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 | PT |
E.1.2 | Classification code | 10008909 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
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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 whether the proportion of patients who achieve cEVR (by Limit of Quantitation, LOQ, i.e. HCV RNA < 25 IU/mL) after 12 weeks of triple therapy with DEB025 600 mg/day combined with peg-IFNα2a 180 μg 1x/week and RBV 1000/1200 mg/day is higher compared to the proportion of patients who achieve cEVR after 12 weeks of placebo matching DEB025 treatment plus SOC therapy consisting of peg-IFNα2a 180 μg 1x/week + RBV 1000/1200 mg/day in chronic hepatitis C GT1 patients with previous non-response to SOC. |
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E.2.2 | Secondary objectives of the trial |
The key secondary efficacy variable is the proportion of patients who achieve SVR24, defined as HCV RNA < LOQ at the end of 24 week post-treatment follow-up. The key secondary comparison is between active DEB025 600 mg plus SOC treatment group (A) and DEB025 600 mg placebo plus SOC control group (C) in terms of proportion of patients achieving SVR24. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients eligible for inclusion in this study have to fulfill all of the following criteria: 2. Written informed consent must be obtained before any assessment is performed. 3. Males or females aged ≥18 and ≤ 65 years; 4. BMI between ≥ 18 and ≤ 36 kg/m2; 5. HBsAg negative and HIV negative; 6. Chronic hepatitis C viral infection on record and diagnosed by two tests performed at an interval of at least 6 months (the initial diagnosis can be based on positive HCV antibodies or quantitative or qualitative HCV RNA measurement). Furthermore, chronicity needs to be confirmed by a positive HCV RNA test, i.e. qPCR (quantitative polymerase chain reaction); thus the 2nd test may be performed at screening; 7. Plasma HCV RNA level lower limit ≥ 10000 IU/ml assessed by qPCR (quantitative polymerase chain reaction) or equivalent at screening; no upper limit; 8. HCV genotype 1; 9. Previous non-responders to SOC (with peg-IFNa 2a or 2b and RBV) after full dose treatment for at least 12 weeks with detectable HCV RNA at the end of treatment. A minimum of 3 months must have elapsed since the patient`s last treatment when the patient qualified as a non-responder and recruitment into this study. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Treatment with any anti-HCV drug (whether approved or investigational) within 3 months prior to screening in the current trial. 2. Ongoing or recent use of any other medication (including over the counter medication and herbal products) within 2 weeks before study start or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome 450 3A, substrates of cytochrome 450 3A, substrates of P-gp, or substrates/inhibitors of OATPs, MRP2 or BSEP, and are mentioned in the list of unauthorized medications. 3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. Any medical contraindication to treatment with IFN and/or RBV. 4. Patients with evidence of cirrhosis at the time of screening. Confirmation of non-cirrhotic status of a patient needs to be obtained from a liver biopsy result within the past 24 months or by transient elastography (within 6 months prior to screening). Any other means for detection of cirrhosis (e.g. no evidence of portal hypertension) should also be considered to exclude cirrhosis. 5. Active or suspected cancer, or a history of malignancy where the risk of recurrence is ≥ 20% within 2 years. Lack of exclusion of hepatocellular carcinoma by any imaging technique within 6 weeks prior to screening and serum Alpha-fetoprotein (AFP) > 100 ng/mL. 6. History of clinical evidence of chronic cardiac disease or ECG with clinically significant abnormalities, such as QTc > 450 msec for males and > 470 msec for females (Fredericia correction) at screening or baseline. Angina pectoris or ischaemic heart disease requiring current medical intervention. 7. Women of child-bearing potential (WOCBP), 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 post-menopausal: 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 passed 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 (any marketed contraceptive agent that includes an estrogen and/or a progestational agent) • Intrauterine device (copper or hormonal) • Diaphragm with spermicide • Sponge 8. 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. 9. 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. 10. HCV genotype different from genotype 1 or co-infection of GT1 plus another HCV genotyp PLS SEE PROTOCOL |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate whether the proportion of patients who achieve cEVR (by Limit of Quantitation, LOQ, i.e. HCV RNA < 25 IU/mL) after 12 weeks. |
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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 | 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 6 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |