E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
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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 |
To evaluate the safety and tolerability of up to four doses of alb-IFN Q4w (900 µg, 1200 µg, 1500 µg and possibly 1800 µg) plus daily RBV in IFNα naïve patients with genotype 2/3 CHC. |
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E.2.2 | Secondary objectives of the trial |
To characterize the efficacy of up to four 4 doses of alb-IFN Q4w (900 µg, 1200 µg,1500 µg and 1800 µg) plus daily RBV as measured by: • Sustained Virologic Response (SVR), defined as undetectable HCV RNA (i.e., HCV RNA < limit of detection [LOD]; 15 IU/mL) at 24 weeks post-treatment. • Virologic Response below LOQ (43 IU/mL) at Treatment Week 12 (TW12). • Rapid Virologic Response at Treatment Week 4 (RVR4), defined as HCV RNA < limit of quantification (LOQ [43 IU/mL]) • Early Virologic Response at Treatment Week 12 (EVR12), defined as a ≥ 2 log10 reduction or HCV RNA < LOQ (43 IU/mL) • End of Treatment Response (ETR), defined as undetectable HCV RNA (< LOD [15 IU/mL]) at Week 24 or the visit closest to the date of last dose of either interferon or RBV within ±27 days of window • Change from baseline in log10 HCV RNA at Weeks 4, and 12 • Time to HCV RNA < LOD (15 IU/mL)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age of 18 years or older 2. Clinical diagnosis of chronic hepatitis C, including detectable HCV RNA at the time of screening 3. Infection with HCV genotype 2 or 3. Subjects infected with mixed HCV genotypes (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. 4. No previous IFNα-based therapy 5. Ability to provide written informed consent in accordance with institutional and regulatory guidelines; willing and able to comply with study protocol procedures
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E.4 | Principal exclusion criteria |
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS (1) they meet the following definition of postmenopausal: 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: and estradiol <20 pg/mL], or (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy [in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment], or (3) agree to use at least two reliable forms of effective contraception during treatment and during the 7-month post-treatment follow-up period. One method is the male’s use of a condom with spermicide. The other must be one of the following: • Surgical sterilization (e.g., bilateral tubal ligation) • Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent • Intrauterine device (copper or hormonal) • Diaphragm with spermicide • Sponge - Fertile males, defined as all males physiologically capable of conceiving offspring may be enrolled in this study if the patient agrees to use a condom with spermicide and his female partner agrees to use one or more of the acceptable methods of contraception listed above from the date of screening until 7 months after their last dose of RBV - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). Men whose female partners are pregnant or contemplating pregnancy - History or current evidence of decompensated liver disease (ascites, variceal bleeding, hepatic encephalopathy, or other signs of progressive portal hypertension or progressive hepatic insufficiency [prothrombin INR > 1.4; serum albumin < 3.5 g/dl]) - Coinfection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) - History of moderate, severe or uncontrolled psychiatric disease (e.g., depression [including a history of hospitalization or prior suicidal attempt], bipolar disease, schizophrenia, or personality disorder]). Patients 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 [HADS-D] score of ≤ 8) of the patient’s affective status supports that the patient is clinically stable. Patients with a HADS-D 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 patients, and must review the patient’s affective status according to the plan at every visit. Patients with a HADS anxiety subscale (HADS-A) score of > 8 may be enrolled at the investigator’s discretion. - History of seizure disorder - History or clinical evidence of chronic cardiac disease; ECG with clinically significant abnormality. The Long QT syndrome or QTc >450 msec for males and > 470 msec for females at screening or baseline. - Clinical evidence of preexisting interstitial lung disease - Clinical evidence of severe lung disease (e.g., chronic restrictive pulmonary disease, chronic obstructive pulmonary disease; please refer to Post-text supplement 1) - Clinically significant findings on fundoscopic or retinal examination at screening based on the investigator’s clinical judgment or by ophthalmologist/optometrist for patients with diabetes - History of clinically significant hemoglobinopathy; patients who have sickle cell trait or thalassemia minor with normal hemoglobin values may be enrolled - Have a clinically significant laboratory abnormality at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to evaluate the safety and tolerability of alb-IFN Q4w regimens plus daily RBV in IFNα naïve patients with genotype 2/3 CHC. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | 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
| 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 | 9 |
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 | 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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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 | |
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 | 1 |