Hepatitis C, ChronicPhase 2NCT02421211

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

A Phase 2 study testing Simeprevir (SMV), Ledipasvir (LDV) and Sofosbuvir (SOF) in people with Hepatitis C, Chronic, run by Janssen Sciences Ireland UC at 4 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hepatitis C, Chronic
What is being tested?: Simeprevir (SMV), Ledipasvir (LDV) and Sofosbuvir (SOF)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 41 participants
Where: 4 sitesBelgium
Study dates: 19 May 2015to 27 Jan 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

4 sites in 1 country.

Belgium4 sites

Study site
Antwerp
Study site
Brussels
Study site
Ghent
Study site
Leuven

Other trials in Belgium

About this study

Official title: A Phase 2, 2-panel, Open-label Randomized Study in Hepatitis C Virus Infected Subjects to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir and Ledipasvir in Treatment-naive Participants.

Read the 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
Being tested: Simeprevir (SMV), Ledipasvir (LDV), Sofosbuvir (SOF)
Keywords: Hepatitis C, Chronic, Simeprevir, Ledipasvir, Sofosbuvir
Medical subject headings: Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT02421211
Study group	Role	What they receive
Panel 1	Experimental	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. Receives: Drug: Simeprevir (SMV); Drug: Ledipasvir (LDV); Drug: Sofosbuvir (SOF)
Panel 2	Experimental	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. Receives: Drug: Simeprevir (SMV); Drug: Ledipasvir (LDV); Drug: Sofosbuvir (SOF)

What is being measured

The primary outcome is the main question the study is designed to answer.

Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
The Cmin is the minimum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Maximum Plasma Concentration (Cmax) of Simeprevir
The Cmax is the maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
The Cmin is the minimum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Maximum Plasma Concentration (Cmax) of Ledipasvir
The Cmax is the maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

Secondary outcomes (14)

Trough Plasma Concentration (Ctrough) of Simeprevir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Measured: Pre-dose on Day 14 and Day 28
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation Index (FI) of Simeprevir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Trough Plasma Concentration (Ctrough) of Ledipasvir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Measured: Pre-dose on Day 14 and Day 28
Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation Index (FI) of Ledipasvir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
Percentage of Participants With On-treatment Virologic Response
On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.
The following thresholds were considered at any time point: less than (<) lower limit of quantification (LLOQ) undetectable, <LLOQ detectable and <LLOQ undetectable/detectable.
Measured: Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)
SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA <LLOQ detectable or undetectable.
Measured: 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <LLOQ while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to AEs, withdrawal of consent).
Measured: Day 70 in Panel 1 and Day 56 in Panel 2
Percentage of Participants With Viral Relapse
Participants who did 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.
Measured: Up to Week 12 follow-up phase after EOT
Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence
Measured: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 May 201527 Jan 2016

First posted20 Apr 2015 (estimated)
Study start19 May 2015
Primary completion10 Nov 2015
Study completion27 Jan 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02421211
Sponsor's protocol ID: CR106992
Other IDs: TMC435HPC2017, 2015-000459-25, 2015
Status last verified: Mar 2019
First submitted: 15 Apr 2015
Last updated: 28 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 28971875

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hepatitis C, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, 2-panel, Open-label Randomized Study in Hepatitis C Virus Infected Subjects to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir and Ledipasvir in Treatment-naive Participants.
ClinicalTrials.gov ID: NCT02421211
Acronym / sponsor ID: CR106992
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic, Simeprevir, Ledipasvir, Sofosbuvir
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 41 participants (actual)
Lead sponsor: Janssen Sciences Ireland UCIndustry (pharma, biotech, devices)
Study start: 19 May 2015 (actual)
Primary completion: 10 Nov 2015 (actual)
Study completion: 27 Jan 2016 (actual)
First posted: 20 Apr 2015 (estimated)
Results: Posted 5 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Panel 1	Experimental	Drug: Simeprevir (SMV), Drug: Ledipasvir (LDV), Drug: Sofosbuvir (SOF)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.
Panel 2	Experimental	Drug: Simeprevir (SMV), Drug: Ledipasvir (LDV), Drug: Sofosbuvir (SOF)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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Simeprevir (SMV)Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.	Drug	Panel 1, Panel 2
Ledipasvir (LDV)Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.	Drug	Panel 1, Panel 2
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.	Drug	Panel 1, Panel 2

Primary outcome

Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Maximum Plasma Concentration (Cmax) of Simeprevir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Maximum Plasma Concentration (Cmax) of Ledipasvir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.

14 secondary outcomes

Trough Plasma Concentration (Ctrough) of Simeprevir
Time frame: Pre-dose on Day 14 and Day 28
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation Index (FI) of Simeprevir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Trough Plasma Concentration (Ctrough) of Ledipasvir
Time frame: Pre-dose on Day 14 and Day 28
Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation Index (FI) of Ledipasvir
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
Percentage of Participants With On-treatment Virologic Response
Time frame: Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)
Time frame: 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
Percentage of Participants With On-treatment Failure
Time frame: Day 70 in Panel 1 and Day 56 in Panel 2
Percentage of Participants With Viral Relapse
Time frame: Up to Week 12 follow-up phase after EOT
Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence
Time frame: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2

Results and safety

Results posted to the registry on 5 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])	20	20
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	20	20

Primary outcome: Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28. Mean (Standard Deviation). Unit: nanogram per Milliliters (ng/mL)

Measure	Panel 1: SMV 150 mg + SOF 400 mg (Day 14) n = 20	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) n = 20
Value	2411 (3778)	6701 (4179)

Panel 1: SMV 150 mg + SOF 400 mg (Day 14) vs Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28): LS means ratio: 4.7 (90% CI 3.4 to 6.5)

Population analysed: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Primary outcome: Maximum Plasma Concentration (Cmax) of Simeprevir

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28. Mean (Standard Deviation). Unit: ng/mL

Measure	Panel 1: SMV 150 mg + SOF 400 mg (Day 14) n = 20	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) n = 19
Value	6767 (6362)	13691 (7775)

Panel 1: SMV 150 mg + SOF 400 mg (Day 14) vs Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28): LS means ratio: 2.3 (90% CI 2.0 to 2.8)

Population analysed: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Primary outcome: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28. Mean (Standard Deviation). Unit: nanogram hour per Milliliters (ng*h/mL)

Measure	Panel 1: SMV 150 mg + SOF 400 mg (Day 14) n = 20	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) n = 19
Value	100492 (115868)	243564 (159124)

Panel 1: SMV 150 mg + SOF 400 mg (Day 14) vs Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28): LS means ratio: 3.1 (90% CI 2.4 to 3.8)

Primary outcome: Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28. Mean (Standard Deviation). Unit: ng/mL

Measure	Panel 2: LDV 90mg/SOF 400mg (Day 14) n = 20	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) n = 18
Value	319 (178)	557 (307)

Panel 2: LDV 90mg/SOF 400mg (Day 14) vs Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28): LS means ratio: 1.7 (90% CI 1.5 to 2.0)

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])	2 of 20 (10%)	17 of 20 (85%)	Not reported
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	0 of 20 (0%)	15 of 20 (75%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28971875Bourgeois 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Janssen Sciences Ireland UC Clinical Trial study director

Janssen Sciences Ireland UC

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Simeprevir (SMV), Ledipasvir (LDV) and Sofosbuvir (SOF) in people with Hepatitis C, Chronic, run by Janssen Sciences Ireland UC at 4 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) (time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02421211, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2019.