A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection

NCT ID: NCT02421211

Last Updated: 2019-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-19
• Study Completion Date: 2016-01-27

Brief Summary

The purpose of this study is to evaluate the pharmacokinetic interactions between simeprevir and ledipasvir in a treatment regimen consisting of simeprevir (SMV), sofosbuvir (SOF), and ledipasvir (LDV) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype 1 infection.

Detailed Description

This is an open-label (all people know the identity of the intervention), 2-panel, Phase 2, randomized (study medication assigned to participants by chance) study. The study will consist of 3 study phases: Screening Phase (5 weeks), an Open-label Treatment Phase (70 days for Panel 1 and 56 days for Panel 2), a Post-treatment Follow-up Phase (12 weeks after the actual end of treatment). Participants will receive a combination of the following treatments: Treatment A: SMV 150 milligram (mg) once daily; Treatment B: LDV 90 mg along with SOF 400 mg once daily; Treatment C: SOF 400 mg once daily. Participants will be randomly assigned to Panel 1 (Treatment AC followed by Treatment AB) and Panel 2 (Treatment B followed by Treatment AB). The total study duration will be approximately 27 weeks for participants in Panel 1 and 25 weeks for participants in Panel 2. Participants will be primarily accessed for pharmacokinetic parameters. Participants' safety will be monitored throughout the study.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Panel 1

Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.

Group Type: EXPERIMENTAL

Simeprevir (SMV)

Intervention Type: DRUG

Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.

Ledipasvir (LDV)

Intervention Type: DRUG

Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.

Sofosbuvir (SOF)

Intervention Type: DRUG

Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2.

Panel 2

Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.

Group Type: EXPERIMENTAL

Simeprevir (SMV)

Intervention Type: DRUG

Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.

Ledipasvir (LDV)

Intervention Type: DRUG

Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.

Sofosbuvir (SOF)

Intervention Type: DRUG

Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2.

Interventions

Simeprevir (SMV)

Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.

Intervention Type: DRUG

Ledipasvir (LDV)

Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.

Intervention Type: DRUG

Sofosbuvir (SOF)

Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants with Body Mass Index (weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter kg/m^2, extremes included
• Participants must be treatment-naive (that is, have not received prior treatment with any approved or investigational drug)
• Participants with HCV ribonucleic acid (RNA) plasma levels greater than (>) 10,000 international unit per milliliter (IU/ml) and lower than 6,000,000 international unit per milliliter (IU/ml) at screening
• Participants with absence of cirrhosis confirmed by FibroTest/Fibrosure score less or equal to 0.75 and an aspartate aminotransferase to platelet ration index less or equal to 2 or a Fibroscan less or equal to 14.6 kilopascale (kPA), performed within 6 months prior or during the screening period
• Participants with documented chronic HCV infection: diagnosis of HCV infection >6 months prior to screening, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes consistent with chronic hepatitis in a liver biopsy

Exclusion Criteria

• Participant has infection/co-infection with HCV of a genotype other than genotype 1, human immunodeficiency virus (HIV) type 1 or 2
• Participant has any evidence of liver disease of non-HCV etiology. This includes, but is not limited to acute hepatitis A, active hepatitis B, 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-HC liver disease considered clinically significant by the investigator
• Participant with significant co-morbidities, conditions or clinical significant findings during screening assessments that in the opinion of the investigator could compromise the participants' safety or could interfere with the Participant participating in and completing the study
• Participant received an organ transplant (other than cornea or hair transplant or skin graft)
• Participants have key protocol defined laboratory abnormalities

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

Antwerp, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Countries

Belgium

References

Bourgeois S, Horsmans Y, Nevens F, van Vlierberghe H, Moreno C, Beumont M, Vijgen L, van Eygen V, Luo D, Hillewaert V, Van Remoortere P, van de Logt J, Ouwerkerk-Mahadevan S. Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01217-17. doi: 10.1128/AAC.01217-17. Print 2017 Dec.

Reference Type: DERIVED

PMID: 28971875 (View on PubMed)

Other Identifiers

TMC435HPC2017

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000459-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR106992

Identifier Type: -

Identifier Source: org_study_id