A Phase 2 interventional study of Simeprevir and Daclatasvir in Hepatitis C, Chronic, sponsored by Janssen R&D Ireland. Completed at 6 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-11-21.
Sponsored by Janssen R&D Ireland · Phase 2, Interventional, and Treatment
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.
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.
2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.
This study's enrollment of 35 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.
Browse Hepatitis A studies →Janssen R&D Ireland is the lead sponsor of 31 studies on the registry; none are open to participants now.
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Exclusion Criteria:
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.
Drug: Simeprevir · Drug: Daclatasvir · Drug: Ribavirin · Drug: Cyclosporine · Drug: Tacrolimus
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.
Drug: Simeprevir · Drug: Daclatasvir · Drug: Ribavirin · Drug: Tacrolimus
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.
Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.
Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.
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.
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.
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.
Time frame: Week 36
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Up to Week 24 after actual EOT (week 24)
| Milestone | Cyclosporine | Tacrolimus |
|---|---|---|
| Started | 10 | 25 |
| Completed | 10 | 23 |
| Not completed | 0 | 2 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Adverse event | 0 | 1 |
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.
| percentage of participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12) | 100 (69.2 to 100) | 88 (68.8 to 97.5) |
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.
| percentage of participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4) | 100 (69.2 to 100) | 88 (68.8 to 97.5) |
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.
| percentage of participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24) | 100 (69.2 to 100) | 88 (68.8 to 97.5) |
Percentage of participants with detectable and undetectable HCV RNA (\<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.
| percentage of participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Week 2: <25 IU/mL detectable | 30 | 36 |
| Week 2: <25 IU/mL undetectable | 10 | 12 |
| Week 4: <25 IU/mL detectable | 30 | 24 |
| Week 4: <25 IU/mL undetectable | 70 | 68 |
| Week 12: <25 IU/mL detectable | 0 | 0 |
| Week 12: <25 IU/mL undetectable | 100 | 96 |
| Week 24: <25 IU/mL detectable | 0 | 0 |
| Week 24: <25 IU/mL undetectable | 100 | 100 |
Percentage of participants with HCV RNA (\<) 100 IU/mL at week 4 were reported.
| percentage of participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4 | 100 | 100 |
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).
| participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Number of Participants With On-Treatment Failure | 0 | 3 |
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.
| participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Number of Participants With Viral Breakthrough | 0 | 3 |
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.
| participants | Cyclosporine | Tacrolimus |
|---|---|---|
| Number of Participants With Viral Relapse | 0 | 0 |
Collected over Up to 52 Weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cyclosporine | — | 4/10 (40%) | 10/10 (100%) |
| Tacrolimus | — | 4/25 (16%) | 23/25 (92%) |
| Event | Cyclosporine | Tacrolimus |
|---|---|---|
| PyrexiaGeneral disorders | 3/10 | 0/25 |
| DiarrhoeaGastrointestinal disorders | 1/10 | 0/25 |
| Escherichia Urinary Tract InfectionInfections and infestations | 1/10 | 0/25 |
| Genital HerpesInfections and infestations | 1/10 | 0/25 |
| Facial Bones FractureInjury, poisoning and procedural complications | 1/10 | 0/25 |
| SyncopeNervous system disorders | 1/10 | 0/25 |
| Acute Kidney InjuryRenal and urinary disorders | 1/10 | 0/25 |
| Renal ImpairmentRenal and urinary disorders | 1/10 | 0/25 |
| ProstatitisReproductive system and breast disorders | 1/10 | 0/25 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/10 | 0/25 |
| Event | Cyclosporine | Tacrolimus |
|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 7/10 | 11/25 |
| AstheniaGeneral disorders | 5/10 | 7/25 |
| FatigueGeneral disorders | 2/10 | 1/25 |
| HyperbilirubinaemiaHepatobiliary disorders | 2/10 | 2/25 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/10 | 3/25 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 2/10 | 1/25 |
| PruritusSkin and subcutaneous tissue disorders | 1/10 | 5/25 |
| HeadacheNervous system disorders | 1/10 | 4/25 |
| VertigoEar and labyrinth disorders | 0/10 | 3/25 |
| DiarrhoeaGastrointestinal disorders | 1/10 | 3/25 |
| Age, Continuous(years) | Cyclosporine | Tacrolimus | Total |
|---|---|---|---|
| Median | 64.5 (52 to 69) | 61 (27 to 69) | 62 (27 to 69) |
| Sex: Female, Male(Participants) | Cyclosporine | Tacrolimus | Total |
|---|---|---|---|
| Female | 4 | 9 | 13 |
| Male | 6 | 16 | 22 |
| Region of Enrollment(Participants) | Cyclosporine | Tacrolimus | Total |
|---|---|---|---|
| Germany | 1 | 6 | 7 |
| Spain | 3 | 9 | 12 |
| Poland | 0 | 7 | 7 |
| Italy | 6 | 3 | 9 |
This study is completed, as verified in Nov 2018. You cannot join it, but the record below documents what was studied.
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Janssen R&D Ireland