E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic liver insufficiency |
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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 | 10024667 |
E.1.2 | Term | Liver cirrhosis |
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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 | 10024670 |
E.1.2 | Term | Liver disorder |
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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 determine the maximum tolerated dose of expanded autologous cells derived from a subset of CD34+ stem cells when infused into either the hepatic artery or the portal vein. The trial will also seek to determine clinical improvement or deterioration by measurement of clinical parameters such as liver function tests. |
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E.2.2 | Secondary objectives of the trial |
To assess improvement in liver function as measured by serological and biochemical analysis and determine whether there are any symptomatic improvements as reported by the patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients aged from 18 to 75 years of age with documented evidence of chronic liver insufficiency due to chronic alcohol abuse, viral hepatitis, blood clotting disorders, and/or autoimmune disease. Patients with severe renal, cardiac or other diseases providing these are not immediately life threatening Abnormal serum albumin and/or bilirubin and/or prothrombin time Patients who are unlikely to receive a liver transplant WHO performance score of less than 2 with a life expectancy of at least 3 months Able to give written consent Women of childbearing potential may be included, but must use a reliable and appropriate contraceptive method
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E.4 | Principal exclusion criteria |
Patients below the age of 18 or above the age of 75 years Pregnant or lactating women Patients with recent recurrent GI bleeding or spontaneous bacterial peritonitis Patients with HIV or other life threatening infection Patients with a history of drug abuse Patients unable to give written consent Patients with a history of hypersensitivity to G-CSF Patients who have been included in any other clinical trial within the previous month
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the safety of ascending doses of autologous adult stem cells when introduced into either the hepatic artery or the portal vein and to determine the maximum tolerated dose of stem cells. The route of delivery is determined by radiological opinion. |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
prospective dose escalation and clinical efficacy study |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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All patients will be assessed 4 weeks after coming off study (week 12), whether from completion of protocol or early withdrawal for whatever reason. They will also be monitored in the clinic for the remainder of their life.
Patients who are withdrawn due to issues of toxicity will be followed until the adverse event is resolved or the outcome is known. Patients will then be followed-up for four weeks after resolution and thereafter for life in the clinic.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |