Clinical trial NCT02349048: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)
timeFrame: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)
Secondary outcomes:
measure: Percentage of Participants With On-treatment Virologic Response
timeFrame: Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only)
measure: Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment
timeFrame: 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)
measure: Percentage of Participants With On-Treatment Failure
timeFrame: Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B)
measure: Number of Participants With Viral Relapse
timeFrame: From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B)
measure: Number of Participants With Late Viral Relapse
timeFrame: From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B)
measure: Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR
timeFrame: Up to Week 30 for Arm A and up to Week 32 for Arm B
measure: Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR
timeFrame: up to Week 30 for Arm A and Week 32 for Arm B
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Lutherville
country: United States
state: Maryland
city: Winston Salem
country: United States
state: North Carolina
city: Knoxville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Toronto
country: Canada
state: Ontario
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.