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 | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Intensive sample collections for pharmacokinetics and HCV RNA levels will be taken in a sub-group of patients (n=20) per treatment group. In this sub group, blood samples will be obtained at 13 time-points. For any PK sampling scheduled on the same day as alb-IFN or PEG-IFN injection, PK sample collection will be obtained prior to the injection. For all remaining patients, sparse PK sampling will be conducted at the following 8 timepoints: Day 1, 15 (Week 2), 29 (Week 4), 43 (Week 6), 57 (Week 8), 85 (Week 12), 113 (Week 16) and 169 (Week 24). For any PK sampling scheduled on the same day as alb-IFN or Pegays injection, PK sample collection will be obtained prior to the injection. |
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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]) - Other forms of liver disease (e.g., alcoholic, autoimmune, biliary, or Wilson’s). However, Gilbert’s or Dubin-Johnson syndromes will not exclude patients. - 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 - Diagnosis of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin - Organ transplantation other than cornea or hair transplant - 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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Health-related Quality of Life |
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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 | 5 |
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 |
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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 |