| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| chronic hepatitis C infection |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 11.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008912 |
| E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
| 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 whether 48-week triple therapy peg-IFNα2a 180 μg once weekly + ribavirin 1000 or 1200 mg/day + Debio 025 600 mg significantly increases the proportion of patients who achieve SVR at Week 72 (i.e. HCV RNA < 10 IU/mL 72 weeks after treatment start) compared with standard 48-week peg IFNα2a 180 μg once weekly + ribavirin 1000 or 1200 mg/day therapy (SOC) in treatment naïve chronic hepatitis C genotype 1 patients. |
|
| E.2.2 | Secondary objectives of the trial |
1.To evaluate whether 24-week triple therapy peg-IFNα2a + ribavirin + Debio 025 significantly increases the proportion of patients who achieve SVR at Week 72 compared to SOC treatment.
2. To evaluate whether the 24-/48-week response-guided triple therapy peg-IFNα2a + ribavirin + Debio 025 significantly increases the proportion of patients who achieve SVR at Week 72 compared to SOC treatment. 3.To evaluate whether any of the different peg-IFNα2a + ribavirin + Debio 025 triple therapies significantly increase the proportion of patients who achieve SVR 12 , independently of treatment duration, compared to SOC treatment.
4.To evaluate whether any of the different peg-IFNα2a + ribavirin + Debio 025 triple therapies significantly increase the proportion of patients who achieve SVR 24 independently of treatment duration, compared to SOC treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Males or females aged ≥18 and ≤65 years; 2. BMI between ≥18 and ≤ 32 kg/m2; 3. HbsAg negative and HIV-1 negative; 4. Serological diagnosis of chronic hepatitis C viral infection genotype 1 for > 6 months; 5. Chronic liver disease consistent with chronic hepatitis C infection on a biopsy or FibroScan® obtained within the past 24 months (36 months for patients with incomplete/transition to cirrhosis) 6. Previously untreated for HCV infection (approved or investigational drug); 7. Plasma HCV RNA level lower limit ≥100 IU/ml assessed by qPCR or equivalent; no upper limit; 8. Neutrophil count ≥1500/µL; Hb ≥12g/dL for females and ≥13g/dL for males; platelets ≥ 90 000/µL 9. Patients with incomplete/transition to cirrhosis on biopsy or an elasticity score between 9.5 and 14 kPa on FibroScan must have an US, CT scan, or MRI scan without evidence of hepatocellular carcinoma (within 2 months prior to randomization) and a serum AFP < 100 ng/mL; 10. ASAT and ALAT < 5 times the upper limit of normal; 11. Normal or compensated liver function and absence of complicated portal hypertension as documented by the following: a. No history of bleeding oesophageal varices; b. Absence of ascites; c. Absence of encephalopathy; d. Albumin ≥ 35 g/L; e. Total bilirubin ≤ 1.8 mg/dL (≤ 30µmol/L); f. Prothrombin (INR ≤ 1.5); 12. Creatinine clearance > 50 mL/min; 13. TSH within normal range; 14. All patients should be advised on Debio 025 and ribavirin foetotoxicity: a. Females may participate if they are surgically sterile or post-menopausal. Pre-menopausal females may participate if they use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 4 months after the last Debio 025 or ribavirin dose. b. Male patients must be surgically sterile or use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 7 months after the last Debio 025 or ribavirin dose. 15. Signed informed consent before any study procedures; 16. Negative pregnancy test within one week of first investigational product administration for female patients of child bearing potential. |
|
| E.4 | Principal exclusion criteria |
| 1. Treatment with any investigational drug within 6 months prior to the first dose of investigational product; 2. HCV genotype different from genotype 1; 3. Any previous HCV treatment (approved or investigational); 4. Histologic evidence of complete hepatic cirrhosis (including compensated cirrhosis) based on a previous liver biopsy (if available) or an elasticity score of ≥14 kPa on FibroScan; 5. Ongoing or recent use of any other medication (including over the counter medication and herbal products) within 2 weeks before study start or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of CYP450 3A, substrates of P-gP, or substrates/inhibitors of OATPs, MRP2, or BSEP and are mentioned in the list of unauthorised medications; 6. Any medical contraindications to peg-IFNα2a and/or ribavirin treatment; 7. Any other cause of relevant liver disease other than HCV including but not limited to HBV, drug- or alcohol-related cirrhosis, autoimmune hepatitis, haemochromatosis, Wilson’s disease, NASH, PSC, or PBC; 8. Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrolment or could interfere with the patient participating in and completing the study. Patients with risk factors (hypertension or diabetes) need to have an ophthalmologic investigation (including fundoscopy) 9. History of moderate, severe, or uncontrolled psychiatric disease, especially depression, including a history of hospitalisation or prior suicidal attempt; 10. Uncontrolled arterial hypertension, i.e. patients with systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg; 11. History of pancreatitis, uncontrolled diabetes mellitus or retinopathy; 12. ANA titre >1:640 at screening and/or evidence of autoimmune hepatitis on liver biopsy; 13. Alcohol consumption > 20 g/day for females and > 30 g/day for males; 14. History of major organ transplantation with an existing functional graft; 15. Pregnancy or lactation; 16. Haemoglobinopathies (thalassaemia major, sickle cell anaemia or drepanocytosis); 17. Familial history of severe neonatal cholestasis or pregnancy cholestasis; 18. Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is ≥ 20% within 2 years. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients achieving SVR at Week 72 (HCV RNA < 10 IU/mL 72 weeks after treatment start). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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