. Sub-study:

• Presence of coagulopathy (hemophilia) or hemoglobinopathy (including sickle cell disease, thalassemia)
• Use of any anti-coagulant (for example, warfarin, heparin) or anti-platelet medications within 1 week of the Screening visit
• Any of the protocol defined laboratory abnormalities

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Bakersfield, California, United States

Jacksonville, Florida, United States

Lutherville, Maryland, United States

Winston-Salem, North Carolina, United States

Knoxville, Tennessee, United States

Arlington, Texas, United States

San Antonio, Texas, United States

Toronto, Ontario, Canada

Countries

United States; Canada

References

Sulkowski MS, Feld JJ, Lawitz E, Felizarta F, Corregidor AM, Khalid O, Ghalib R, Smith WB, Van Eygen V, Luo D, Vijgen L, Gamil M, Kakuda TN, Ouwerkerk-Mahadevan S, Van Remoortere P, Beumont M. Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. J Viral Hepat. 2018 Jun;25(6):631-639. doi: 10.1111/jvh.12853. Epub 2018 Feb 6.

Reference Type: DERIVED

PMID: 29274193 (View on PubMed)

Other Identifiers

TMC435HPC2013

Identifier Type: OTHER

Identifier Source: secondary_id

CR105963

Identifier Type: -

Identifier Source: org_study_id