E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In-vivo diagnostic marker for liver dysfunction. |
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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 | 10009213 |
E.1.2 | Term | Cirrhosis of liver |
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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 |
Quantification of liver function by NRL972-pharmacokinetics before, during and after standard treatment of chronic hepatitis B and C |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability of repeated single doses of 2 mg NRL972 before, during and after standard treatment of chronic hepatitis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Chronic hepatitis B Adult, male or female, age ≥ 18 years and < 65 years Body weight (BW) : 45 - 110 kg Body mass index (BMI) : 18 – 30 kg.m-2 HBV Serology: HBsAg+ for ≥ 6 months (at the time of application for treatment) Serum ALT ≥ 1.5 times ULN ≥ 6 months (at the time of application for treatment) Positive liver biopsy within 24 months before screening visit Positive biopsy with signs of active disease (any level of activity by Knodell, METAVIR or ISHAK) HBV DNA counts determined by quantitative PCR: ≥ 20,000 IU/mL ALT < 10 times ULN HIV-Ab negative Non-cirrhotic liver disease on histology Not having been treated for chronic hepatitis previously ("de novo" i.e. "naïve") Eligible for treatment of chronic hepatitis in accordance with the national consensus guidelines pertinent to the country and site of conduct of the trial Willing and able to provide informed consent
Chronic hepatitis C Adult, male or female, age ≥ 18 years and < 65 years Body weight (BW) : 45 - 110 kg Body mass index (BMI) : 18 – 30 kg.m-2 HCV-Ab+ for ≥ 6 months (at the time of application for treatment) HCV RNA counts > 10,000 U/L by quantitative PCR assay within the last 6 months (at the time of application for treatment) Positive liver biopsy within 24 months before application for treatment Positive biopsy with signs of fibrotic disease (levels of fibrosis METAVIR ≥ F1 or ISHAK ≥ F2) ALT < 10 times ULN HIV-Ab negative Non-cirrhotic liver disease (on histology histology) Not having been treated for chronic hepatitis previously ("de novo" i.e. "naïve") Eligible for treatment of chronic hepatitis in accordance with the national consensus guidelines pertinent to the country and site of conduct of the trial Willing and able to provide informed consent
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E.4 | Principal exclusion criteria |
A. General criteria Previous participation in the trial Participation in any other clinical trial within 30 days of entry to this protocol Treatment with any investigational drug within 30 days of entry to this protocol Non-response to previous treatment for chronic hepatitis Relapse after previous treatment for chronic hepatitis Any other known cause of liver disease other than chronic hepatitis B and/or C, including but not limited to hepatitis D, haemochromatosis, alpha1-antitrypsin deficiency, Wilson’s disease, autoimmune hepatitis, drug-related liver disease Evidence of advanced liver disease, such as history or presence of ascites, bleeding varices, encephalopathy Patients with organ transplants Hypersensitivity to prospective standard treatment Any relevant co-morbidity, for instance, but not limited to: - Limiting uncompensated psychiatric condition (e.g. severe depression, or a history of severe psychiatric disorder) - CNS trauma or seizure disorder requiring medication - Significant cardiovascular dysfunction within the past 6 months (e.g. angina, congestive cardiac failure, recent myocardial infarction, severe hypertension or significant arrhythmia) - Patients with an ECG showing clinically significant abnormalities - Poorly controlled diabetes mellitus - Patients on haemodialysis Daily use of > 40 g alcohol Positive alcohol test at SCR-visit Evidence or suspicion of social drug abuse Positive drug test at SCR-visit Use of prohibited medication Suspicion or evidence that the subject is not trustworthy and reliable Suspicion or evidence that the subject is not able to make a free consent or to under-stand the information in this regard
B. Exclusion criteria related to the medicaiton used for the standard treatment of chronic hepatitis: Relevant clinical laboratory test abnormalities, for instance, but not limited to: - Haemoglobin (Hgb) <11 g dL–1 for women and <13 g dL–1 for men - White Blood Cell count (WBC) < 3,000 109/mL - Granulocyte count < 1,500 109/mL - Lymphocyte count < 500 109/mL - Platelets < 75,000 109/mL - Prothrombin time – INR > 1.4 - Bilirubin > 25 mol/L (except in functional hyperbilirubinaemia) - Albumin < 35 g/L - Serum creatinine > 133 mol/L - Fasting blood glucose > 7.4 mmol/L for non-diabetic patients - HbA1c > 7% for diabetic patients - Positive auto-immune antibodies - TSH outside the normal range (for patients intended for interferon) Relevant co-morbidity, for instance, but not limited to: - Limiting uncompensated chronic pulmonary disease (e.g. chronic obstructive pulmonary disease) - Any medical condition requiring, or likely to require during the course of the study, - chronic systemic administration of steroids - Gout – (for patients intended for interferon) - Immunologically mediated disease (e.g. inflammatory bowel disease, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, cryoglobulinaemia with vasculitis) – (for patients intended for interferon) Patients with clinically significant retinal abnormalities – (for patients intended for interferon)
C. Criteria applicable to all female subjects: Positive pregnancy test Lactating Not using medically appropriate contraception and/or not willing to maintain such contraception during the treatment of chronic hepatitis and up to 6 months thereafter
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics of NRL972 in terms of the C(30):C(10)-ratio, clearance (CL & CL/BW), and apparent terminal disposition half-life (t1/2) and urinary excretion of NRL972 |
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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 | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | No |
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 | 9 |
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 | 9 |