E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Virus (HCV) Infection (Genotypes 1, 2, 3, 4) |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic 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 evaluate Sustained Virologic Response at post treatment Week 12 (SVR12) following treatment with Lambda/RBV/DCV in chronic HCV GT-1, -2, -3 or -4 subjects co-infected with HIV-1. |
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E.2.2 | Secondary objectives of the trial |
1) Evaluate Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR).
2) Evaluate HCV RNA < Lower Limit of Quantification (LLOQ) at 24 weeks post treatment (SVR24).
3) Evaluate the treatment emergent cytopenic abnormalities (anemia as defined by hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750 mm3 and/or thrombocytopenia as defined by platelets < 50,000/ml) during the treatment period.
4) Evaluate the following on-treatment IFN-associated symptoms:
- Flu-like symptoms (as defined by pyrexia or chills or pain)
- Musculoskeletal symptoms (as defined by arthralgia or myalgia or back pain)
5) Evaluate safety as measured by the frequency of discontinuations due to adverse events (AEs), and serious adverse events (SAEs)
6) To assess change in absolute CD4 cell count, percent CD4 cell count, lymphocyte cell count, and platelet count. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• HCV Genotype-1, -2, -3 or -4 treatment naïve;
• Male and females, 18 years of age and above
• HCV RNA ≥ 10,000 IU/mL at screening;
• HIV-1 infection (approximately 200 subjects receiving HAART, approximately 100 subjects not receiving HAART);
• For subjects receiving HAART, HIV RNA must be below < 40 copies/mL at screening and < 200 copies/mL for at least 8 weeks prior to screening;
• CD4 cell count at screening must be ≥ 100 cells/μL if receiving HAART or ≥ 350 cells/μL if not receiving HAART
• Seronegative for HBsAg
• Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2 at screening;
• Subjects with compensated cirrhosis are permitted, but the number of subjects will be capped at approximately 30%. If a subject does not have cirrhosis, a liver biopsy within 3 years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. Fibroscan® or FibroTest are acceptable if performed within 1 year prior to treatment in countries where liver biopsy is not required prior to treatment and where non-invasive imaging tests are approved for staging of liver disease.
• Subjects with mild to moderate hemophilia as defined as:
- Mild – factor level activity of 6-40% OR
- Moderate defined as factor level activity of 1-5%
For additional inclusion criteria, please refer to Protocol section 3.3.1 |
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E.4 | Principal exclusion criteria |
• Any evidence of liver disease other than chronic HCV;
• Subjects infected with HIV-2;
• Diagnosed or suspected hepatocellular carcinoma;
• Decompensated liver disease;
• Presence of AIDS-defining opportunistic infections within 12 weeks prior to study entry;
• Laboratory values: ANC < 1.5 x 109 cells/L (< 1.2 x 109 cells/L for Black subjects), platelet count <90 x 109 cells/L, hemoglobin < 11 g/dL for females, hemoglobin < 12 g/dL for males;
• Subjects (receiving HAART) who had first initiated anti-retroviral therapy within last 8 weeks prior to Day 1; however, if changes are required to a subject’s HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. Subjects should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, < 40 copies/mL;
• Subjects on zidovudine (AZT), didanosine (ddI), or stavudine (d4T);
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Subjects with severe hemophilia (defined as < 1% factor activity level)
For additional exclusion criteria, please refer to Protocol section 3.3.2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with SVR12 defined as HCV RNA < LLOQ (25 IU/mL; target detected or not detected) at 12 weeks post treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Proportion of subjects with RVR and eRVR, where RVR is defined as < LLOQ target not detected at Week 4 and eRVR defined as < LLOQ target not detected at Weeks 4 and 12.
2) Proportion of subjects in each group/duration who achieve HCV RNA < LLOQ target detected or not detected, at end of therapy (SVR24).
3) Proportion of subjects with treatment emergent cytopenic abnormalities (anemia as defined by Hb < 10 g/dL, and/or neutropenia as defined by ANC < 750 mm3 and/or thrombocytopenia as defined by platelets < 50,000 mm3) during the treatment period.
4) Proportion of subjects with the following on treatment IFN-associated symptoms:
a) Flu-like symptoms (as defined by pyrexia or chills or pain)
b) Musculoskeletal symptoms (as defined by arthralgia or myalgia or back pain).
5) Frequency of deaths, serious adverse events (SAEs), discontinuations due to AEs, dose reductions, and severity Grade 3/4 laboratory abnormalities.
6) Absolute and percent change from baseline in the CD4 cell count, lymphocyte cell count, and platelet count. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) RVR at Week 4 and eRVR at Weeks 4 and 12
2) 24 weeks post treatment (SVR24)
3) Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits)
4) From Day 1 to End of Treatment, 24 or 48 weeks: Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits)
5) From Day 1 until the end of treatment, 24 weeks or 48 weeks: Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits)
6) Weeks 4, 8, 12 and 24 (and Week 36 for subjects requiring visit) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers; Outcomes Research; HCV and HIV Resistance Monitoring; Immunogenicity |
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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 | Yes |
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 | 2 |
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 | 33 |
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 |
Belgium |
Canada |
France |
Germany |
Italy |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |