Hepatitis C, ChronicPhase 2NCT01938625
A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
A Phase 2 study testing Simeprevir, Daclatasvir and Ribavirin in people with Hepatitis C, Chronic, run by Janssen R&D Ireland at 6 sites in 3 countries.
Trial summary
The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- Simeprevir, Daclatasvir and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 12 Dec 2013to 28 Jul 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver transplant between 6 months and 10 years prior to the screening visit
- Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening
- Screening HCV ribonucleic acid level greater than 10,000 IU/mL
- HCV treatment-naïve participants must not have received post orthotopic liver transplant treatment with any approved or investigational drug for the treatment of HCV
- Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior to the screening visit
Who cannot join
- Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy)
- Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis
- Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavirin
- Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive)
- Multi-organ transplant that included heart, lung, pancreas, or kidney
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
About this study
Official title: Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when administered as a combinational regimen in post-orthotopic liver transplantation (OLT) participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with respect to the proportion of HCV genotype 1b infected post-OLT participants achieving sustained virologic response 12 weeks after end of treatment.
Read the detailed description
This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.
- Conditions
- Hepatitis C, Chronic
- Being tested
- Simeprevir, Daclatasvir, Ribavirin, Cyclosporine, Tacrolimus
- Keywords
- Hepatitis C, Chronic, Recurrent Chronic Hepatitis C, Pharmacokinetics, Simeprevir, Daclatasvir, Ribavirin, Orthotopic Liver Transplantation, TMC435, BMS-790052, RBV
- 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.
SimeprevirDrug
Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.
DaclatasvirDrug
Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.
RibavirinDrug
Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.
CyclosporineDrug
Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks.
TacrolimusDrug
Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy. Receives: Drug: Simeprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Cyclosporine; Drug: Tacrolimus |
| Part 2 | Experimental | Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy. Receives: Drug: Simeprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.
Measured: Week 36
Secondary outcomes (7)
Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
Participants were considered to have achieved SVR4 if HCV RNA levels were (<) 25 IU/mL detectable or undetectable at 4 weeks after the end of treatment.
Measured: Week 28
Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
Participants were considered to have achieved SVR 24 if hepatitis C virus ribonucleic acid (HCV RNA) levels were (<) 25 IU/mL detectable or undetectable at 24 weeks after the end of treatment.
Measured: Week 48
Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.
Measured: Weeks 2, 4, 12, and 24
Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.
Measured: Week 4
Number 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 <lower limit of quantification (LLOQ) while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to adverse events (AEs), withdrawal of consent).
Measured: Up to Week 24 after actual EOT (week 24)
Number of Participants With Viral Breakthrough
Viral breakthrough is defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.
Measured: Up to week 24
Number 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 24 after actual EOT (week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2013 (estimated)
- Study start12 Dec 2013
- Primary completion27 Apr 2015
- Study completion28 Jul 2015
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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen R&D Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen R&D Ireland Clinical Trial, Study director, Janssen R&D Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01938625
- Sponsor's protocol ID
- CR102639
- Other IDs
- TMC435HPC3016, 2013-002726-23
- Status last verified
- Nov 2018
- First submitted
- 5 Sep 2013
- Last updated
- 21 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Forns X, Berenguer M, Herzer K, Sterneck M, Donato MF, Andreone P, Fagiuoli S, Cieciura T, Durlik M, Calleja JL, Marino Z, Shukla U, Verbinnen T, Lenz O, Ouwerkerk-Mahadevan S, Peeters M, Janssen K, Kalmeijer R, Jessner W. Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study. Transpl Infect Dis. 2017 Jun;19(3). doi: 10.1111/tid.12696. Epub 2017 May 4.
PubMed 28295849
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
- ClinicalTrials.gov ID
- NCT01938625
- Acronym / sponsor ID
- CR102639
- Conditions
- Hepatitis C, Chronic
- Keywords
- Hepatitis C, Chronic, Recurrent Chronic Hepatitis C, Pharmacokinetics, Simeprevir, Daclatasvir, Ribavirin, Orthotopic Liver Transplantation, TMC435
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Janssen R&D IrelandIndustry (pharma, biotech, devices)
- Study start
- 12 Dec 2013 (actual)
- Primary completion
- 27 Apr 2015 (actual)
- Study completion
- 28 Jul 2015 (actual)
- First posted
- 10 Sep 2013 (estimated)
- Results
- Posted 21 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when administered as a combinational regimen in post-orthotopic liver transplantation (OLT) participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with respect to the proportion of HCV genotype 1b infected post-OLT participants achieving sustained virologic response 12 weeks after end of treatment.
Detailed description
This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Simeprevir, Drug: Daclatasvir, Drug: Ribavirin, Drug: Cyclosporine, Drug: TacrolimusParticipants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy. |
| Part 2 | Experimental | Drug: Simeprevir, Drug: Daclatasvir, Drug: Ribavirin, Drug: TacrolimusParticipants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Liver transplant between 6 months and 10 years prior to the screening visit
- Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening
- Screening HCV ribonucleic acid level greater than 10,000 IU/mL
- HCV treatment-naïve participants must not have received post orthotopic liver transplant treatment with any approved or investigational drug for the treatment of HCV
- Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior to the screening visit
Key exclusion criteria (5 listed)
- Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy)
- Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis
- Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavirin
- Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive)
- Multi-organ transplant that included heart, lung, pancreas, or kidney
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 |
|---|---|---|
| SimeprevirParticipants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment. | Drug | Part 1, Part 2 |
| DaclatasvirParticipants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks. | Drug | Part 1, Part 2 |
| RibavirinParticipants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks. | Drug | Part 1, Part 2 |
| CyclosporineParticipants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks. | Drug | Part 1 |
| TacrolimusParticipants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks. | Drug | Part 1, Part 2 |
Primary outcome
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
Time frame: Week 36
Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.
7 secondary outcomes
Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
Time frame: Week 28
Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
Time frame: Week 48
Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Time frame: Weeks 2, 4, 12, and 24
Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Time frame: Week 4
Number of Participants With On-Treatment Failure
Time frame: Up to Week 24 after actual EOT (week 24)
Number of Participants With Viral Breakthrough
Time frame: Up to week 24
Number of Participants With Viral Relapse
Time frame: Up to Week 24 after actual EOT (week 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28295849Forns X, Berenguer M, Herzer K, Sterneck M, Donato MF, Andreone P, Fagiuoli S, Cieciura T, Durlik M, Calleja JL, Marino Z, Shukla U, Verbinnen T, Lenz O, Ouwerkerk-Mahadevan S, Peeters M, Janssen K, Kalmeijer R, Jessner W. Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study. Transpl Infect Dis. 2017 Jun;19(3). doi: 10.1111/tid.12696. Epub 2017 May 4.
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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 R&D Ireland Clinical Trial study director
Janssen R&D Ireland
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simeprevir, Daclatasvir and Ribavirin in people with Hepatitis C, Chronic, run by Janssen R&D Ireland at 6 sites in 3 countries.
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 21 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain, Germany, Poland. 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 21 Nov 2018). 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?
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12) (time frame: Week 36). 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 NCT01938625, 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 21 Nov 2018.