E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C infection |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis C infection |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019751 |
E.1.2 | Term | Hepatitis C virus |
E.1.2 | System Organ Class | 100000074171 |
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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 demonstrate the efficacy (by achieving high sustained virologic response 12 weeks post dosing [ SVR12] rate) and safety of 8 weeks of treatment with the GLE/PIB combination regimen in treatment naïve adults with HCV GT 1 - GT6 infection with APRI ≤ 1. The primary efficacy objective will be assessed based on modified intention-to-treat (mITT) population across genotypes HCV GT1 - GT6. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To demonstrate the efficacy (by achieving high SVR12 rate) of 8 weeks of treatment with the GLE/PIB combination regimen in treatment naïve adults with HCV GT1 - GT6 infection with APRI ≤ 1 based on ITT population.
• Assess the percentage of subjects with HCV on-treatment virologic failures across GTs in adults with HCV GT1 - GT6 infection with APRI ≤ 1 based on ITT population.
• Assess the percentage of subjects with HCV virologic relapse across GTs in adults with HCV GT1 - GT6 infection with APRI ≤ 1 based on ITT population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult male or female, at least 18 years old at the time of screening.
2. Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug:
• Platelets ≥ 150.000 cells/mm3
• Alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 10 × ULN
• Direct bilirubin ≤ ULN
• Albumin ≥ lower limit of normal (LLN)
• Calculated creatinine clearance (using Cockcroft-Gault method) ≥ 30 mL/min
• A negative hepatitis B surface antigen (HBsAg), and negative anti-hepatitis B core(HBc) or; hepatitis B virus (HBV) DNA < LLOQ in subjects with isolated positive anti-HBc (i.e., negative HBsAg and Anti hepatitis B surface [HBs])
3. Positive anti- HCV antibody (Ab) AND Plasma HCV RNA viral load ≥ 1000 IU/mL at Screening.
4. Any HCV GT allowed, including HCV GT1-, 2-, 3-, 4-, 5-, and/or 6-infection. Mixed GT and indeterminate GT may be acceptable.
5. APRI SCORE ≤ 1, at time of Screening
6. Subject is treatment naïve, e.g., has never received any other investigational or commercially available anti-HCV agents (e.g.,interferon, peginterferon, ribavirin [RBV], telaprevir, boceprevir, simeprevir, asunaprevir, paritaprevir, grazoprevir, daclatasvir, ledipasvir, ombitasvir, elbasvir, dasabuvir, voxilaprevir or any other anti-HCV agent that is approved during the study). |
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E.4 | Principal exclusion criteria |
1. Cirrhosis or past evidence of cirrhosis, described as:
• previous histologic diagnosis of cirrhosis on liver biopsy, e.g., METAVIR, Batts-Ludwig, Knodell, IASL, Scheuer, or Laennec fibrosis score of > 3, Ishak score of > 4 in any liver biopsy conducted prior to screening, OR
• Any previous transient elastography score of ≥ 12.5 kPa, OR
• Any current or historical clinical evidence of cirrhosis or decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding; radiographic evidence of ascites; or use of lactulose and/or rifaximin for hepatic encephalopathy prophylaxis or treatment.
2. History of hepatocellular carcinoma (HCC) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) across genotypes in adults with HCV GT1 - GT6 based on mITT population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the last dose of study drug |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are:
• Percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) across GTs in adults with HCV GT1 - GT6 based on ITT population
• Percentage of subjects with on-treatment virologic failure based on ITT population
• Percentage of subjects with post-treatment relapse based on ITT population |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Day 1 to end of treatment and end of treatment to 12 weeks after the last dose of study drug. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Canada |
Puerto Rico |
Russian Federation |
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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |