Overview

This trial is active, not recruiting.

Condition hepatitis c, chronic
Treatments simeprevir, daclatasvir, sofosbuvir
Phase phase 2
Sponsor Janssen Research & Development, LLC
Start date September 2014
End date August 2015
Trial size 40 participants
Trial identifier NCT02262728, CR105028, TMC435HPC2010

Summary

The purpose of this study is to assess the efficacy of a 12-week regimen containing simeprevir, daclatasvir and sofosbuvir in participants with decompensated liver disease (the liver function is insufficient) due to genotype 1 or 4 Hepatitis (inflammation of the liver) C virus (HCV) infection by assessing sustained virologic response 12-weeks after the end of study drug treatment (SVR12).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants with Child-Pugh score <7 with evidence of portal hypertension (confirmed by presence of esophageal varices or hepatic venous pressure gradient [HVPG] greater than or equal to 10 millimeter of mercury [mm Hg]) will receive simeprevir (150 milligram [mg] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
simeprevir TMC435
Simeprevir 150 milligram (mg) capsule orally once daily for 12 weeks
daclatasvir BMS-790052
Daclatasvir 60 mg tablet orally once daily for 12 weeks
sofosbuvir GS-7977
Sofosbuvir 400 mg tablet orally once daily for 12 weeks
(Experimental)
Participants with Child-Pugh score 7 to 9 (extremes included) will receive simeprevir (150 mg capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
simeprevir TMC435
Simeprevir 150 milligram (mg) capsule orally once daily for 12 weeks
daclatasvir BMS-790052
Daclatasvir 60 mg tablet orally once daily for 12 weeks
sofosbuvir GS-7977
Sofosbuvir 400 mg tablet orally once daily for 12 weeks

Primary Outcomes

Measure
Percentage of Participants With Sustained Virologic Response 12 Weeks After end of Study Drug Treatment (SVR12)
time frame: Week 24

Secondary Outcomes

Measure
Percentage of Participants with On-treatment Virologic Response
time frame: Up to Week 12
Percentage of Participants with SVR 4 Weeks After end of Study Drug Treatment (SVR4) and SVR 24 Weeks After end of Study Drug Treatment (SVR24)
time frame: Week 16 and Week 36
Percentage of Participants with On-treatment Failure
time frame: Week 12
Percentage of Participants with Viral Relapse
time frame: Week 16, 24 and 36
Change From Baseline in HCV NS3/4A Sequence, NS5A and NS5B at Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 After end of Treatment in Participants not Achieving SVR
time frame: Baseline, Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 after end of treatment
Percentage of Participants with Normalized Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
time frame: Up to Week 276
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir metabolite)
time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Area Under the Plasma Concentration-Time Curve from Time 0 to 24 hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir metabolite)
time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir metabolite)
time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir metabolite)
time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Pre-dose (trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir metabolite)
time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Percentage of Participants with SVR12 who Maintain to have HCV RNA <LLOQ Until the end of 5 years Follow up
time frame: Week 24 up to Week 276

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis - HCV genotype 1 or 4 infection and HCV RNA plasma level >10,000 international unit per milliliter (IU/mL) (both determined at screening) - Presence of cirrhosis, which is defined as a FibroScan with a result of >14.5 kilopascals (kPa) at Screening - HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin [RBV]). Last dose in this previous course should have occurred at least 2 months prior to Screening - Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension [confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (>=) 10 millimeter of mercury (mm Hg)], Panel 2: Child-Pugh B (moderate hepatic impairment) Exclusion Criteria: - Co-infection with any HCV genotype - Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening) - Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) - Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, 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 - Use of any disallowed therapies before the planned first dose of study drugs

Additional Information

Official title A Phase 2 Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of 12 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir, Followed by a 5-Year Post-treatment Long-term Follow-up, in Treatment-naïve and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
Description This is an open-label (all people know which treatment the participants receive) Phase 2 study to investigate the efficacy, safety and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir in treatment-naive (participants have never received HCV treatment with any approved or investigational agent) and treatment - experienced (participants have failed at least one previous course of [Pegylated] interferon [(Peg)IFN], with or without Ribavirin) participants. Participants will be assigned to 1 of 2 panels: Panel 1 (n=20): Child-Pugh score less than (<) 7 with evidence of portal hypertension (confirmed by presence of esophageal varices or HVPG greater than or equal to [>=] 10 mm Hg); Panel 2 (n=20): Child-Pugh score 7 to 9 (extremes included). The total study duration for each participant will be approximately 276 weeks. The study will consist of 3 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (from Week 4 to 16) and follow-up Phase (until 5 years after the actual end of study drug treatment). Participants will receive simeprevir (150 milligram [mg] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.