E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Liver Failure
Subgroups of patients with indications falling under ICD classification codes:K70.4, K71, K72, K75, K76, K77
|
|
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 | 10049844 |
E.1.2 | Term | Acute liver failure |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the trial is to investigate the efficacy and safety of multiple applications of liver cell suspension in patients with ALF.
The primary variable is the survival rate at 8 weeks after randomization. |
|
E.2.2 | Secondary objectives of the trial |
Efficacy: • Survival rate at 6 months after randomization • Hepatic encephalopathy score • Karnofsky -Index at week 2, 4 and 8 • Laboratory parameters I: INR, AFP, albumin, bilirubin, liver enzymes (GOT, GPT, GLDH, GGT, AP) • Laboratory parameter IA: Factor V • Pharmacoeconomic evaluation (duration of initial hospitalization, number and duration of hospitalizations after initial admission, total days at ICU, concomitant medical interventions including blood substitution therapy) • Assessment of Quality of Life (QoL)
Safety: • All adverse events and serious adverse events • Infection events • Laboratory parameter IB: blood levels of immunosuppression • Laboratory parameters II: CRP, lactate, creatinine, haematology (haemoglobin, hematocrit, erythrocytes, leucocytes including differential count, platelets) • Vital signs |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18 years and above • Patient suffering from ALF defined as - Hepatic encephalopathy grade >= 1 - INR > 2,0 - GOT, GPT and GLDH increased by at least 3 times UNL in absence of signs of chronic liver disease ( = no fibrosis or cirrhosis) • Patient expected to be not eligible for orthotopic liver transplantation • Written informed consent before enrolment |
|
E.4 | Principal exclusion criteria |
- Acute liver insufficiency in presence of symptomatic chronic liver disease (fibrosis or cirrhosis of the liver) - Acute liver failure in case of transplant primary non-function - Acute liver failure due to Budd-Chiari-Syndrome or venoocclusive disease - Thrombosis of portal vein or persisting impairment of anterograde portal blood flow - Allergic disposition for antibiotics used during manufacturing of liver cell transplants - Encephalopathy other than hepatic - Massive ascites (> 3 l) - Malignancies except basaliomes - Clinically manifest acquired immunodeficiency syndrome (AIDS) - Contraindication to immunosuppressive therapy (e.g. severe acute bacterial, viral or fungal infection, intolerability to immune suppression) - Treatment with extracorporeal liver assist devices (e.g. MARS, - Prometheus, HepatAssist) - Pregnancy or lactation - Participation in another clinical trial within the last 30 days
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Survival rate at 8 weeks after randomization |
|
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 | 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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
control group: without catheterization, without cell application, without immunosuppression |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
control group: without catheterization, without cell application, without immunosuppression |
|
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 | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
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
| |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |