E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 for this study is to analyse the impact of inhibition of viral replication by interferon-free therapy consisting of Sofosbuvir and Daclatasvir (±Ribavirin) on the phenotype and function of the innate immune cells and HCV-specific T-cells, in treatment-naive or previously relapsed chronic hepatitis C patients with GT-1, -3 or -4 infection.
|
|
E.2.2 | Secondary objectives of the trial |
- To evaluate if a shortened treatment duration of 12 weeks with Sofosbuvir and Daclatasvir (±Ribavirin) also results in high sustained virological response rates in subjects infected with HCV genotype 3 and 4; - Evaluation of: o Rapid viral response (RVR) rates on-treatment with SOF + DCV ± RBV; o SVR 4 and -24 rates on-treatment with SOF + DCV ± RBV - Evaluation of tolerability and safety as measured by the frequency of discontinuations due to adverse events (AEs) and serious adverse events (SAEs).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed written informed consent - Willingness to sign the written ICF. 2. Target population - Previous documentation of positive HCV serology (HCV antibody or HCV RNA) at least 24 weeks prior to enrollment to study, OR Positive HCV serology (HCV antibody or HCV RNA) with a prior remote risk factor (more than 24 weeks prior to Screening) for the acquisition of hepatitis C. - Subjects infected with HCV genotype 1, 3 or 4 on screening laboratory test OR previous availaible documentation of HCV genotype 1,3 or 4 genotype. - Treatment-naïve to or relapsed after IFN-alpha based therapies (including first generation PI failures). Relapse is defined as the recurrence of HCV RNA following the termination of a full course of treatment and after having achieved an undetectable HCV RNA during treatment. 3. Age and reproductive status - Age: 18 - 65 years - Subjects must agree to use birth control (condoms) from the time of dosing until 90 days after the follow-up visit; male or female patients who are surgically sterile need not to employ a method of contraception 4. Laboratory test findings - Screening hematology, clinical chemistries, coagulation and urinalysis are not clinically significant and the following criteria are met: o Platelets >50x109/L o Total white blood cells >3.0x109/L and absolute neutrophil count >1.5x109/L o Hemoglobin >6.8 mmol/L for females and >7.4 mmol/L for males o Total and direct bilirubin < 2 x ULN o ALT < 10 x ULN o Serum creatinine within normal limits and estimated creatinine clearance rate as calculated by the Cockcroft-Gault formula >50 mL/min - Negative results on the following screening laboratory tests: HBsAg and HIV antibody OR previous availaible documentation within 1 year before screening of HBsAg and HIV antibody negativity.
|
|
E.4 | Principal exclusion criteria |
- Other known cause of liver disease except for CHC - History or symptoms of decompensated liver disease: Child-Pugh Class B or C, including ascites, hepatic encephalopathy, esophageal variceal bleeding, or other signs of hepatic insufficiency or portal hypertension - History of hepatocellular carcinoma - Concurrent clinically significant medical diagnosis (other than hepatitis C-related conditions) that would potentially interfere with the subjects study compliance or confound study results - History of relevant drug and/or food allergies
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Immune response o Baseline versus end-of-treatment versus follow-up o Patients with SVR versus patients with non-SVR o Patients with genotype 1 versus 3 versus 4
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During and after therapy. |
|
E.5.2 | Secondary end point(s) |
- SVR12 in the study population - Proportion of patients with HCV RNA < LLOD at 4 and 24 weeks after cessation of therapy - Proportion of patients with HCV RNA < LLOD at week 4 during treatment - Any AE leading to discontinuation of the study drug
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
During and after therapy. |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 3 |
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 | No |
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
|
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |