| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C (CHC) genotype 2/3. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008912 |
|
| 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 alb-IFN in combination with ribavirin compared with PEG-IFNα2a in combination with ribavirin in IFNα treatment-naïve subjects with chronic hepatitis C (CHC) genotype 2/3. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety of alb-IFN in combination with ribavirin compared with PEG-IFNα2a in combination with ribavirin in IFNa treatment-naïve subjects with chronic hepatitis C genotype 2/3.
To evaluate the impact on subject vitality of alb-IFN in combination with ribavirin compared with PEG-IFNα2a in combination with ribavirin in IFNα treatment-naïve subjects with chronic hepatitis C, genotype 2/3.
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Exploratory Fibrosis Sub-study: Noninvasive Methods to Assess Liver Fibrosis
Date: 09 October 2006
Version: 00
Additional noninvasive methods to assess liver fibrosis both prior to treatment and in response to therapy will aid physicians in the management of subjects with chronic liver disease. An exploratory study will assess changes in liver stiffness by elastography (FibroScan, Echosense, France) and extent of liver fibrosis and necro-inflammation by FibroSURE, (Imbert-Bismut, 2001) during treatment and in the post-treatment follow-up period. |
|
| 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 years or older.
3. Have a clinical diagnosis of chronic hepatitis C (CHC) and detectable hepatitis C RNA (HCV RNA) during the screening period.
4. Subjects must have had a liver biopsy performed within 2 years of Day 0 (date of 1st treatment) or during screening. The results of this biopsy must be consistent with chronic hepatitis C infection. One Hematoxylin & Eosin (H&E) and 1 Trichrome slide must be available for central reading.
5. Are infected with HCV genotype 2 or 3. Subjects with mixed genotype infection (eg, genotype 1/2, 1/3, 2/3 etc) at screening will not be enrolled into the study. Subjects with mixed genotype 2a/2b or 3a/3b may be enrolled.
6. Are IFN treatment naïve, ie, have never been treated with an interferon product (eg, IFNα product, pegylated IFNα product, consensus IFN product or any experimental IFN product) as monotherapy or in combination with any other agent.
7. Have compensated liver disease with the following minimum hematologic and biochemical criteria: absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 x 109/L), platelets ≥ 90,000/mm3 (90 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).
8. Serum glucose value of ≤ 140 mg/dL (≤ 7.8 mmol/L). If serum glucose is > 140 mg/dL (> 7.8 mmol/L), HbA1c must be ≤ 7.5%. For subjects who are diabetic (whether on medication or diet controlled) HbA1c must be ≤ 7.5%, regardless of screening glucose.
9. Thyroid stimulating hormone (TSH) should be within the normal range whether or not on medication. Subjects with TSH below the lower limit of normal may be enrolled if free T4 is normal and there is no clinical evidence of hyperthyroidism or hypothyroidism.
10. Alpha fetoprotein (AFP) value ≤ 20 ng/mL at screening. If AFP value is > 20 ng/mL, the subject must have had a normal imaging study (CT, MRI or ultrasound) within 6 months of Day 0. If a previous imaging study is not available, then an ultrasound showing no evidence of focal mass suggestive of hepatoma, must be performed during screening.
11. Normal ocular examination (includes fundoscopic and retinal examination) performed at screening.
12. Screening ECG without clinically significant abnormalities.
13. Spirometry within 6 months of Day 0, showing no evidence of clinically significant abnormality.
14. A female subject is eligible to enter the study if she is:
· Not pregnant or nursing.
· Of non-childbearing potential (ie, women who have had a hysterectomy, have both ovaries removed, have a documented tubal ligation or are postmenopausal – defined as 24 months without menses).
· Of childbearing potential (ie, women with an intact uterus and ovaries and no documentation of oviductal or uterine dysfunction that would cause sterility). These women must have a negative blood pregnancy test at screening and a negative urine pregnancy test on Day 0 prior to randomization and agree to 1 of the following:
Complete abstinence from intercourse from the date of screening until 7 months following the last dose of ribavirin.
Consistent and correct use of 1 of the following medically accepted methods of birth control, in addition to a male partner who correctly uses a condom or is sterile prior to the female subject’s entry into the study and is the sole sexual partner for the female subject from the date of screening until 7 months after the last dose of ribavirin:
· implants of levonorgestrel;
· injectable progesterone;
· any intrauterine device (IUD) with a documented failure rate of less than 1% per year;
· oral contraceptives (either combined or progesterone only);
· double barrier method: condom, cervical cap or diaphragm with spermicidal agent;
· transdermal contraceptive patch;
15. All males who are not sterile must agree to either abstain from intercourse or consistently and correctly use a condom while their female partner agrees to use 1 of the appropriate medically accepted methods of birth control listed above from the date of screening until 7 months after their last dose of ribavirin. Males with pregnant partners will not be enrolled in the study. |
|
| 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, AST, GGT) that are Grade 3 or greater by the modified Division of Microbiology and Infectious Diseases (DMID) Toxicity Tables. Subjects with Grade 1 or 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. A history of moderate, severe or uncontrolled psychiatric disease, especially depression, including a history of hospitalization or prior suicidal attempt. Subjects with a history of mild, stable depression may be considered provided that a pretreatment assessment (including a Hospital Anxiety and Depression Scale [HADS] depression subscale score of ≤ 8) of the subject’s affective status supports that the subject is clinically stable. Subjects with a HADS depression subscale score of > 8 will require further clinical evaluation for depression prior to inclusion into the study. The investigator must formulate and document a depression management plan prior to randomization for these subjects, and must review the subject’s affective status according to the plan at every visit.
4. A positive test for serum antibodies to the human immunodeficiency virus (HIV-1).
5. A positive test for serum hepatitis B surface antigen (HBsAg).
6. 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.
7. A history of immunologically-mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, moderate/severe psoriasis, sarcoidosis, systemic lupus erythematosus).
8. Active seizure disorder within the last 2 years. Subjects who are on stable medication and have not experienced seizures for more than 2 years may be enrolled.
9. Clinical evidence of chronic cardiac disease (eg, coronary artery disease, congestive heart failure, uncontrolled hypertension, significant arrhythmia).
10. Clinical evidence of chronic pulmonary disease (eg, chronic obstructive pulmonary disease) associated with functional impairment.
11. History of organ transplant other than cornea and hair transplant.
12. History of known clinically significant hemoglobinopathy (eg, thallasemia, sickle cell anemia). Subjects who have sickle cell trait or thallasemia minor with normal Hb values may be enrolled in the study.
13. History of known coagulopathy including hemophilia.
14. History of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
15. 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 or in situ carcinoma of the uterine cervix).
16. A history of any other medical disease or condition that would make the subject (in the opinion of the investigator) unsuitable for the study.
17. Drug or alcohol addiction within the last 6 months. Subjects who have a documented addiction?free period of at least 6 months and in the clinical judgment of the investigator are not at risk for relapse may be enrolled in the study. Subjects in a supervised methadone treatment program may be enrolled in the study.
18. 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.
19. Requirement for chronic systemic corticosteroids (prednisone equivalent of > 10 mg/day).
20. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 28 days prior to Day 0. Subjects being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for mild, localized recurrent herpes simplex infection may be enrolled in the study.
21. Received concomitant systemic antibiotics or antifungal for the treatment of active infection within 28 days prior to Day 0. Subjects treated with oral antibiotics for acne may be enrolled in the study.
22. Received silymarin (milk thistle) or glycyrrhizin within 28 days prior to Day 0.
23. Received any experimental agent within 28 days prior to Day 0. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Sustained virologic response (SVR), defined as undetectable HCV RNA (< 10 IU/mL) at Week 48. |
|
| 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 | 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) | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 44 |
| 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 |
|
| 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 | 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 |
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