E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus (HCV) genotype-1b Infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of a 12- or 24-week treatment regimen of simeprevir in combination with daclatasvir, as measured by SVR12, in treatmentnaïve, chronic HCV genotype 1b-infected subjects who have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4). |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of a 12- or 24-week treatment regimen containing simeprevir and daclatasvir with respect to the percentage of subjects achieving SVR4 and SVR24.
- To evaluate the incidence of on-treatment failure.
- To evaluate the incidence of viral relapse.
- To determine/characterize emerging NS3/4A and NS5A mutations in all subjects not achieving SVR.
- To evaluate safety and tolerability of a 12- or 24-week treatment regimen containing simeprevir and daclatasvir. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must have chronic Hepatitis C virus (HCV) genotype 1b or genotype 4 infection confirmed at Screening
- Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at Screening
- Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 [baseline]). Liver disease will be staged based on one of the following methods.
a) Shear wave elastography (Fibroscan) within less than or equal to (<=) 6 months before Screening or between Screening and Day 1 (baseline). METAVIR F3 > 9.6 Kilopascals (kPa) and the cut-off for
cirrhosis is greater than or equal to (>=) 14.6 kPa.
b) A biopsy documenting METAVIR F0-F4. Biopsy performed within the 24 months before Screening will be accepted for participants with METAVIR score F0-F3. For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable
- Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma
- Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2)
- Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug) |
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E.4 | Principal exclusion criteria |
- Participant has co-infection with HCV of another genotype.
a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b.
b) Participant who has HCV genotype 4 has coinfection with HCV of a genotype other than genotype 4
- Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening
- Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy)
- Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis)
- Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening 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 has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening)
- Participant has received a solid organ transplant |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants With Sustained Virologic Response 12 Weeks After end of Study Drug Treatment (SVR12) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after end of treatment |
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E.5.2 | Secondary end point(s) |
1- Percentage of Participants With Sustained Virologic Response 12 Weeks After end of Study Drug Treatment (SVR12)
2- Percentage of Participants with SVR 4 Weeks After end of Study Drug Treatment (SVR4) and SVR 24 Weeks After end of Study Drug Treatment (SVR24)
3- Percentage of Participants with On-treatment Failure
4- Percentage of Participants with viral breakthrough
5- Percentage of Participants With Viral Relapse |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Week 24 or Week 36
2- For SVR4: Week 16 or 28; for SVR24: Week 36 or 48
3- Week 12 or Week 24
4- Week 12 or Week 24
5- Week 12 or Week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |