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

NCT02349048 | Completed Phase 2 Results DMC

• 2 other identifiers: CR105963TMC435HPC2013
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 8

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.

Conditions

Hepatitis C Virus

Keywords

Hepatitis C virus; Hepatitis C virus genotype 1; Chronic Hepatitis C Virus Genotype 1 Infection; Liver fibrosis; Cirrhosis; Simeprevir; Daclatasvir; Sofosbuvir

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)

  Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment.

  12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)

Secondary Outcomes (7)

• Percentage of Participants With On-treatment Virologic Response

  Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only)

• Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment

  4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B)

• Percentage of Participants With On-Treatment Failure

  Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B)

• Number of Participants With Viral Relapse

  From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B)

• Number of Participants With Late Viral Relapse

  From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B)

Study Arms (2)

Arm A

EXPERIMENTAL

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.

Drug: Simeprevir 150 mg; Drug: Daclatasvir 60 mg; Drug: Sofosbuvir 400 mg

Arm B

EXPERIMENTAL

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.

Drug: Simeprevir 150 mg; Drug: Daclatasvir 60 mg; Drug: Sofosbuvir 400 mg

Interventions

Simeprevir 150 mg DRUG

Simeprevir 150 mg capsule orally once daily.

Arm A; Arm B

Daclatasvir 60 mg DRUG

Daclatasvir 60 mg tablet orally once daily.

Arm A; Arm B

Sofosbuvir 400 mg DRUG

Sofosbuvir 400 mg tablet orally once daily.

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (8)

Unknown Facility

Bakersfield, California, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Lutherville, Maryland, United States

Location

Unknown Facility

Winston-Salem, North Carolina, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Arlington, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 29274193 DERIVED

MeSH Terms

Conditions

Hepatitis C; Liver Cirrhosis; Fibrosis

Interventions

Simeprevir; daclatasvir; Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Limitations and Caveats

The sample size in Arm B (participants with cirrhosis) was small (n=9).

Results Point of Contact

• Title: Associate Director, Medical Department
• Organization: Janssen R&D BE

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: January 28, 2015
• Study Start: January 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 1, 2017
• Results First Posted: March 1, 2017

Record last verified: 2017-01

Locations

US (7); CA (1)