Decompensated Liver Cirrhosis
Conditions
Brief summary
This is a first-in-human Phase1/2 study of ADR-001, adipose-derived mesenchymal stem cells (AD-MSCs). The safety and preliminary efficacy are evaluated in Phase 1 in patients with liver cirrhosis caused by Hepatitis C or Nonalcoholic Steatohepatitis and a recommended Phase 2 dose is determined by the evaluation. The exploratory efficacy and safety are investigated against the same target population in Phase 2.
Detailed description
Patients with decompensated liver cirrhosis (Child-Pugh score; Grade B) caused by Hepatitis C or Nonalcoholic Steatohepatitis are enrolled to the study. In Phase 1, one of 3 doses of AD-MSCs is administered by 1 hour single intravenous infusion. Patients are hospitalized for 1 week and a recommended dose for Phase 2 is determined by the evaluation of the safety and efficacy. In Phase 2, patients with the same disease criteria are enrolled and dosed to investigate the exploratory efficacy and safety. The safety and efficacy are evaluated until 24 weeks after dosing both in Phase 1 and Phase 2.
Interventions
BIOLOGICALMesenchymal stem cell
Phase1 The dose of AD-MSCs are escalated from low to mid and high step by step. Each administration is one time via intravenous infusion for one hour. Phase2 The recommended dose of ADR-001 is administrated once a week 4 times. The administration route and time is same method with Phase 1.
Sponsors
Rohto Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 20 years of age * Chronic hepatitis C or nonalcoholic steatohepatitis(NASH) * Child-Pugh grade B liver cirrhosis * ECOG Performance Status ≤ 2
Exclusion criteria
* Liver cirrhosis patients other than hepatitis C or NASH * Malignant neoplasm (except hepatocellular carcinoma patients without recurrence more than 2 years) * History of venous thrombosis or pulmonary embolism * Serum creatinine ≥ 2 mg/dL or T-Bil ≥ 5.0 mg/dL * Infection with hepatitis B, HIV, ATLV-1 or parvovirus B19 * Patients experienced transplantation or cell therapy * Pregnancy or positive on pregnancy test * Complications of significant heart disease, kidney disorder, or respiratory disease * Drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile of ADR-001 including the incidence of adverse events (Phase 1) | 24 weeks | Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations. |
| Improvement rate of Child-Pugh score (Phase 2) | 24 weeks | Improvement rate of Child-Pugh score from the baseline will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement rate of Child-Pugh grade (Phase 1) | 24 weeks | Improvement rate of Child-Pugh grade from the baseline will be evaluated. |
| Change of liver function evaluated by Child-Pugh score (Phase 2) | 24 weeks | Change of liver function from the baseline will be evaluated by Child-Pugh score. |
| Change of liver function evaluated by Child-Pugh score (Phase 1) | 24 weeks | Change of liver function from the baseline will be evaluated by Child-Pugh score. |
| Safety profile of ADR-001 including the incidence of adverse events (Phase 2) | 24 weeks | Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations. |
| Improvement rate of Child-Pugh grade (Phase 2) | 24 weeks | Improvement rate of Child-Pugh grade from the baseline will be evaluated. |
| Improvement rate of Child-Pugh score (Phase 1) | 24 weeks | Improvement rate of Child-Pugh score from the baseline will be evaluated. |
Countries
Japan
Outcome results
None listed