| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| 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 |
To evaluate the efficacy of Albuferon in combination with ribavirin in IFNα treatment-naïve subjects with chronic hepatitis C genotype 1.
To evaluate the safety of Albuferon in combination with ribavirin in IFNα treatment-naïve subjects with chronic hepatitis C genotype 1.
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| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Have the ability to understand the requirements of the study, provide written informed consent (including consent for use and disclosure of research-related health information) and comply with the study protocol procedures.
2. Age 18 to 65 years inclusive.
3. Have a clinical diagnosis of chronic hepatitis C established on the basis of:
• detectable hepatitis C virus (HCV RNA) during the screening period, and
• at least a 6 month history of exposure to risk factors for HCV with a positive serum antibody test to HCV.
4. Are infected with HCV genotype 1.
5. Subjects must interferon naïve, i.e., have never been treated with an interferon alfa (IFNα) product (eg, INTRON®A, Infergen®, Roferon® or a pegylated IFNα product) or an IFNα combination product (eg, Rebetron® or a pegylated IFNα combination product). Subjects who previously received 2 doses of Albuferon in a treatment naïve dose finding study (ALFR-HC03CA protocol) are eligible provided Albuferon was well tolerated with no Grade 4 or serious adverse events and provided they meet all other criteria.
6. Have compensated liver disease with the following minimum hematologic and biochemical criteria: white blood cell (WBC) count ≥ 3,000/mm3 (3.0 x 109/L), absolute neutrophil count (ANC) ≥ 1,800/mm3 (1.8 x 109/L), platelets ≥ 100,000/mm3 (100 x 109/L), hemoglobin (Hb) ≥ 13 g/dL (8.07 mmol/L) for males or ≥ 12 g/dL (7.45 mmol/L) for females, serum creatinine within normal limits (WNL).
7. Serum glucose value of ≤ 140 mg/dL (≤ 7.8 mmol/L). Results > 140 mg/dL (> 7.8 mmol/L) require a HbA1c ≤ 7.5%. Regardless of screening glucose, HbA1c must be ≤ 7.5% for diabetic subjects, whether on medication or diet controlled.
8. Normal pre-therapy ocular examination (includes fundoscopic and retinal examination) within 1 year of Day 0 in subjects with a history of diabetes or hypertension.
9. Screening EKG without clinically significant abnormalities or evidence of chronic heart disease.
10. Thyroid stimulating hormone (TSH) within normal limits (WNL), whether or not on medication.
11. Alpha fetoprotein (AFP) value WNL obtained within 1 year prior to Day 0. If AFP value is above the upper limit of normal (ULN), the subject must have a negative imaging study (eg, ultrasound, CT scan or MRI) obtained within 6 months prior to Day 0 to show no evidence of focal mass suggestive of hepatoma and/or ascites.
12. Any woman with an intact uterus, regardless of age (unless amenorrheic for the previous 24 months) must have a negative blood pregnancy test at screening.
13. Women who are not exempt from pregnancy testing must agree to practice a medically accepted method of contraception over the course of the study and for 6 months after the last dose of ribavirin.
14. All males must agree to practice a medically accepted method of contraception over the course of the study and for 6 months after the last dose of ribavirin.
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| E.4 | Principal exclusion criteria |
1. Evidence of decompensated liver disease including those subjects with a past history or presence of ascites, bleeding varices or hepatic encephalopathy.
2. Laboratory values (with the exception of ALT and AST) that are Grade 3 or greater by the modified Division of Microbiology and Infectious Diseases (DMID) Toxicity Tables. Subjects with Grade 1 or stable Grade 2 laboratory values (excluding those specified in the inclusion criteria) that are not considered clinically significant by the Principal Investigator may be enrolled.
3. Pregnant or lactating female.
4. Males with a pregnant partner.
5. A positive test for serum antibodies to the human immunodeficiency virus (HIV-1).
6. A positive test for serum hepatitis B virus surface antigen (HBsAg).
7. Clinical diagnosis of other causes of chronic liver disease. This includes but is not limited to hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, alcoholic liver disease, hemochromatosis, Wilson’s Disease, or α1-antitrypsin deficiency.
8. A history of moderate, severe or uncontrolled psychiatric disease, especially depression, including a history of hospitalization or prior suicidal thoughts/attempt. However, subjects with a history of mild, stable depression may be considered provided that a pretreatment assessment (including a Hospital Anxiety and Depression Scale (HADS) score of ≤ 8) of the subject’s affective status supports that the subject is clinically stable. Subjects with a HADS score of > 8 will require further clinical evaluation for depression prior to inclusion into the study. The investigator will formulate a management plan prior to treatment for these subjects, and will review the subject’s affective status at every visit.
9. A history of immunologically mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, sarcoidosis, systemic lupus erythematosus).
10. A history of seizure disorder.
11. A history or other clinical evidence of chronic cardiac disease (eg, angina, congestive heart failure, uncontrolled hypertension, significant arrhythmia).
12. A history or other clinical evidence of chronic pulmonary disease (eg, chronic obstructive pulmonary disease) associated with functional impairment.
13. History of organ transplant other than cornea and hair transplant.
14. History of known hemoglobinopathy (eg, thallasemia, sickle cell anemia).
15. History of known coagulopathy including hemophilia.
16. Evidence of active or suspected malignancy or history of malignancy within the last 5 years (with the exception of adequately treated basal cell carcinoma of the skin).
17. A history of any other medical disease or condition that would make the subject (in the opinion of the investigator) unsuitable for the study.
18. A current drug or alcohol addiction (subjects who have a documented addiction-free period of at least 1 year may be enrolled based on the clinical judgment of the investigator).
19. A positive alcohol or drug screen (amphetamines, barbiturates, opiates, or cocaine) unless there is a medical reason, such as use of an approved medication for a condition that will not (in the clinical judgment of the investigator) confound the evaluation of the study agent.
20. Requirement for concomitant theophylline.
21. Requirement for chronic systemic corticosteroids (prednisone equivalent of > 10 mg/day).
22. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 28 days prior to Day 0.
23. Hypersensitivity to any interferon product or ribavirin.
24. Received silymarin (milk thistle) or glycyrrhizin within 28 days prior to Day 0.
25. Received any experimental agent within 28 days prior to Day 0.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Sustained virologic response (SVR), defined as undetectable
HCV RNA at 24 weeks after the end of therapy.
Safety Endpoints: The major safety endpoints are the common side effects of IFNα therapy including flu-like symptoms, depression, and hematologic abnormalities. Flu-like symptoms include fever, chills, headache, fatigue, malaise, nausea, vomiting, arthralgia, and myalgia. The incidence, severity, and duration of these major endpoints will be summarized through Week 24 and Week 48, as well as at the 12-week follow-up visit. |
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| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | 2 |
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