A Study of ADR-001 in Patients With Liver Cirrhosis

A Phase 1/2 Study of ADR-001 in Patients With Liver Cirrhosis

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.

Study Overview

• Status: Completed
• Conditions: Decompensated Liver Cirrhosis
• Intervention / Treatment: Biological: Mesenchymal stem cell

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rohto Pharmaceutical Co., Ltd.; Phone Number: +81-3-6823-6014; Email: adr-001@rohto.co.jp

Study Locations

• Japan
  • Niigata, Japan, 951-8510
    • Niigata University Medical & Dental Hospital
  • Tokyo, Japan, 173-8610
    • Nihon University Itabashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stem cell; Phase 1 Dose escalation : low Mid High Single administalation of ADR-001 Phase 2 The recommended dose of ADR-001	Biological: Mesenchymal 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of ADR-001 including the incidence of adverse events (Phase 1)	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.	24 weeks
Improvement rate of Child-Pugh score (Phase 2)	Improvement rate of Child-Pugh score from the baseline will be evaluated.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of liver function evaluated by Child-Pugh score (Phase 1)	Change of liver function from the baseline will be evaluated by Child-Pugh score.	24 weeks
Improvement rate of Child-Pugh score (Phase 1)	Improvement rate of Child-Pugh score from the baseline will be evaluated.	24 weeks
Improvement rate of Child-Pugh grade (Phase 1)	Improvement rate of Child-Pugh grade from the baseline will be evaluated.	24 weeks
Change of liver function evaluated by Child-Pugh score (Phase 2)	Change of liver function from the baseline will be evaluated by Child-Pugh score.	24 weeks
Improvement rate of Child-Pugh grade (Phase 2)	Improvement rate of Child-Pugh grade from the baseline will be evaluated.	24 weeks
Safety profile of ADR-001 including the incidence of adverse events (Phase 2)	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.	24 weeks

Collaborators and Investigators

• Sponsor: Rohto Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Shuji Terai, MD, Niigata University Medical & Dental Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2017
• Primary Completion (Actual): April 13, 2023
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: ADR-001-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No