E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus (HCV) genotype-1 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 | 14.1 |
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 |
The primary objective is to evaluate the antiviral efficacy of TMC435 in combination with PegIFNalpha-2a and RBV, with respect to the proportion of subjects with SVR24 (1) in the subjects who participated in the placebo group of a Phase II/III TMC435 study, and (2) in the subjects who participated in a selected Tibotec-sponsored Phase I study. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To evaluate the antiviral efficacy of TMC435 in combination with PegIFNalpha-2a and RBV with respect to the proportion of subjects with SVR12.
- To evaluate the on-treatment virologic response to TMC435 in combination with PegIFNalpha-2a and RBV at all time points, with focus on Week 4, Week 12, Week 24, and Week 48.
- To evaluate the incidence of virologic failure during treatment.
- To evaluate the viral relapse rate after treatment.
- To determine the proportion of subjects who meet the criteria for treatment completion at Week 24 in the subgroups of subjects who experienced viral relapse or viral breakthrough in a Phase II/III TMC435 study.
- To determine the viral NS3/4A sequence of subjects with virologic failure.
- To evaluate the safety and tolerability of TMC435 in combination with PegIFNalpha-2a and RBV. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject was previously randomized to the placebo group of a Phase II/III TMC435 study and did not achieve undetectable HCV RNA levels at the end of treatment or relapsed (confirmed detectable HCV RNA) within 1 year after end of treatment.
OR
Subject received short-term (up to 14 days) DAA treatment for HCV infection in a selected Tibotec-sponsored Phase I study on genotype 1;
- Subject must have completed the last study-related assessment in the previous study.
Please refer to the protocol for the complete list of inclusion criteria. |
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E.4 | Principal exclusion criteria |
- Subject shows evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy);
- Subject has co-infection with nongenotype 1 HCV. Since all subjects have previously participated in a study evaluating subjects with genotype 1 HCV infection, this screening test is at the discretion of the investigator, to rule out nongenotype 1 HCV infection in case of clinical signs of acute hepatitis infection and suspicion of possible re-infection;
- Subject has co-infection with HIV type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at Screening);
- Subject has any of the following laboratory abnormalities at screening: platelet count ≤ 90,000/mm3; absolute neutrophil count < 1500 cells/mm3 (blacks: < 1200 cells/mm3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; creatinine >1.5 mg/dL; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 10 x ULN; total serum bilirubin > 1.5 x ULN. Note: Retesting of an abnormal laboratory or urinalysis result that leads to exclusion will be allowed once using an unscheduled visit during the screening period to assess eligibility;
- Subject received any DAA HCV therapy, other than having received short-term (up to 14 days) DAA in a selected Tibotec-sponsored Phase I study;
- Subject prematurely stopped medication in the previous TMC435 study for noncompliance;
- Subject prematurely stopped medication in the previous TMC435 study for safety reasons, and it would therefore be unsafe to repeat treatment at investigator’s discretion.
Please refer to the protocol for the complete list of exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter is the proportion of subjects with SVR24.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subjects will be considered a success if a subject achieves undetectable HCV RNA at EOT and 24 weeks after planned EOT (regardless of treatment completion status) |
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E.5.2 | Secondary end point(s) |
Secondary efficacy parameters include the proportion of subjects:
1 - with SVR12;
2 - with undetectable HCV RNA (< 25 IU/mL undetectable) and/or HCV RNA levels < 25 IU/mL at all time points during treatment and follow-up, with focus on Week 4, Week 12, Week 24, Week 36, and Week 48;
3 - with HCV RNA >1000IU/mL at Week 4 or viral breakthrough, defined as a confirmed increase of > 1 log10 IU/mL in HCV RNA level from the lowest level reached;
4 - with on-treatment virologic failure, i.e., subject discontinued all study medication because he/she met a virologic stopping rule requiring to stop all treatment;
5 - with viral relapse, defined as undetectable HCV RNA (< 25 IU/mL undetectable) at the end of treatment and confirmed detectable HCV RNA during follow-up or detectable HCV RNA at SVR assessments;
6 - with normalized ALT levels at the end of treatment and at SVR assessment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 12 weeks after the end of treatment;
2 - at all time points during treatment and follow-up, with focus on Week 4, Week 12, Week 24, Week 36, and Week 48;
3 - at week 4;
4 - no timepoint,
5 - at the end of treatment (undetectable HCV RNA) and during follow-up or at SVR assessment (detectable HCV RNA);
6 - at the end of treatment and at SVR assessment. |
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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 | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
France |
Germany |
Italy |
Netherlands |
New Zealand |
Norway |
Portugal |
Puerto Rico |
Spain |
Israel |
Mexico |
Poland |
Romania |
Russian Federation |
Slovakia |
Turkey |
Ukraine |
United Kingdom |
United States |
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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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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |