E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C genotype 2 and 3 infection. |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C is a viral infection of the blood which damages the liver. |
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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 | 18.0 |
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 |
The primary objective is to evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following directly observed PEG-IFN alfa-2b (1.5 μg/kg weekly, to a maximum of 150 μg/week) in combination with self-administered ribavirin (800-1400 milligrams daily) for 12 weeks in participants with non-quantifiable (<15 IU/ml detected and <15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy, and for 24 weeks in participants with quantifiable (≥15 IU/ml) HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy. In this feasibility study, the primary endpoint measurement of efficacy of treatment will be SVR12. |
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E.2.2 | Secondary objectives of the trial |
- to evaluate the percentage adherent to therapy (>80% of PEG-IFN, >80% of RBV, >80% of time)
- to evaluate safety and tolerability
- to evaluate the rate of recruitment
- to compare the percentage of patients with ETR and SVR24 among those who receive HCV therapy for 12 weeks (non-quantifiable HCV RNA [i.e. <15 IU/ml detected and <15 IU/ml undetected] or undetectable HCV RNA on qualitative assay at week 4) and 24 weeks (quantifiable HCV RNA [i.e. ≥15 IU/ml] or detectable HCV RNA on qualitative assay at week 4)
- to evaluate the change in illicit drug use during treatment
- to evaluate the change in opiate substitution therapy during treatment
- to evaluate the change in depression and suicidal ideation during treatment
- to evaluate the change in health related quality of life during treatment
- to evaluate the percentage of enrolled patients with a satisfactory completed CRF
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants 18 years of age or older.
2. Chronic HCV infection (HCV antibody and/or detectable HCV RNA in plasma ≥ 6 months, and detectable HCV RNA at screening).
3. HCV genotype 2 or 3 infection.
4. Active injection drug use (defined as injection drug use within the 24 weeks prior to consent) OR currently receiving opiate substitution therapy.
5. Compensated liver disease (Child-Pugh class A), where the following criteria must be met:
a. INR< 1.8
b. No ascites (present or ever)
c. No hepatic encephalopathy (present or ever)
d. No bleeding varices (present or ever)
6. Patients with biopsy proven or suspected (Fibroscan > 10KPa or clinical signs) cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP <100 ng/mL within 2 months prior to screening.
7. Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug.
8. All fertile males and females must be using effective contraception (see section 7.3) during treatment and during the 28 weeks after treatment end.
9. Participants have voluntarily signed the informed consent form. |
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E.4 | Principal exclusion criteria |
1. Echocardiographic findings or a medical history suggesting current or previous endocardititis. Baseline 12-lead ECG suggesting a contraindication to treatment with pegylated interferon alfa 2b and ribavirin.
2. Active bacterial or mycobacterial infection.
3. Women with ongoing pregnancy or breast feeding.
4. Interferon or ribavirin therapy at any previous time.
5. Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) *6 months prior to the first dose of study drug.
6. Any investigational drug 6 weeks prior to the first dose of study drug.
7. HCV genotype 1, 4, 5, 6, or 7 infection.
8. HIV infection (positive test at screening for anti-HIV Ab)
9. Hepatitis B virus infection (positive test at screening for HBsAg)
10. Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures).
11. History or other evidence of decompensated liver disease.
12. Neutrophil count <1500 cells/mm3 or platelet count ≤100,000 cells/mm3 at screening.
13. Serum creatinine level >1.5 x upper limit of normal at screening.
14. Ongoing severe psychiatric disease, especially depression, as judged by the treating physician.
15. Frequent drug use that is judged by the treating physician to compromise treatment safety.
16. History of a severe seizure disorder or current anticonvulsant use.
17. History of immunologically mediated disease, severe chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
18. Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range).
19. Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.
20. Inability or unwillingness to provide informed consent or abide by the requirements of the study.
21. Male partners of women who are pregnant.
22. Hemoglobin <12 g/dL (<7.4 mmol/L) in women or <13 g/dL (<8.1 mmol/L) in men at screening.
23. Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic.
24. Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated. |
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E.5 End points |
E.5.1 | Primary end point(s) |
RVR (rapid virological response) defined as undetectable HCV RNA at week 4 will be the determinant of treatment duration.
SVR12 defined as the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (week 24-shortened duration; week 36-standard duration). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
RVR will be assessed after 4 weeks of treatment.
SVR12 assessment will be made 24 weeks after commencing treatment in the short duration arm, and 36 weeks after commencing treatment in the standard duration arm. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Australia |
Canada |
Switzerland |
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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
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End of trial is defined as the last visit of the last subject in 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |