Phase 2
Completed N=40
An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
Hepatitis C, Chronic
Source: ClinicalTrials.gov NCT02262728 ↗
Enrolled (actual)
40
Serious AEs
35.0%
Results posted
Feb 2017
Primary outcomePrimary: Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) — 100; 100 Percentage of Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) |
100; 100 | — |
| SECONDARY Percentage of Participants With On-Treatment Virologic Response |
72.2; 76.2; 61.1; 38.1; 27.8; 23.8 | — |
| SECONDARY 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) |
100; 100; 100; 100 | — |
| SECONDARY Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment in Participants Not Achieving SVR |
— | — |
| SECONDARY Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) |
137.8; 60.9; 119.1; 83.5; 34.8; 32.3 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
6.00; 8.00; 6.00; 8.00; 3.00; 4.00 | — |
| SECONDARY 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) |
113835; 142162; 98568; 207221; 16487; 17858 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
6976; 7726; 6029; 10498; 1187; 1145 | — |
| SECONDARY Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
3133; 4363; 2639; 6955; 414; 519 | — |
| SECONDARY Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
3577; 5218; 3160; 8577; 494; 646 | — |
| SECONDARY Percentage of Participants With On-treatment Failure |
0; 0 | — |
| SECONDARY Percentage of Participants With Viral Relapse |
— | — |
| SECONDARY Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up |
78.9; 85.7 | — |
Eligibility Criteria
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) 7 to 9 (extremes included)
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
Data sourced from ClinicalTrials.gov (NCT02262728). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.