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

Hepatitis C Virus Clinical Trial

— ACCORDION-1  

Official title:

A Phase 2, Randomized, Open-label Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 6 or 8 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Subjects With Chronic Hepatitis C Virus Genotype 1 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02349048
• Other study ID #: CR105963
• Secondary ID: TMC435HPC2013
• Status: Completed
• Phase: Phase 2
• First received: January 22, 2015
• Last updated: June 27, 2016
• Start date: January 2015
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: May 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Simeprevir 150 mg
Simeprevir 150 mg capsule orally once daily.
• Daclatasvir 60 mg
Daclatasvir 60 mg tablet orally once daily.
• Sofosbuvir 400 mg
Sofosbuvir 400 mg tablet orally once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response at 12 Weeks After end of Study Drug Treatment (SVR12)	Participants who will have hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ) detectable or undetectable, 12 weeks after the actual end of study drug treatment.	12 weeks after end of study drug treatment (up to Week 20)	No
Secondary	Percentage of Participants With On-treatment Virologic Response	Participants who will have HCV RNA	Baseline up to Week 6 (Arm A) or Week 8 (Arm B)	No
Secondary	Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After end of Study Drug Treatment	Participants who will have HCV RNA	SVR4: 4 weeks after end of study drug treatment; SVR24: 24 weeks after end of study drug treatment	No
Secondary	Percentage of Participants With On-treatment Failure	Participants who have confirmed detectable HCV RNA at the actual end of study drug treatment.	Baseline up to Week 6 (Arm A) or Week 8 (Arm B)	No
Secondary	Percentage of Participants With Viral Relapse	Participants who will not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.	During follow-up (Up to Follow-up Week 24)	No
Secondary	Change from Baseline in HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants not Achieving SVR	Pre-treatment polymorphisms in the HCV nonstructural protein 3/4A (NS3/4A), NS5A and NS5B regions in all participants and relevant changes in the HCV NS3/4A, NS5A and NS5B regions in participants not achieving SVR will be described.	Screening up to Follow-up Week 24	No
Secondary	Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR	Participants who achieve SVR with or without an NS3 Q80K polymorphism at Baseline.	Screening up to Follow-up Week 24	No