Allogeneic ABCB5-positive Stem Cells for Treatment of Acute-on-Chronic Liver Failure

NCT03860155 | Terminated Phase 1 DMC

• 1 other identifier: allo-APZ2-ACLF-II-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 5

Brief Summary

This is an interventional, single arm, multicenter, phase I/IIa clinical trial. The study objective is to investigate the efficacy and safety of three i.v. doses of the investigational medicinal product (IMP) allo-APZ2-ACLF for the treatment of acute-on-chronic liver failure (ACLF). The allogeneic IMP allo-APZ2-ACLF contains skin-derived ABCB5-positive mesenchymal stem cells isolated from skin tissue of healthy donors and stored in a donor cell bank.

Conditions

Acute-On-Chronic Liver Failure

Keywords

Acute-on-Chronic Liver Failure; ACLF; ABCB5; ATP Binding Cassette Subfamily B Member 5; allogeneic; mesenchymal stem cells; advanced therapy medicinal product; somatic cell therapy; phase I/IIa

Outcome Measures

Primary Outcomes (2)

• Change of Model for End-Stage Liver Disease (MELD) score at Week 24 or last available post-baseline measurement if the Week 24 score is missing.

  Model for End-Stage Liver Disease (MELD) score for assessing the severity of chronic liver disease is measured as absolute change to baseline score at Week 24 or last available post-baseline measurement if the Week 24 score is missing.

  Week 24, or last available post-baseline measurement of Days 5 (±1) or 13 (±1) or Weeks 3, 4, 8, 12, 16 or 20 if the Week 24 measurement is missing [LOCF].

• Assessment of adverse event (AE) occurrence

  All AEs occurring during the clinical trial will be registered, documented and evaluated.

  Between Screening and Month 24

Secondary Outcomes (25)

• Change of MELD score at Weeks 3, 4, 8, 12, 16 and 20

  Weeks 3, 4, 8, 12, 16 and 20

• Change of Child-Pugh-Score at Weeks 3, 4, 8, 12, 16, 20 and 24

  Weeks 3, 4, 8, 12, 16, 20 and 24

• Change of CLIF-C ACLF score at Weeks 3, 4, 8, 12, 16, 20 and 24

  Weeks 3, 4, 8, 12, 16, 20 and 24

• Overall survival time until Week 24

  Between Screening and Week 24

• Complications of ACLF (hepatorenal syndrome [HRS], variceal bleeding, ascites, hepatic encephalopathy [HE], spontaneous bacterial peritonitis [SBP])

  Between Screening and Week 24

Study Arms (1)

allo-APZ2-ACLF

EXPERIMENTAL

Application of IMP into peripheral vein (arm) by use of a perfusor.

Biological: allo-APZ2-ACLF

Interventions

allo-APZ2-ACLF BIOLOGICAL

Administration of 2 x 10e6 allogeneic ABCB5-positive stem cells/kg bodyweight, each at Day 0, Day 5 (±1) and Day 13 (±1) into peripheral vein (arm) intravenously with a flow rate of 1-2 ml/min. Infusion of the product via a central venous catheter (CVC), a Port-a-Cath (Port) or a similar catheter is also possible. Allo-APZ2-ACLF will be in a concentration of 1 x 10e7 cells/mL in Human Serum Albumin/Ringer-Lactate/Glucose (HRG)-solution.

Also known as: Skin-derived ABCB5-positive mesenchymal stem cells

allo-APZ2-ACLF

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, aged 20 to 75 years;
• Diagnosed ACLF of grade 2 or 3 according to EASL-CLIF definition;
• Patients are not eligible for liver transplant (confirmed by transplantation board);
• Histology result of liver biopsy not older than 4 weeks before screening;
• Women of childbearing potential must have a negative blood pregnancy test at screening;
• Women of childbearing potential and fertile men, and their partners must be willing to use highly effective contraceptive methods during the course of the clinical trial;
• Written informed consent from patient, legal or authorized representative or a confirmation of justification of trial participation by an independent medical consultant. In case of confirmation by the independent medical consultant, a deferred informed consent from patient, legal or authorized representative has to be given.

You may not qualify if:

• Patients without cirrhosis;
• Patients with ACLF grade 1 according to EASL-CLIF definition;
• Patient with septic shock;
• Patients with known hepatopulmonal syndrome (HPS);
• Patients with known pulmonary embolism that needs anticoagulative treatment;
• Patients with pre-existing lung disease with necessity of respiratory support;
• Active malignancy or history of malignancy within 5 years prior to trial entry;
• Known infection with human immunodeficiency virus (HIV˗1, HIV-2);
• Any known allergies to components of the IMP;
• Current or previous (within 30 days of enrolment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
• Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
• Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment;
• Pregnant or nursing women;
• Employees of the sponsor, or employees or relatives of the investigator.

Sponsors & Collaborators

• RHEACELL GmbH & Co. KG: lead
• FGK Clinical Research GmbH: collaborator
• Ticeba GmbH: collaborator

Study Sites (5)

Universitätsklinikum Carl-Gustav-Carus an der TU Dresden, Medizinische Klinik I

Dresden, 01307, Germany

Location

Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Medizinisches Forschungszentrum

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt, Medizinische Klinik 1, Sektion Translationale Hepatologie

Frankfurt, 60590, Germany

Location

Universitätsklinikum Magdeburg A.ö.R., Medizinische Fakultät der Otto-von-Guericke-Universität

Magdeburg, 39120, Germany

Location

Medizinische Fakultät Mannheim der Universität Heidelberg, II. Medizinische Klinik

Mannheim, 68167, Germany

Location

Related Publications (1)

• Kerstan A, Niebergall-Roth E, Esterlechner J, Schroder HM, Gasser M, Waaga-Gasser AM, Goebeler M, Rak K, Schrufer P, Endres S, Hagenbusch P, Kraft K, Dieter K, Ballikaya S, Stemler N, Sadeghi S, Tappenbeck N, Murphy GF, Orgill DP, Frank NY, Ganss C, Scharffetter-Kochanek K, Frank MH, Kluth MA. Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data. Cytotherapy. 2021 Feb;23(2):165-175. doi: 10.1016/j.jcyt.2020.08.012. Epub 2020 Oct 1.

  PMID: 33011075 DERIVED

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Matthias Ebert, Prof. Dr.

  Med. Fakultät Mannheim der Universität Heidelberg, II. Med. Klinik, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: March 1, 2019
• Study Start: March 22, 2019
• Primary Completion: March 26, 2021
• Study Completion: March 26, 2021
• Last Updated: November 17, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)